Indazole-containing macrocyclic compounds and uses thereof

Abstract

The present disclosure relates to indazole-containing macrocyclic compounds, pharmaceutical compositions containing macrocyclic compounds, and methods of using macrocyclic compounds in the treatment of diseases such as cancer.

Description

[0001] Related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 350,309, filed on June 8, 2022, U.S. Provisional Application No. 63 / 350,310, filed on June 8, 2022, and U.S. Provisional Application No. 63 / 503,879, filed on May 23, 2023, the entire disclosures of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to indazole-containing macrocyclic compounds, pharmaceutical compositions containing the macrocyclic compounds, and methods of using the macrocyclic compounds to treat diseases such as cancer. Background Art

[0004] Protein kinases are tightly regulated signal transduction proteins that coordinate the activation of signal cascades by phosphorylating target proteins in response to extracellular and intracellular stimuli. The human genome encodes approximately 518 protein kinases (Manning G et al., The protein kinase complement of the human genome. Science. 2002, 298: 1912-34). Dysregulation of kinase activity is associated with many diseases, including cancer and cardiovascular disease, degenerative diseases, immune diseases, infectious diseases, inflammatory diseases, and metabolic diseases (Levitzki, A., Protein kinase inhibitors as atherapeutic modality. Acc. Chem. Res. 2003, 36: 462-469). The molecular basis for various diseases includes kinase gain- and loss-of-function mutations, gene amplification and deletion, splicing changes, and translocations (Wilson LJ et al., New Perspectives, Opportunities, and Challenges in Exploring the Human Protein Kinome. Cancer Res. 2018, 78:15-29). The important role of kinases in cancer and other diseases makes them attractive targets for drug discovery, with 62 small molecule kinase inhibitors approved and 55 used in targeted cancer therapies (Roskoski R Jr., Properties of FDA-approved Small Molecule Protein Kinase Inhibitors: A 2021 Update. Pharmacol Res 2021, 165:105463). Although kinase inhibitors have achieved great success in cancer targeted therapy, the development of treatment resistance remains a challenge faced by small molecule kinase inhibitors.Acquired secondary mutations within the kinase domain during treatment often lead to therapeutic resistance to kinase inhibitors (Pottier C et al., Tyrosine Kinase Inhibitors in Cancer: Breakthrough and Challenges of Targeted Therapy. Cancers (Basel), 2020, 12: 731). Resistance can also arise from a subpopulation of resistant / persister cells that survive treatment. Different processes contribute to the emergence of resistant persister cells, including pathway rebound via the release of negative feedback loops, transcriptional rewiring mediated by chromatin remodeling, and autocrine / paracrine communication in tumor cells and within the tumor microenvironment (Swayden M et al., Tolerant / Persister Cancer Cells and the Path to Resistance to Targeted Therapy. Cells 2020, 9, 2601). Therefore, there is a need to invent kinase inhibitors that can not only target kinase oncogenic drivers to overcome the most common resistance mutations, but also tolerate surviving cancer cells to overcome resistance, achieving better efficacy and longer-term disease control.

[0005] Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide (World Health Organization. Cancer Fact Sheet 2017). Activating EGFR mutations have been reported in approximately 10% to 15% of adenocarcinoma cases in white patients and 50% of adenocarcinoma cases in Asian patients (Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res 2015;4:36-54). The two most common EGFR alterations found in NSCLC tumors are a short in-frame deletion (del19) in exon 19 of the EGFR gene and a single missense mutation, L858R, in exon 21 (Konduri K et al., EGFR Fusions as Novel Therapeutic Targets in Lung Cancer. Cancer Discovery 2016, 6:601-11).

[0006] The first-generation reversible EGFR inhibitors, erlotinib and gefitinib, are superior to chemotherapy in patients with advanced EGFR mutation-positive (Del19 or L858R) NSCLC and have been used as first-line standard of care in this setting. However, over time, most patients develop resistance to gefitinib or erlotinib, with 50% to 70% of tumors harboring the EGFR T790M gatekeeper gene mutation (Sequist LV et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011;3:75ra26). The second-generation EGFR inhibitors afatinib and dacomitinib are covalent, irreversible EGFR inhibitors that also inhibit HER2 and ERB4 of the ERB family (Li D et al., BIBW2992, an irreversible EGFR / HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008;27:4702-11; Ou SH, Soo RA, Dacomitinib in lung cancer: a “lost generation” EGFR tyrosine-kinase inhibitor from a bygone era? Drug Des Devel Ther 2015;9:5641-53).

[0007] Although afatinib and dacomitinib are more potent EGFR inhibitors compared with gefitinib and erlotinib and are approved as first-line therapies for advanced EGFR mutation-positive (Del19 or L858R) NSCLC with longer progression-free survival (PFS), EGFR T790M has emerged with afatinib treatment (Tanaka K, et al., Acquisition of the T790M resistance mutation during afatinib treatment in EGFR tyrosine kinase inhibitor-naive patients with non-small cell lung cancer harboring EGFR mutations. Onco-target 2017;8:68123-30). EGFR T790M confers resistance to dacomitinib in in vitro studies (Kobayashi Y, et al., EGFR T790M and C797S mutations as mechanisms of acquired resistance to dacomitinib. J Thorac Oncol 2018;13:727-31). Osimertinib, a third-generation EGFR inhibitor, is also an irreversible inhibitor that targets both EGFR activating mutations (Del19 and L858R) and the T790M resistance double mutation and has superior selectivity to wild-type EGFR (Finlay MR et al., Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild-type form of the receptor. J Med Chem 2014;57:8249-67).Osimertinib was first approved for patients with metastatic EGFR T790M mutation-positive NSCLC after failure of first-line EGFR inhibitors and was subsequently approved for first-line treatment of patients with EGFR mutation-positive NSCLC following the phase III FLAURA trial, a head-to-head trial compared with erlotinib or gefitinib (Soria JC, et al. Osimertinibin untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018;378:113-25). The mutation C797S at the residue on the EGFR covalently bound by the irreversible EGFR inhibitor osimertinib has been detected in osimertinib-resistant patients (Ramalingam SS et al., Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study. Presented at ESMO 2018).

[0008] Therefore, there is a need to develop a new generation of reversible EGFR inhibitors that are effective against oncogenic driver EGFR mutations, such as L858R, Del19, Δ746-750, Δ746-750 / T790M, Δ746-750 / C979S, L858R / T790M, Del19 / T790M, L858R / C979S, Del19 / C979S, L858R / T790M / C979S and Δ746-750 / T790M / C979S, as well as other emerging and established resistance mutations, while maintaining good selectivity against wild-type EGFR.

[0009] Proviral integration of Moloney murine leukemia virus (PIM) kinases is an oncogenic serine / threonine kinase that phosphorylates numerous substrates that regulate several hallmarks of cancer, including tumor metabolism, survival, metastasis, immune evasion, and inflammation (Toth RK, Warfel NA, Targeting PIM Kinases to Overcome Therapeutic Resistance in Cancer. Mol Cancer Ther. 2021, 20(1):3-10). PIM kinases interact with many major oncogenic players, including stabilization of p53, synergistic effects with c-Myc, and significant parallel signaling with PI3K / Akt. Aberrant PIM kinase activity plays an important role in resistance mechanisms to chemotherapy, radiotherapy, anti-angiogenic therapy, and targeted therapies, providing a rationale for combination targeted therapy strategies for more durable patient responses (Malone T, et al. Current perspectives on targeting PIM kinases to overcome mechanisms of drug resistance and immune evasion in cancer. Pharmacol Ther. 2020 Mar;207).

[0010] Anaplastic lymphoma kinase (ALK) is a member of the insulin-like tyrosine kinase receptor family that is involved in the neoplasia of several tumor types. Approximately 5% of patients with non-small cell lung cancer (NSCLC) have anaplastic lymphoma kinase (ALK) gene rearrangement (Soda M et al., Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007, 448, 561-566). ALK inhibitors have been approved by the FDA as standard of care in the first-line and second-line treatment of patients with ALK rearranged NSCLC. However, since complete responses to ALK inhibitors are rare, almost all patients with ALK rearranged NSCLC inevitably acquire resistance to ALK inhibitors, which in turn causes tumor recurrence. Resistance mechanisms include ALK-independent and ALK-dependent processes. ALK-independent resistance mechanisms involve activation of bypass pathways, such as EGFR, c-MET, KRAS, and AXL, or transformation to small cell lung cancer (Gainor, JF et al., Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016, 6, 1118-1133). Although five ALK inhibitors have been approved, their clinical ability to overcome ALK-independent resistance mechanisms is limited. Therefore, there is a need to develop a new generation of multi-targeted ALK inhibitors that can not only target primary ALK fusions and ALK secondary resistance mutations, but also target mechanisms associated with resistant cancer cells to achieve better efficacy and longer response duration.

[0011] Proviral integration of Moloney murine leukemia virus (PIM) kinases is an oncogenic serine / threonine kinase that phosphorylates numerous substrates that regulate several cancer hallmarks, including tumor metabolism, survival, metastasis, immune evasion, and inflammation (Toth RK, Warfel NA, Targeting PIM Kinases to Overcome Therapeutic Resistance in Cancer. Mol Cancer Ther. 2021, 20(1):3-10). PIM kinases interact with many major oncogenic players, including stabilization of p53, synergistic effects with c-Myc, and significant parallel signaling with PI3K / Akt. Aberrant PIM kinase activity plays an important role in resistance mechanisms to chemotherapy, radiotherapy, anti-angiogenic therapy, and targeted therapies, providing a rationale for combination targeted therapy strategies for more durable patient responses (Malone T, et al. Current perspectives on targeting PIM kinases to overcome mechanisms of drug resistance and immune evasion in cancer. Pharmacol Ther. 2020 Mar;207).

[0012] Cdc-like kinases (CLKs) are evolutionarily conserved dual-specificity kinases capable of phosphorylating serine, threonine, and tyrosine residues. CLKs catalyze the phosphorylation of SR proteins, namely serine- and arginine-rich splicing factors 1-12 (SRSF1-12), which regulate the spliceosome molecular machinery (Martín Moyano P et al., Cdc-Like Kinases (CLKs): Biology, Chemical Probes, and Therapeutic Potential. Int J Mol Sci 2020, 21(20): 7549). Dysregulation of alternative splicing is a hallmark of cancer. High-frequency mutations of SF3B1 or SRSF2 in patients with myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, and acute myeloid leukemia (AML) have been described (Papaemmanuil et al., Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016, 374: 2209-2221). In addition, mutations in splicing-related genes have also been found in various solid cancers, including lung cancer, breast cancer, and pancreatic cancer (Dvinge H et al., RNA splicing factors as oncoproteins and tumour suppressors. Nat Rev Cancer 2016, 16: 413-430). Modulating pre-mRNA splicing via inhibition of CLK kinases is an attractive anti-tumor strategy, particularly for cancers that exhibit aberrant pre-mRNA splicing.

[0013] Therefore, there is a need to develop a new generation of multi-targeted EGFR inhibitors and multi-targeted ALK inhibitors that are effective against oncogenic driver EGFR mutations, ALK fusions and point mutations, other emerging and established EGFR and ALK resistance mutations, and emerging resistance targets (such as PIM kinases and CLK kinases) in resistant / persistent cancer cells. Summary of the Invention

[0014] In one aspect, the present disclosure provides a compound of formula I or a pharmaceutically acceptable salt thereof,

[0015]

[0016] where R 1 、R 2 、R 3 、R 4 , A, B, L, m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0017] In some embodiments, the present disclosure provides a compound of Formula II or a pharmaceutically acceptable salt thereof,

[0018]

[0019] where R 1 、R 2 、R 3 、R 4 , A, B, L, Y, m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0020] In some embodiments, the present disclosure provides a compound of formula III or a pharmaceutically acceptable salt thereof,

[0021]

[0022] where R 1 、R 2 、R 3 、R 4 ,A,B,L,Z,Z 1 、X 1 、X 2 、X 3 , m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0023] In some embodiments, the present disclosure provides a compound of formula IV or a pharmaceutically acceptable salt thereof,

[0024]

[0025] where R 1 、R 2 、R 3 、R 4 ,A,B,L,Z,Z 1 、X 1 、X 2 、X 3 , m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0026] In other aspects, the present disclosure relates to a pharmaceutical composition comprising at least one compound of formula (I)-(XII) or a pharmaceutically acceptable salt thereof.The pharmaceutical composition according to the present disclosure may further comprise a pharmaceutically acceptable excipient.

[0027] In other aspects, the present disclosure relates to a compound of Formula (I)-(XII) or a pharmaceutically acceptable salt thereof, which can be used as a medicament.

[0028] In other aspects, the present disclosure relates to a method of treating a disease, such as cancer, comprising administering to a subject in need of such treatment an effective amount of at least one compound of Formula (I)-(XII) or a pharmaceutically acceptable salt thereof.

[0029] In other aspects, the present disclosure relates to the use of compounds of Formula (I)-(XII) or pharmaceutically acceptable salts thereof in the preparation of a medicament for treating a disease, such as cancer, and the use of such compounds and salts for treating such diseases.

[0030] In other aspects, the present disclosure relates to a method of inhibiting EGFR (including certain mutations as described herein, PIM kinases and / or CLK kinases), comprising contacting a cell comprising one or more aberrant EGFR (including certain mutations as described herein, PIM kinases and / or CLK kinases) with an effective amount of at least one compound of Formula (I)-(XII) or a pharmaceutically acceptable salt thereof and / or with at least one pharmaceutical composition of the present disclosure, wherein the contacting is performed in vitro, ex vivo or in vivo.

[0031] Other embodiments, features and advantages of the present disclosure will be apparent from the following detailed description and through practice of the present disclosure. The disclosed compounds may be described as embodiments in any of the following enumerated clauses. It should be understood that any embodiment described herein may be used in combination with any other embodiment described herein to the extent that these embodiments do not contradict each other.

[0032] 1. A compound of formula I

[0033]

[0034] in

[0035] Ring A is a 5- to 10-membered heteroarylene group or a C6-C 10 arylene;

[0036] Ring B is a 5-membered heteroarylene group;

[0037] Each L is independently -O-, -S-, -S(O)-, -S(O)2-, -N(R 5 )C(O)-、-C(O)N(R 5 )-、-N(R 5 )-、-N(R 5 )S(O)-、-S(O)N(R 5 )-、-N(R 5 )S(O)2-、-S(O)2N(R 5 )-or-C(R 6 )(R 7 )-, provided that (L) p Does not contain OO, SO or NN bonds;

[0038] Each R 1 、R 2 and R 3 If present, independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C6 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a Rb 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, R c 、-OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NRc R d 、 -OS(O)2NR c R d 、 -SR c 、 -S(O)R c 、 -S(O)2R c 、 -S(O)NR c R d 、 -S(O)2NR c R d 、 -NR c R d 、 -NR c 、 -NR d 、 -N(C(O)R c )(C(O)R d )、 -NR c 、 -NR d 、 -NR c C(O)NR c R d 、 -NR c 、 -NR c R d 、 -NR c S(O)R d 、 -NR c S(O)2R d 、 -NR c S(O)NR c R d 、 -NR​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​2 or two R 3 and the atoms to which they are attached are optionally combined to form a C3-C6 cycloalkyl, a 3-membered to a 7-membered heterocycloalkyl, wherein when R 1 、R 2 and R 3 Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e Rf 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2;

[0040] R 4 H, deuterium, -C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-P(O)2R c R d 、-P(O)2NR c R d 、-P(O)2OR c or -S(O)2OR c ;

[0041] Each R 5 If present, independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, -C(O)R a , 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl or 5- to 10-membered heteroaryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in an aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with: -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2;

[0042] Each R 6 and R 7 are independently H, deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl and 5- to 10-membered heteroaryl groups is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2;

[0043] or R 5 、R 6 and R 7 The two of them, together with one or more atoms to which they are attached, are optionally combined to form a C3-C6 cycloalkyl group, a 3-membered to 7-membered heterocycloalkyl group, wherein when R 5 、R 6 and R 7Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2;

[0044] Each R a 、R b 、R c 、R d 、R e and R f independently selected from the group consisting of: H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10 aryl, 5- to 10-membered heteroaryl, and C1-C6 alkylene-5- to 10-membered heteroaryl, or R a and R b or R c and R d or R e and R f Together with the atoms to which they are attached, they form a 3- to 7-membered heterocycloalkyl group, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10Each hydrogen atom in an aryl, 5- to 10-membered heteroaryl, or C1-C6 alkylene-5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -OC1-C6 alkyl, -OC(O)-(H or C1-C6 alkyl), -OC(O)N(H or C1-C6 alkyl)2, -OC(O)N(C2-C6 alkylene), -OS(O)-(H or C1-C6 alkyl), -OS(O)2-(H or C1-C6 alkyl), -OS(O)N(H or C1-C6 alkyl)2, -OS(O)N(C2-C6 alkylene), -OS(O)2N(H or C1-C6 alkyl)2, -OS( C(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)O(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)N(H or C1-C6 alkyl) or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)C(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)2(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)2N(C2-C6 alkylene), -C(O)-(H or C1-C6 alkyl), -C(O)O (H or C1-C6 alkyl), -C(O)N(C2-C6 alkylene), -P(H or C1-C6 alkyl)2, -P(C2-C6 alkylene), -P(O)(H or C1-C6 alkyl)2, -P(O)(C2-C6 alkylene), -P(O)2(H or C1-C6 alkyl)2, -P(O)2(C2-C6 alkylene), -P(O)N(H or C1-C6 alkyl)2, -P(O)N(C2-C6 alkylene), -P(O)2N(H or C1-C6 alkyl)2, -P(O)2N(C2-C6 alkylene), -P(O)O(H or C1-C6 alkyl), -P(O)2O(H or C1-C6 alkyl), -CN or -NO2;

[0045] m is 0, 1, 2, 3 or 4;

[0046] n is 0, 1, 2, or 3;

[0047] p is 4, 5, 6, 7, 8, or 9; and

[0048] q is 0, 1, or 2;

[0049] or a pharmaceutically acceptable salt thereof;

[0050] Provided that the compound does not have the formula:

[0051]

[0052] or a pharmaceutically acceptable salt thereof.

[0053] 2. A compound of formula I

[0054]

[0055] in

[0056] Ring A is a 5- to 10-membered heteroarylene group or a C6-C 10 arylene;

[0057] Ring B is a 5-membered heteroarylene group;

[0058] Each L is independently -O-, -S-, -S(O)-, -S(O)2-, -N(R 5 )C(O)-、-C(O)N(R 5 )-、-N(R 5 )-、-N(R 5 )S(O)-、-S(O)N(R 5 )-、-N(R 5 )S(O)2-、-S(O)2N(R 5 )-or-C(R 6 )(R 7 )-, provided that (L) p Does not contain OO, SO or NN bonds;

[0059] Each R 1 、R 2 and R 3 If present, independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C6 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a Rb 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -ORc 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d )、-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR cR d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2;

[0060] R 4 H, deuterium, -C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-P(O)2R c R d 、-P(O)2NR c R d 、-P(O)2OR c or -S(O)2OR c ;

[0061] Each R 5 If present, independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl or 5- to 10-membered heteroaryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in an aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with: -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)Rc )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2;

[0062] Each R 6 and R 7 are independently H, deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NRa R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl and 5- to 10-membered heteroaryl groups is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NRe R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2;

[0063] or R 5 、R 6 and R 7 The two of them, together with one or more atoms to which they are attached, are optionally combined to form a C3-C6 cycloalkyl group, a 3-membered to 7-membered heterocycloalkyl group, wherein when R 5 、R 6 and R 7Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2;

[0064] Each R a 、R b 、R c 、R d 、R e and R f independently selected from the group consisting of: H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10 aryl, 5- to 10-membered heteroaryl, and C1-C6 alkylene-5- to 10-membered heteroaryl, or R a and R b or R c and R d or R e and R f Together with the atoms to which they are attached, they form a 3- to 7-membered heterocycloalkyl group, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10Each hydrogen atom in an aryl, 5- to 10-membered heteroaryl, or C1-C6 alkylene-5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -OC1-C6 alkyl, -OC(O)-(H or C1-C6 alkyl), -OC(O)N(H or C1-C6 alkyl)2, -OC(O)N(C2-C6 alkylene), -OS(O)-(H or C1-C6 alkyl), -OS(O)2-(H or C1-C6 alkyl), -OS(O)N(H or C1-C6 alkyl)2, -OS(O)N(C2-C6 alkylene), -OS(O)2N(H or C1-C6 alkyl)2, -OS( C(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)O(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)N(H or C1-C6 alkyl) or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)C(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)2(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)2N(C2-C6 alkylene), -C(O)-(H or C1-C6 alkyl), -C(O)O (H or C1-C6 alkyl), -C(O)N(C2-C6 alkylene), -P(H or C1-C6 alkyl)2, -P(C2-C6 alkylene), -P(O)(H or C1-C6 alkyl)2, -P(O)(C2-C6 alkylene), -P(O)2(H or C1-C6 alkyl)2, -P(O)2(C2-C6 alkylene), -P(O)N(H or C1-C6 alkyl)2, -P(O)N(C2-C6 alkylene), -P(O)2N(H or C1-C6 alkyl)2, -P(O)2N(C2-C6 alkylene), -P(O)O(H or C1-C6 alkyl), -P(O)2O(H or C1-C6 alkyl), -CN or -NO2;

[0065] m is 0, 1, 2, 3 or 4;

[0066] n is 0, 1, 2, or 3;

[0067] p is 4, 5, 6, 7, 8, or 9; and

[0068] q is 0, 1, or 2;

[0069] or a pharmaceutically acceptable salt thereof;

[0070] Provided that the compound does not have the formula:

[0071]

[0072] or a pharmaceutically acceptable salt thereof.

[0073] 3. The compound according to clause 1 or 2, or a pharmaceutically acceptable salt thereof, wherein (L) p Does not contain -NR directly covalently linked to ring A 5 C(O)-.

[0074] 4. A compound according to any one of the preceding clauses or a pharmaceutically acceptable salt thereof, wherein Ring A is C6-C 10 arylene, and m is 0, 1 or 2.

[0075] 5. The compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein ring A is phenylene, and m is 0, 1 or 2.

[0076] 6. The compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein ring A is phenylene, and m is 0 or 1.

[0077] 7. A compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein ring A is phenylene, m is 1, and R 1 Methyl, ethyl, F, Cl, Br, -CN, Each of these Indicates the point of covalent attachment.

[0078] 8. A compound according to any one of the preceding clauses or a pharmaceutically acceptable salt thereof, wherein Ring A is

[0079]

[0080] Each of these Indicates the point of covalent attachment.

[0081] 9. The compound according to any one of clauses 1 to 4, or a pharmaceutically acceptable salt thereof, wherein ring A is a 5- to 10-membered heteroarylene group, and m is 0, 1, 2 or 3.

[0082] 10. The compound according to any one of clauses 1 to 4, or a pharmaceutically acceptable salt thereof, wherein ring A is a 5- to 10-membered heteroarylene group, and m is 0, 1 or 2.

[0083] 11. The compound according to any one of clauses 1 to 4 or 10, or a pharmaceutically acceptable salt thereof, which has formula II:

[0084]

[0085] Wherein Y is a single bond, a double bond, -O-, -S-, =C(H)-, =C(R 1 )-、-N(H)-、-N(R 1 )- or =N-, and ring A is a 5- to 10-membered heteroarylene group.

[0086] 12. The compound of any one of clauses 1 to 4, 10 or 11, or a pharmaceutically acceptable salt thereof, which has formula III:

[0087]

[0088] Where Z is Where * is the same as (L) p The covalent attachment point is *not a NO or NN bond and **is a Z 1 The covalent attachment point, represents the point of covalent attachment to a ring atom of Ring A, and Indicates that at the connection point** and The situation where one bond is a single bond and one bond is a double bond; Z 1 for Among them, *** is The covalent connection point of Z 1 The covalent attachment point, represents the point of covalent attachment to a ring atom of Ring A, and Indicates the connection point **** with The condition where one bond between them is a single bond and one bond is a double bond, provided that Z and Z 1 are not nitrogen atoms; and Ring A is a 5- to 10-membered heteroarylene group.

[0089] 13. A compound according to any one of clauses 1 to 4, or 10 to 12, or a pharmaceutically acceptable salt thereof, which has formula IV:

[0090]

[0091] in

[0092] X 1 、X 2and X 3 are independently -O-, -S-, =C(H)-, =C(R 1 )-、-N(H)-、-N(R 1 )- or = N-, provided that X 1 、X 2 and X 3 At least one of them is not =C(H)- or =C(R 1 )-;

[0093] Z is Where * is the same as (L) p The covalent attachment point is *not a NO or NN bond and **is a Z 1 The covalent attachment point, represents the point of covalent attachment to a ring atom of Ring A, and Indicates that at the connection point** and The situation where one bond is a single bond and one bond is a double bond; Z 1 for Among them, *** is The covalent connection point of Z 1 The covalent attachment point, represents the point of covalent attachment to a ring atom of Ring A, and Indicates the connection point **** with The condition where one bond between them is a single bond and one bond is a double bond, provided that Z and Z 1 are not nitrogen atoms; and

[0094] Ring A is a 5- to 10-membered heteroarylene group.

[0095] 14. The compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroarylene group selected from the group consisting of:

[0096]

[0097]

[0098] Each of these Indicates the point of covalent attachment.

[0099] 15. The compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroarylene group selected from the group consisting of:

[0100]

[0101] Each of these Indicates the point of covalent attachment.

[0102] 16. The compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroarylene group selected from the group consisting of:

[0103]

[0104]

[0105]

[0106]

[0107] Each of these Indicates the point of covalent attachment.

[0108] 17. The compound of any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0109]

[0110] Each of these Indicates the point of covalent attachment.

[0111] 18. The compound of any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0112]

[0113] Each of these Indicates the point of covalent attachment.

[0114] 19. The compound of any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0115]

[0116] Each of these Indicates the point of covalent attachment.

[0117] 20. The compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein q is 0, 1 or 2.

[0118] 21. The compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein q is 0 or 1.

[0119] 22. A compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein R 3 For F.

[0120] 23. A compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein R 4 is H or methyl.

[0121] 24. A compound according to any of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein each L is independently -C(R 6 )(R 7 )-, -C(O)-, -O- or -N(R 5 )-, provided that (L) p Does not contain -OO- or -ON(R 5 )-key, and (L) p The point of covalent attachment to Ring A does not form an -NN- or -ON- bond.

[0122] 25. A compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein -(L) p -for-CR 6 R 7 -O(CR 6 R 7 )2O-、-CR 6 R 7 -O(CR 6 R 7 )3O-、-(CR 6 R 7 )C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )N(R 5 )C(O)-(CR 6 R 7 )2-、-O(CR 6 R 7 )2N(R 5 )C(O)-(CR 6 R 7 )O-、-N(R 5 )-C(O)(CR 6 R 7 )2O(CR 6 R 7 )2-、-CR 6 R 7 O(CR 6 R 7 )2O-(CR 6 R 7 )2、-O(CR 6 R 7 )2O(CR 6 R 7)2O-、-CR 6 R 7 O-CR 6 R 7 -C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )3O(CR 6 R 7 )2-、-(CR 6 R 7 )2O(CR 6 R 7 )3-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )4O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3-、-O(CR 6 R 7 )2O-CR 6 R 7 -、-O(CR 6 R 7 )2O(CR 6 R 7 )2-、-O(CR 6 R 7 )2O(CR 6 R 7 )3-、-(CR 6 R 7)2-N(R 5 )-(CR 6 R 7 )3-、-O(CR 6 R 7 )2-N(R 5 )-CR 6 R 7 -、-(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )2-、-O-(CR 6 R 7 )2-、-O-(CR 6 R 7 )3-、-O-(CR 6 R 7 )4-、-O-(CR 6 R 7 )5-、-O-(CR 6 R 7 )2O-、-O-(CR 6 R 7 )3O-、-O-(CR 6 R 7 )4O-or-O-(CR 6 R 7 )5O-.

[0123] 26. A compound according to any of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein each R 5 are independently H, methyl, ethyl, -C(O)CH3 or -C(O)CH2CH3; or R 5 If it exists, and R 6 or R 7 If present, together with the one or more atoms to which it is attached, they form a 3- to 7-membered heterocycloalkyl group; wherein when R 5 and R 6 or R 7 Each hydrogen atom in the 3- to 7-membered heterocycloalkyl group formed when joined together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SRe 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0124] 27. A compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein R 6 and R 7 If present, together with the one or more atoms to which it is attached, they form a 3- to 7-membered heterocycloalkyl group; wherein when R 6 and R 7 Each hydrogen atom in the 3- to 7-membered heterocycloalkyl group formed when joined together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e Rf 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0125] 28. A compound according to any one of the preceding clauses or a pharmaceutically acceptable salt thereof, wherein R 5 or R 7 Each R combined 6are independently H or C1-C6 alkyl.

[0126] 29. A compound according to any one of the preceding clauses or a pharmaceutically acceptable salt thereof, wherein R 5 or R 7 Combined with an R 6 is methyl, and the remaining R 6 and R 7 For H.

[0127] 30. A compound according to any one of the preceding clauses, or a pharmaceutically acceptable salt thereof, wherein -(L) p- is -O-(CH2)2O-CH2-, -OC(H)(CH3)-CH2-O-CH2-, -CH2O-(CH2)2O-, -C(H)(CH3)-O-(CH2)2O-, -CH2N(H)-(CH2)2O-, -CH2N(CH3)-(CH2)2O-, -CH2N(CH2CH3)-(CH2)2O-, -O(CH2)2N(H)CH2-, -O(CH2)2N(CH3)CH2-, -OCH2-C(H)(CH3)-N(CH(CH3)2)CH2-, -OCH2-C(H)(CH2F)-N(CH3)CH2-, -OCH2-C(H)(CH2CH3)-N(CH3)CH2-, -O(CH2)2N(C(O)CH3)CH2-, -OC(H)(CH3)CH2N(H)CH2-, -OC(H)(CH3)CH2N(CH3)CH2-, -OC(H)(CH2CN)CH2N(CH3)CH2-, -OC(H)(CH2CH3)CH2N(CH3)CH2-, -OC(H)(CH2F)CH2N(CH3)CH2-, -OC(H)(CHF2)CH2N(CH3)CH2-, -OC(H)(CH2OH)CH2N(CH3)CH2-, -OC(H)(CH3)C(O)N(CH3)CH2-, -OC(H)(cyclobutyl)CH2N(CH3)CH2-, -OC(H)(CH3)CH2N(CH2CH3)CH2-, -OC(H)(CH3)CH2N(CH(CH3)2)-CH2-, -OC(H)(CH3)CH2N(CH3)-C(H)(CH3)-, -OC(H)(CH3)CH2N(oxetan-3-yl)-CH2-, -OC(H)(CH3)CH2N(cyclopropyl)-CH2-, -OCH2C(H)(CH3)N(cyclopropyl)-CH2-, -OC(H)(CH3)CH2N(C(O)CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH2CH3)CH2-, -CH2N(H)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-C(H)(CH3)-CH2O-, -CH2N(CH3)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-(CH2)-(C(H)CH3)O-, -O(CH2)2-, -O(CH2)3-, -O(CH2)4-, -O(CH2)3O-, -O(CH2)4O-, -O(CH2)5O-, -O-(C(H)(CH3)-(CH2)2O-, -O(CH2)2-C(H)(CH3)-O--O(CH2)2C(H)(CH3)CH2O-, -O(CH2)3C(H)(CH3)CH2O-, -O(CH2)2N(H)C(O)-(CH2)O-, -O(CH2)2N(CH3)C(O)-(C H2)O-, -O(CH2)2O(CH2)2O-, -OC(H)(CH3)CH2OCH2-, -O(CH2)2OCH2C(H)(CH3)O-, -O(CH2)2OC(H)(CH3)-CH2O-,

[0128] 31. The compound of clause 1 or 2, which is selected from the group consisting of: (11E)-1-methyl-1,18,19,21-tetrahydro-8H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-f][1,4,12,13]benzodioxadiazacyclooctadecine;

[0129] (11E)-1-[(methylsulfonyl)methyl]-19,20-dihydro-1H,8H,18H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-f][1,5,12,13]benzodioxadiazacyclooctadecane;

[0130] (11E)-1-methyl-18,19,20,21-tetrahydro-1H,8H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-g][1,6,13,14]benzodioxadiazacyclononadecanone (nonadecine);

[0131] (10R,16E)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0132] (10R,16E)-3-methyl-13-[(4-methylpiperazin-1-yl)methyl]-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0133] (10R,16E)-13-[(dimethylamino)methyl]-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0134] (10R,16E)-3-methyl-13-(1-methylpiperidin-4-yl)-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0135] (10R,16E)-13-(2-methoxypropan-2-yl)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0136] (10R,16E)-3-methyl-13-(4-methylpiperazin-1-yl)-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0137] (10R,16E)-14-fluoro-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0138] (10R,16E)-14-(2-hydroxypropan-2-yl)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0139] (10R,16E)-14-{(2S)-2-[(methylsulfonyl)methyl]azetidin-1-yl}-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepin-25-one;

[0140] (10R,16E)-3-methyl-25-oxo-3,5,6,9,10,19-hexahydro-8H-20,22-etheno-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-14-carbonitrile; and

[0141] (10R,16E)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecane;

[0142] or a pharmaceutically acceptable salt thereof.

[0143] 32. The compound of clause 1 or 2, which is selected from the group consisting of: (18E)-8-methyl-N-(propan-2-yl)-8,9,11,12-tetrahydro-2H-3,5-ethene-bridged bispyrazolo[3′,4′:9,10;4″,3″:13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0144] (18E)-N,8-dimethyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0145] (18E)-N,N,8-trimethyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0146] (18E)-N-ethyl-8-methyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0147] (10S,18E)-8,10,16-trimethyl-2,8,11,12-tetrahydro-10H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,5]dioxacyclopentadecafluoro[7,6-b]pyridine;

[0148] (10S,18E)-17-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-ethylene-bridged bipyrazolo[3,4-j:4',3'-n]pyrido[4,3-f][1,4]oxazacyclopentadecine; and

[0149] (10S,18E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-ethylene-bridged bipyrazolo[3,4-j:4',3'-n]pyrido[3,2-f][1,4]oxazaheterocyclopentadecane;

[0150] or a pharmaceutically acceptable salt thereof.

[0151] 33. The compound of clause 1 or 2, which is selected from the group consisting of: (17E)-8,14,16-trimethyl-2,8,9,11,12,14-hexahydro-3,5-etheno[1,4]dioxopentadecano[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0152] 2-[(17E)-8,9,16-trimethyl-8,9,11,12-tetrahydro-3,5-vinyl-bridged [1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazol-14(2H)-yl]ethan-1-ol;

[0153] (17E)-8,14,16-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0154] (17E)-19-Fluoro-8,14,16-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0155] (17E)-16-Ethyl-8,14-dimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0156] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-2-methylpropan-2-ol;

[0157] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]propan-2-one;

[0158] 2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethan-1-ol;

[0159] (17E)-8,16-Dimethyl-14-[2-(pyrrolidin-1-yl)ethyl]-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0160] (3S)-1-{2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethyl}pyrrolidin-3-ol;

[0161] (17E)-16-Ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0162] (10S,17E)-8,10,14,16-tetramethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0163] (10R,17E)-8,10,14,16-tetramethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0164] (12S,17E)-16-Ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0165] (12R,17E)-16-ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0166] (10S,17E)-16-Ethyl-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0167] (10S,17E)-16-cyclopropyl-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0168] (17E)-16-(methoxymethyl)-8,14-dimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0169] (17E)-8,14,16-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0170] 1-[(17E)-8,14,16-trimethyl-2,8,10,11,13,14-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0171] (17E)-8,12,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0172] (17E)-6,8,12,14,16-pentamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethylenetriazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0173] (17E)-16-Ethyl-8,12,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0174] (17E)-7,14,16-trimethyl-2,10,11,12,13,14-hexahydro-7H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0175] (17E)-7,12,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-7H-3,5-ethylenetriazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0176] 2-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0177] (17E)-8,14,16-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0178] (17E)-8,10,14,16-tetramethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0179] 2-[(17E)-8,16-dimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0180] 2-[(17E)-8,10,16-trimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0181] 2-[(17E)-10-ethyl-8,16-dimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0182] (19E)-8,13,16,18-Tetramethyl-2,11,12,13,14,16-hexahydro-8H,10H-3,5-ethenyl[1,7]dioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0183] 2-[(19E)-8,13,18-Trimethyl-2,8,11,12,13,14-hexahydro-10H,16H-3,5-vinyl-bridged [1,7]dioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazol-16-yl]ethan-1-ol;

[0184] (19E)-8,16,18-trimethyl-2,11,12,16-tetrahydro-8H,10H-3,5-ethene-bridged tripyrazolo[3,4-h:3',4'-l:4",3"-p][1,7,4]dioxazacycloheptadecan-13(14H)-one;

[0185] (19E)-8,12,16,18-tetramethyl-2,11,12,16-tetrahydro-8H,10H-3,5-ethylenetriazolo[3,4-h:3',4'-l:4",3"-p][1,7,4]dioxazacycloheptadecan-13(14H)-one;

[0186] (13R,19E)-8,13,16,18-tetramethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0187] (13S,19E)-8,13,16,18-tetramethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxetane heptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0188] 2-[(19E)-8,13,18-trimethyl-2,8,10,11,13,14-hexahydro-16H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazol-16-yl]ethan-1-ol;

[0189] (19E)-8,13,18-Trimethyl-16-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0190] (3S)-1-{2-[(17E)-16-ethyl-8-methyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethyl}pyrrolidin-3-ol;

[0191] (19E)-22-Fluoro-8,16,18-trimethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0192] 3-[(17E)-16-Ethyl-8-methyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-N,N-dimethylpropan-1-amine;

[0193] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]pyrrolidin-3-ol;

[0194] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-1-methylpyrrolidin-3-ol;

[0195] (3R,4S)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]oxolan-3-ol;

[0196] (3S,4R)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]oxolan-3-ol;

[0197] (rac)-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutan-1-ol;

[0198] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]piperidin-3-ol;

[0199] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-1-methylpiperidin-3-ol;

[0200] (rac)-1,5-anhydro-2,3-dideoxy-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-L-threo-pentitol;

[0201] (rac)-1,5-anhydro-2,4-dideoxy-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-L-threopentitol;

[0202] (12R,17E)-8,10,12,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0203] (12S,17E)-8,10,12,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0204] (rac)-(3S,4S)-1-methyl-4-[(17E)-8,10,16-trimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]pyrrolidin-3-ol;

[0205] (11S,17E)-8,11,14,16-tetramethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0206] (17E)-8,9,16-Trimethyl-14-[2-(pyrrolidin-1-yl)ethyl]-2,8,9,11,12,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0207] [(10S,17E)-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-16-yl]methanol;

[0208] N 1 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutyl}-N 1 ,N 2 ,N 2 -Trimethylethylene-1,2-diamine;

[0209] (11S,17E)-8,10,11,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0210] N 2 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutyl}-N 1 ,N 1 -dimethylethylene-1,2-diamine;

[0211] (10R,15E)-3,12,14-trimethyl-5,6,9,10,12,18-hexahydro-3H,8H-19,21-ethenyl-7,10-methantripyrazolo[3,4-i:3',4'-m:4",3"-q][1,8,4]dioxazacyclooctadecan-24-one;

[0212] (17E)-16-Ethyl-8,10,14-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0213] (17E)-10-ethyl-8,14,16-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0214] 2-[(10S,17E)-8,10,16-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0215] 2-[(10S,17E)-19-fluoro-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0216] (17E)-8,10,16-trimethyl-14-(1-methylpyrrolidin-3-yl)-2,9,10,11,12,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0217] 2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0218] (10S,17E)-8,10,12,14,16-pentamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0219] (10R,19E)-8,16,18-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0220] (2S)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-2-ol;

[0221] 2-[(10S,17E)-19-chloro-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0222] (2R)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-2-ol;

[0223] 2-[(10S,17E)-16-ethyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0224] 2-[(10S,17E)-12-ethyl-8,10,16-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0225] (10S,17E)-8,10,12,14-tetramethyl-16-[(piperidin-4-yl)oxy]-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0226] 2-[(10R,19E)-18-Ethoxy-8-methyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0227] 2-[(10S,17E)-6,8,10,12,16-pentamethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0228] (10S,17E)-8,10,14,16-tetramethyl-12-(oxetan-3-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0229] 2-[(10S,17E)-16-ethoxy-6,8,10-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0230] (10S,17E)-16-{[1-(methylsulfonyl)piperidin-4-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0231] (10S,13R,17E)-8,10,12,13,14,16-hexamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0232] (10S,13S,17E)-8,10,12,13,14,16-hexamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0233] 2-{(10S,17E)-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0234] (10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0235] (10S,17E)-16-[(azetidin-3-yl)oxy]-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0236] (10S,17E)-16-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0237] 2-[(10S,17E)-16-ethoxy-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0238] 2-[(17E)-10-cyclobutyl-8,12,16-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0239] (10S,17E)-8,10,12,14-tetramethyl-16-{[(3S)-pyrrolidin-3-yl]oxy}-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0240] (10S,17E)-16-{[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0241] (2S)-2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0242] (10S,17E)-16-ethoxy-8,10,14-trimethyl-12-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0243] (10S,17E)-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[0244] (10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-16-carbonitrile;

[0245] (10R,19E)-18-Ethoxy-8,16-dimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0246] (10S,17E)-12-cyclopropyl-8,10,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0247] (10S,17E)-8,10,12,14-tetramethyl-16-(2,2,2-trifluoroethoxy)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0248] {[(10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile;

[0249] (10S,17E)-10,14,16-trimethyl-8-[(methylthio)methyl]-12-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0250] (10S,17E)-12-Ethyl-8,10,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0251] 2-[(10S,17E)-16-ethoxy-8-ethyl-10,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0252] 2-{(10S,17E)-8-ethyl-10,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0253] (2R)-2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0254] 2-[(10S,17E)-16-ethoxy-19-fluoro-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0255] 2-[(10S,17E)-16-{[1-(methylsulfonyl)piperidin-4-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0256] (10S,19E)-8,16,18-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0257] 2-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0258] 2-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0259] 2-{(10S,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0260] 2-[(10S,17E)-16-{[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0261] 2-[(10S,17E)-16-bromo-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0262] 2-{(10S,17E)-16-[(azetidin-3-yl)oxy]-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0263] (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0264] (10S,17E)-16-{[3-(methylsulfonyl)cyclobutyl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0265] (10S,19E)-18-Ethoxy-8,16-dimethyl-2,8,11,12,15,16-hexahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane-13(10H)-one;

[0266] (10R,19E)-18-Ethoxy-8,16-dimethyl-2,8,11,12,15,16-hexahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane-13(10H)-one;

[0267] 2-[(10R,19E)-18-Ethoxy-22-fluoro-8-methyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0268] 2-{(11S,17E)-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0269] 2-{(10R,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0270] 2-{(11S,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0271] 2-{(10R,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0272] 2-[(10R,17E)-12-cyclopropyl-16-ethoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0273] 2-[(10R,17E)-16-ethoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0274] 2-[(11S,17E)-12-cyclopropyl-16-ethoxy-8,11-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0275] 2-[(10R,19E)-22-fluoro-8-methyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0276] (2S)-2-{(10S,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0277] 2-{(11S,17E)-6,8,11-trimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0278] 2-{(10R,17E)-6,8,10-trimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0279] {[(10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile;

[0280] 2-[(10R,17E)-12-cyclopropyl-16-ethoxy-6,8,10-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0281] 2-[(11S,17E)-12-cyclopropyl-16-ethoxy-6,8,11-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0282] (10S,17E)-16-Ethoxy-12-ethyl-19-fluoro-8,10,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0283] (2S)-2-{(10R,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0284] (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-16-carbonitrile;

[0285] (10S,17E)-12-Ethyl-8,10,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0286] (10S,17E)-19-Fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0287] 2-[(10S,17E)-19-fluoro-8,10,12-trimethyl-16-(2,2,2-trifluoroethoxy)-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0288] 2-{(10R,17E)-12-cyclopropyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0289] 2-{(11S,17E)-12-cyclopropyl-8,11-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0290] (2S)-2-[(10S,17E)-16-ethoxy-19-fluoro-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0291] (2S)-2-[(10S,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0292] 2-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0293] 1-[(10R,17E)-16-ethoxy-14-(2-hydroxyethyl)-8,10-dimethyl-2,8,10,11,13,14-hexahydro-12H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0294] Ethyl [(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]acetate;

[0295] (2S)-2-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0296] (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,12,13,14-tetrahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-11(10H)-one;

[0297] 2-[(10S,17E)-16-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0298] 1-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]-2-methylpropan-2-ol;

[0299] 2-{(10S,13R,17E)-8,10,12,13-tetramethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0300] 2-{(10S,13S,17E)-8,10,12,13-tetramethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0301] 2-{(17E)-10-(Fluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0302] 2-{(17E)-11-(Fluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0303] (2S)-1-{(10R,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol;

[0304] (2S)-2-[(11S,17E)-16-Ethoxy-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0305] (2S)-2-[(10R,17E)-16-ethoxy-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0306] (2S)-2-{(11S,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0307] (2S)-2-{(10R,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0308] 2-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}acetamide;

[0309] (10S,17E)-19-Fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0310] 2-[(8aR,19E)-1-(cyclopropylmethoxy)-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0311] (10R,18E)-17-ethoxy-8,15-dimethyl-2,8,11,12,14,15-hexahydro-10H-3,5-ethenyl-10,13-methanotripyrazolo[3,4-g:3',4'-k:4",3"-o][1,5]oxazahexadecine;

[0312] {(17E)-14-(2-hydroxyethyl)-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,10,11,12,13,14-hexahydro-7H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-7-yl}acetonitrile;

[0313] (17E)-16-Ethoxy-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno-10,12-methanotripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0314] 2-[(10S,17E)-16-Ethoxy-19-fluoro-6,8,10-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0315] 2-[(8aR,9R,19E)-1-ethoxy-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0316] 2-[(8aR,9S,19E)-1-ethoxy-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0317] 2-[(19E)-18-Ethoxy-8,21-dimethyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0318] 2-[(8aR,9R,19E)-1-ethoxy-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0319] 2-[(8aR,9S,19E)-1-ethoxy-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0320] 2-[(19E)-18-Ethoxy-22-fluoro-8,21-dimethyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0321] 2-{(10S,17E)-8-cyclopropyl-10,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0322] (10S,13S,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0323] (10R,13R,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0324] (10R,13S,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0325] (10S,13R,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0326] 2-{(10R,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0327] 2-[(8aR,9S,19E)-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0328] 2-[(8aR,9R,19E)-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0329] 2-[(19E)-8,21-Dimethyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0330] 2-[(8aR,9R,19E)-22-fluoro-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0331] 2-[(8aR,9S,19E)-22-fluoro-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0332] 2-[(19E)-22-Fluoro-8,21-dimethyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0333] 2-{(10R,17E)-10-(hydroxymethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0334] 2-[(11S,17E)-16-ethoxy-11-ethyl-8,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0335] 2-[(10S,17E)-16-ethoxy-10-ethyl-8,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0336] 2-[(10S,17E)-16-(methoxymethyl)-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0337] 1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}-2-methylpropan-2-ol;

[0338] 1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-one;

[0339] (10R,17E)-14-(2-hydroxyethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-10-carbonitrile;

[0340] 2-{(10S,17E)-8,10,12-trimethyl-16-[(methylamino)methyl]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0341] 2-{(10S,17E)-16-[(dimethylamino)methyl]-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0342] (2R)-2-{[(10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}propionitrile;

[0343] (2S)-2-{[(10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}propionitrile;

[0344] 2-[(4aS,7aS,13E)-12-ethoxy-3,6,8-trimethyl-4a,5,6,7,7a,8,9,16-octahydro-17,19-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecan-10(3H)-yl]ethan-1-ol;

[0345] 2-[(4aR,7aR,13E)-12-ethoxy-3,6,8-trimethyl-4a,5,6,7,7a,8,9,16-octahydro-17,19-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecan-10(3H)-yl]ethan-1-ol;

[0346] {[(8aR,19E)-3-(2-hydroxyethyl)-9,11-dimethyl-3,4,7,8,8a,9,11,17-octahydro-6H-14,16-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-1-yl]oxy}acetonitrile;

[0347] {[(8aR,9R,19E)-3-(2-hydroxyethyl)-9,11-dimethyl-3,4,7,8,8a,9,11,17-octahydro-6H-14,16-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-1-yl]oxy}acetonitrile;

[0348] 2-{(10S,17E)-10-(difluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0349] 2-{(10R,17E)-10-(difluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0350] 2-{(10S,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0351] 2-[(10R,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0352] (4aS,7aS,13E)-12-ethoxy-3,8,10-trimethyl-3,4a,5,6,7,7a,8,9,10,16-decahydro-17,19-ethylene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecane;

[0353] (4aR,7aR,13E)-12-ethoxy-3,8,10-trimethyl-3,4a,5,6,7,7a,8,9,10,16-decahydro-17,19-ethylene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecane;

[0354] (2S)-1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol;

[0355] 2-{(11R,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0356] 2-{(10S,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0357] 2-[(11R,17E)-16-ethoxy-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0358] 2-[(10S,17E)-16-ethoxy-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0359] {[(10S,17E)-19-Fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile;

[0360] 2-[(10R,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0361] (2S)-2-[(10R,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0362] 2-[(10S,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0363] (2S)-2-[(10R,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0364] (10S,17E)-16-Ethoxy-12-ethyl-14-(2-hydroxyethyl)-8,10-dimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-6-carbonitrile;

[0365] 2-[(10S,17E)-16-ethoxy-6-ethynyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0366] 2-[(10S,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0367] 2-[(10S,17E)-16-(ethylamino)-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0368] (2S)-1-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol;

[0369] 2-[(10S,17E)-6-amino-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0370] (2S)-2-[(10S,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0371] 2,2'-[(10S,17E)-10,12-dimethyl-16-[(propan-2-yl)oxy]-10,11,12,13-tetrahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-8,14(2H)-diyl]di(ethan-1-ol);

[0372] (17E)-16-Ethyl-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0373] 2-[(17E)-8,16-dimethyl-2,10,11,13-tetrahydro-3,5-vinyl-bridged [1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14(8H)-yl]-N-ethylacetamide;

[0374] (17E)-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[0375] (17E)-8,14,16-trimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0376] (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0377] (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[0378] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[6,5-d][1,2]oxazole-16-carbonitrile;

[0379] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[6,5-d][1,2]thiazole-16-carbonitrile;

[0380] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecafluoro[5,6-c][1,2]oxazole-16-carbonitrile;

[0381] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecafluoro[5,6-c][1,2]thiazole-16-carbonitrile; and

[0382] (10S,17E)-16-Ethyl-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0383] or a pharmaceutically acceptable salt thereof.

[0384] 34. The compound of clause 1 or 2, which is selected from the group consisting of: (17E)-8,15,16-trimethyl-2,8,9,11,12,15-hexahydro-3,5-etheno[1,4]dioxopentadecano[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0385] (17E)-8,15,16-trimethyl-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0386] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]propan-2-one;

[0387] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl-bridged[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-2-methylpropan-2-ol;

[0388] 2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]ethan-1-ol;

[0389] (17E)-8,16-Dimethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0390] (10S,17E)-8,10,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0391] (17E)-8,15,16-trimethyl-2,10,11,12,13,15-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0392] 1-[(17E)-8,15,16-trimethyl-2,8,10,11,13,15-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0393] (17E)-8,12,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0394] 1-[(10S,17E)-8,10,15,16-tetramethyl-2,8,10,11,13,15-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0395] (10S,17E)-8,10,12,15,16-pentamethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0396] 2-[(10S,17E)-8,10,16-trimethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]ethan-1-ol;

[0397] 2-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]ethan-1-ol;

[0398] (10S,17E)-12-Ethyl-8,10,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0399] 1-[(10S,17E)-8,10,15,16-tetramethyl-2,8,10,11,13,15-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]propan-1-one;

[0400] 2-[(19E)-8,13,18-Trimethyl-2,8,11,12,13,14-hexahydro-10H,17H-3,5-vinyl[1,7]dioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazol-17-yl]ethan-1-ol;

[0401] (13E)-3-methyl-3,5,6,7,8,16-hexahydro-9,12-(azeno)-17,19-ethylene-bridged bipyrazolo[3,4-1:4',3'-p][1,6]oxazaheterocycloheptadecane;

[0402] (18E)-8-Methyl-2,8,10,11,12,13-hexahydro-3,5-ethylenetripyrazolo[1,5-f:3',4'-j:4",3"-n][1,6]oxazacyclopentadecane;

[0403] (17E)-15-(2-methoxyethyl)-8,16-dimethyl-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0404] 2-[(17E)-8,9,16-trimethyl-8,9,11,12-tetrahydro-3,5-vinyl-bridged [1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazol-15(2H)-yl]ethan-1-ol;

[0405] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]piperidin-3-ol;

[0406] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-1-methylpiperidin-3-ol;

[0407] (17E)-8,9,16-Trimethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,8,9,11,12,15-hexahydro-3,5-etheno[1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0408] (rac)-1,5-anhydro-2,3-dideoxy-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-L-threopentitol;

[0409] 1,5-Anhydro-2,4-dideoxy-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-L-threopentitol;

[0410] (10S,17E)-8,10,12,16-tetramethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0411] (10S,17E)-8,10,12,16-tetramethyl-15-[2-(4-methylpiperazin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0412] (20E)-8,18-dimethyl-2,8,11,12-tetrahydro-10H-3,5-ethylene-bridged bispyrazolo[3",4":10',11';4"',3"':14',15'][1,5]dioxacyclopentadecano[6',7':3,4]pyrazolo[1,5-a]pyrazin-19(18H)-one;

[0413] (10S,17E)-8,10,12,16-tetramethyl-15-[2-(morpholin-4-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0414] 4-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]butan-2-ol;

[0415] N 1 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]cyclobutyl}-N 1 ,N 2 ,N 2 -Trimethylethylene-1,2-diamine;

[0416] 2-Methyl-4-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]butan-2-ol;

[0417] 2-Methyl-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol;

[0418] N2-{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]cyclobutyl}-N 1 ,N 1 -dimethylethylene-1,2-diamine;

[0419] (17E)-8,10,16-trimethyl-15-(1-methylpyrrolidin-3-yl)-2,9,10,11,12,15-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0420] (10R,17E)-8,10,12,16-tetramethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0421] (2S)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol;

[0422] (10S,17E)-8,10,12,14,15-pentamethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0423] (2R)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol;

[0424] (10S,17E)-8,10,12,14,16-pentamethyl-2,10,11,12,13,16-hexahydro-8H-3,5-ethylenetripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0425] (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[3,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0426] (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0427] (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-ethylene-bridged bipyrazolo[3,4-j:4',3'-n][1,2]thiazolo[3,4-f][1,4]oxazacyclopentadecane;

[0428] (10S,20E)-18-[2-(methylsulfonyl)ethyl]-8,10,12-trimethyl-2,8,10,11,12,13,16,17,18,19-decahydro-3,5-vinyl-bridged pyrazino[1',2':1,5]pyrazolo[3,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0429] (10S,17E)-16-cyclopropyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0430] (10S,17E)-16-Ethyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0431] (10S,17E)-8,10,12-trimethyl-16-(propan-2-yl)-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0432] (10S,17E)-8,10,12-trimethyl-16-(propan-2-yl)-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0433] (10S,17E)-16-Ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2] oxazolo [5,4-f] bipyrazolo [3,4-j: 4',3'-n][1,4] oxazacyclopentadecane;

[0434] (10R,17E)-8,10,14,15-tetramethyl-12-(propan-2-yl)-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0435] (10S,17E)-8,10,14,15-tetramethyl-12-(propan-2-yl)-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0436] (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]oxazole;

[0437] (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]oxazole-16-carbonitrile;

[0438] (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole;

[0439] (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole-16-carbonitrile;

[0440] (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole;

[0441] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile;

[0442] (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]thiazole;

[0443] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile;

[0444] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]thiazole-16-carbonitrile;

[0445] (17E)-8,16-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole;

[0446] (17E)-8,16-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylenedipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecafluoro[7,6-d][1,2]oxazole; and

[0447] (17E)-8,16-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecafluoro[6,7-c][1,2]thiazole;

[0448] or a pharmaceutically acceptable salt thereof.

[0449] 35. A pharmaceutical composition comprising a compound as defined in any one of the preceding clauses and optionally one or more excipients.

[0450] 36. A method of treating a disease in a subject comprising administering a therapeutically effective amount of a compound according to any one of clauses 1 to 34 or a pharmaceutical composition according to clause 35.

[0451] 37. A compound according to any one of clauses 1 to 34 for use in a method of treating a disease in a subject.

[0452] 38. Use of a compound according to any one of clauses 1 to 34 in the manufacture of a medicament for treating a disease in a subject. DETAILED DESCRIPTION

[0453] Before further describing the present disclosure, it should be understood that the present disclosure is not limited to the particular embodiments described, as such may, of course, vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting, as the scope of the present disclosure will be limited only by the appended claims.

[0454] For the sake of brevity, the disclosures of the publications (including patents) listed in this specification are incorporated herein by reference. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs. All patents, applications, published applications and other publications mentioned herein are incorporated herein by reference in their entirety. If the definition set forth in this section is contrary to or otherwise inconsistent with the definition set forth in the patents, applications or other publications incorporated herein by reference, then relative to the definition incorporated herein by reference, the definition set forth in this section shall prevail.

[0455] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It should be further noted that the claims may be drafted to exclude any optional elements. Thus, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only," and the like in connection with the recitation of claim elements, or for use of a "negative" limitation.

[0456] As used herein, the terms "including," "containing," and "comprising" are used in their open, non-limiting sense.

[0457] To provide a more concise description, some of the quantitative expressions given herein are not limited by the term "about". It should be understood that, regardless of whether the term "about" is explicitly used, each quantity given herein is intended to refer to the actual given value, and it is also intended to refer to the approximate value of the given value reasonably inferred by a person of ordinary skill in the art, including equivalent values ​​and approximate values ​​obtained due to the experimental and / or measurement conditions of the given value. Whenever the yield is given as a percentage, the yield refers to the mass of the same entity relative to the maximum amount of the entity that can be obtained under specific stoichiometric conditions, wherein the yield is given for the entity. Unless otherwise indicated, the concentration given as a percentage refers to the mass ratio.

[0458] Unless otherwise specified, 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. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of this disclosure, preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials related to the cited publications.

[0459] Unless otherwise indicated, the methods and techniques of the disclosed embodiments are generally performed according to conventional methods well known in the art and as described in various general and more specific references cited and discussed throughout this specification. See, for example, Loudon, Organic Chemistry, 4th ed., New York: Oxford University Press, 2002, pp. 360-361, 1084-1085; Smith and March, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th ed., Wiley-Interscience, 2001.

[0460] Chemical nomenclature of compounds described herein was generally generated using the commercially available ACD / Name 2014 (ACD / Labs) or ChemBioDraw Ultra 13.0 (Perkin Elmer).

[0461] As used herein and in connection with depicting the chemical structures of various embodiments described herein, "*," "**," and Indicates the point of covalent attachment of the chemical group or chemical structure in which the identifier is displayed to an adjacent chemical group or chemical structure. For example, in a hypothetical chemical structure AB, where A and B are joined by a covalent bond, in some embodiments, the portion of AB bounded by the group or chemical structure A may be represented by "A-*", "A-**" or Indicates that "-*", "-**" and Each of represents a bond to A and a point of covalent attachment to B. Alternatively, in some embodiments, the portion of AB defined by a group or chemical structure B may be represented by "*-B," "**-B," or Indicates that "-*", "-**" and Each of represents a bond to B and a point of covalent attachment to A.

[0462] It should be understood that certain features of the disclosure described in the context of a separate embodiment for clarity may also be provided in combination in a single embodiment. Conversely, the various features of the disclosure described in the context of a single embodiment for brevity may also be provided separately or in any suitable sub-combination. All combinations of embodiments related to the chemical groups represented by the variables are specifically encompassed by the disclosure and disclosed herein, just as each combination is individually and clearly disclosed, as long as the compounds encompassed by these combinations are stable compounds (compounds that can be separated, characterized, and tested for biological activity). In addition, all sub-combinations of the chemical groups listed in the embodiments describing such variables are also particularly encompassed by the disclosure and disclosed herein, as each such sub-combination of chemical groups and each such sub-combination are individually and clearly disclosed herein.

[0463] Definition of Chemical Substance

[0464] The term "alkyl" refers to a straight or branched monovalent hydrocarbon group. The term "alkylene" refers to a straight or branched divalent hydrocarbon group. In some embodiments, it may be advantageous to limit the number of atoms in "alkyl" or "alkylene" to a specific atomic range, such as C1-C 20 Alkyl or C1-C 20 Alkylene, C1-C 12 Alkyl or C1-C 12Alkylene, or C1-C6 alkyl or C1-C6 alkylene. Examples of alkyl include: methyl (Me), ethyl (Et), n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl (tBu), pentyl, isopentyl, tert-pentyl, hexyl, isohexyl, and groups that will be considered equivalent to any of the foregoing examples in view of those of ordinary skill and the teachings provided herein. Examples of alkylene include methylene (-CH2-), ethylene ((-CH2-)2), n-propylene ((-CH2-)3), isopropylene ((-C(H)(CH3)CH2-)), n-butylene ((-CH2-)4), etc. It should be understood that an alkyl or alkylene group may be unsubstituted or substituted as described herein. An alkyl or alkylene group may be substituted with any substituent in the various embodiments described herein, including one or more of such substituents.

[0465] The term "alkenyl" refers to a straight or branched monovalent hydrocarbon radical having one or more double bonds. The term "alkenylene" refers to a straight or branched divalent hydrocarbon radical having one or more double bonds. In some embodiments, it may be advantageous to limit the number of atoms in "alkenyl" or "alkenylene" to a specific atomic range, such as C2-C 20 Alkenyl or C2-C 20 Alkenylene, C2-C 12 Alkenyl or C2-C 12 Alkenylene or C2-C6 alkenyl or C2-C6 alkenyl. Examples of alkenyl groups include ethenyl / vinyl, allyl, and but-3-en-1-yl. Examples of alkenyl groups include ethenylene / vinylene (-CH=CH-), n-propenylene (-CH=CHCH2-), isopropenylene (-CH=CHCH3)-), and the like. Cis and trans isomers and mixtures thereof are included within this term. It should be understood that an alkenyl or alkenylene group may be unsubstituted or substituted as described herein. An alkenyl or alkenylene group may be substituted with any substituent in the various embodiments described herein, including one or more of such substituents.

[0466] The term "alkynyl" refers to a straight or branched monovalent hydrocarbon radical having one or more triple bonds. The term "alkynylene" refers to a straight or branched divalent hydrocarbon radical having one or more triple bonds. In some embodiments, it may be advantageous to limit the number of atoms in "alkynyl" or "alkynylene" to a specific atomic range, such as C2-C 20 Alkynyl or C2-C 20 Alkynylidene, C2-C 12 Alkynyl or C2-C 12Alkyne, or C2-C6 alkynyl or C2-C6 alkynyl. Examples of alkynyl include ethynyl (-C≡CH) and propargyl (-CH2C≡CH), but-3-yn-1,4-diyl (-C≡C-CH2CH2-), etc. It should be understood that the alkynyl or alkynylene group can be unsubstituted or substituted as described herein. The alkynyl or alkynylene group can be substituted with any substituent in the various embodiments described herein, including one or more of such substituents.

[0467] The term "cycloalkyl" refers to a saturated or partially saturated monocyclic or polycyclic monovalent carbocyclic ring. The term "cycloalkylene" refers to a saturated or partially saturated monocyclic or polycyclic divalent carbocyclic ring. In some embodiments, it may be advantageous to limit the number of atoms in "cycloalkyl" or "cycloalkylene" to a specific atomic range, for example, having 3 to 12 ring atoms. Polycyclic carbocyclic rings include fused, bridged, and spiro-connected polycyclic ring systems. Illustrative examples of cycloalkyl include monovalent groups of the following entities, while cycloalkylene includes divalent groups of the following entities, in the form of appropriate bonding moieties:

[0468]

[0469] Specifically, the cyclopropyl moiety can be represented by the structural formula Specifically, the cyclopropylene moiety can be represented by the structural formula It should be understood that the cycloalkyl or cycloalkylene group can be unsubstituted or substituted as described herein. The cycloalkyl or cycloalkylene group can be substituted with any substituent in the various embodiments described herein, including one or more of such substituents.

[0470] The term "halogen" or "halo" refers to chlorine, fluorine, bromine or iodine.

[0471] The term "haloalkyl" refers to an alkyl group having one or more halo substituents. Examples of haloalkyl groups include -CF3, -(CH2)F, -CHF2, -CH2Br, -CH2CF3, and -CH2CH2F. The term "haloalkylene" refers to an alkyl group having one or more halo substituents. Examples of haloalkyl groups include -CF2-, -C(H)(F)-, -C(H)(Br)-, -CH2CF2-, and -CH2C(H)(F)-.

[0472] The term "aryl" refers to a monovalent all-carbon monocyclic or fused-ring polycyclic group having a completely conjugated π electron system. The term "arylene" refers to a divalent all-carbon monocyclic or fused-ring polycyclic group having a completely conjugated π electron system. In some embodiments, it may be advantageous to limit the number of atoms in the "aryl" or "arylene" group to a specific atomic range, such as a monovalent all-carbon monocyclic or fused-ring polycyclic group having 6 to 14 carbon atoms (C6-C 14 aryl), a monovalent all-carbon monocyclic or condensed-ring polycyclic group having 6 to 10 carbon atoms (C6-C10 aryl), a divalent all-carbon monocyclic or condensed-ring polycyclic group having 6 to 14 carbon atoms (C6-C 14 arylene) and a divalent all-carbon monocyclic or condensed-ring polycyclic group having 6 to 10 carbon atoms (C6-C 10 Examples of aryl groups include, but are not limited to, phenyl, naphthyl, and anthracenyl. Examples of arylene groups include, but are not limited to, phenylene, naphthylene, and anthracenyl. It should be understood that an aryl or arylene group may be unsubstituted or substituted as described herein. An aryl or arylene group may be substituted with any substituent in the various embodiments described herein, including one or more of such substituents.

[0473] The term "heterocycloalkyl" refers to a saturated or partially saturated monovalent monocyclic or polycyclic structure with one or more non-carbon ring atoms. The term "heterocycloalkylene" refers to a saturated or partially saturated divalent monocyclic or polycyclic structure with one or more non-carbon ring atoms. In some embodiments, it may be advantageous to limit the number of atoms in "heterocycloalkyl" or "heterocycloalkylene" to a specific ring atom range, such as 3 to 12 ring atoms (3 to 12 members), or 3 to 7 ring atoms (3 to 7 members), or 3 to 6 ring atoms (3 to 6 members), or 4 to 6 ring atoms (4 to 6 members), 5 to 7 ring atoms (5 to 7 members), or 4 to 10 ring atoms (4 to 10 members). In some embodiments, it may be advantageous to limit the number and type of ring heteroatoms in "heterocycloalkyl" or "heterocycloalkylene" to a specific heteroatom range or type, such as 1 to 5 ring heteroatoms selected from nitrogen, oxygen and sulfur. Polycyclic ring systems include fused, bridged, and spiro systems. The ring structure may optionally contain an oxo or imino group on a carbon ring member or up to two oxo groups on a sulfur ring member. Illustrative examples of heterocycloalkyl groups include monovalent radicals of the following entities, while heterocycloalkylene groups include divalent radicals of the following entities, in the form of appropriate bonding moieties:

[0474]

[0475]

[0476] The three-membered heterocyclic ring may contain at least one heteroatom ring atom, wherein the heteroatom ring atom is sulfur, oxygen or nitrogen. The limiting examples of the three-membered heterocyclic group include the monovalent and divalent groups of oxirane, azetidine and thiirane. The four-membered heterocyclic ring may contain at least one heteroatom ring atom, wherein the heteroatom ring atom is sulfur, oxygen or nitrogen. The limiting examples of the four-membered heterocyclic group include the monovalent and divalent groups of azetidine (azitidine), oxetane (oxtenane) and thiirane (thietane). The five-membered heterocyclic ring may contain up to four heteroatom ring atoms, wherein (a) at least one ring atom is oxygen and sulfur, and zero, one, two or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of five-membered heterocyclic groups include monovalent and divalent groups: pyrrolidine, tetrahydrofuran, 2,5-dihydro-1H-pyrrole, pyrazolidine, thiazolidine, 4,5-dihydro-1H-imidazole, dihydrothiophen-2(3H)-one, tetrahydrothiophene 1,1-dioxide, imidazolidin-2-one, pyrrolidin-2-one, dihydrofuran-2(3H)-one, 1,3-dioxolane-2-one and oxazolidin-2-one. The six-membered heterocyclic ring may contain up to four heteroatom ring atoms, wherein (a) at least one ring atom is oxygen and sulfur, and zero, one, two or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of six-membered heterocyclic groups include monovalent or divalent radicals of each of piperidine, morpholine, 4H-1,4-thiazine, 1,2,3,4-tetrahydropyridine, piperazine, 1,3-oxazacyclohexan-2-one, piperazin-2-one, thiomorpholine, and thiomorpholine 1,1-dioxide. "Heterobicyclic" is a fused bicyclic ring system comprising one heterocyclic ring fused to a cycloalkyl group or another heterocyclic ring.

[0477] It should be understood that the heterocycloalkyl or heterocycloalkylene group can be unsubstituted or substituted as described herein. The heterocycloalkyl or heterocycloalkylene group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0478] The term "heteroaryl" refers to a monovalent monocyclic, fused bicyclic or fused polycyclic aromatic heterocyclic ring (a ring structure having ring atoms or members selected from carbon atoms and up to four heteroatoms selected from nitrogen, oxygen and sulfur) that is completely unsaturated and each heterocyclic ring has 3 to 12 ring atoms. The term "heteroarylidene" refers to a divalent monocyclic, fused bicyclic or fused polycyclic aromatic heterocyclic ring (a ring structure having ring atoms or members selected from carbon atoms and up to four heteroatoms selected from nitrogen, oxygen and sulfur) that each heterocyclic ring has 3 to 12 ring atoms. In some embodiments, it may be advantageous to limit the number of ring atoms in "heteroaryl" or "heteroarylidene" to a specific atomic number range, such as a 5- to 10-membered heteroaryl or a 5- to 10-membered heteroarylidene. In some cases, a 5- to 10-membered heteroaryl group may be a monocyclic or fused bicyclic ring having 5 to 10 ring atoms, wherein at least one ring atom is a heteroatom, such as N, O or S. In some cases, a 5- to 10-membered heteroarylene group may be a monocyclic or fused bicyclic ring having 5 to 10 ring atoms, wherein at least one ring atom is a heteroatom, such as N, O, or S. The ring structure may optionally contain an oxo or imino group on a carbon ring member or up to two oxo groups on a sulfur ring member. Illustrative examples of 5- to 10-membered heteroarylene groups include monovalent radicals of the following entities, while examples of 5- to 10-membered heteroarylene groups include divalent radicals of the following entities, in the form of appropriate bonding moieties:

[0479]

[0480] In some embodiments, a "monocyclic" heteroaryl group can be an aromatic five-membered or six-membered heterocycle. A five-membered heteroaryl or heteroarylide group can contain up to four heteroatom ring atoms, wherein (a) at least one ring atom is oxygen and sulfur, and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of five-membered heteroaryls include monovalent groups of furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, pyrazole, imidazole, oxadiazole, thiadiazole, triazole, or tetrazole. Non-limiting examples of five-membered heteroarylide groups include divalent groups of furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, pyrazole, imidazole, oxadiazole, thiadiazole, triazole, or tetrazole. A six-membered heteroaryl or heteroarylidene group may contain up to four heteroatom ring atoms, wherein (a) at least one ring atom is oxygen and sulfur, and zero, one, two, or three ring atoms are nitrogen, or (b) zero ring atoms are oxygen or sulfur and up to four ring atoms are nitrogen. Non-limiting examples of six-membered heteroaryls include the following monovalent groups: pyridine, pyrazine, pyrimidine, pyridazine, or triazine. Non-limiting examples of six-membered heteroarylidene groups include divalent groups of pyridine, pyrazine, pyrimidine, pyridazine, or triazine. "Bicyclic heteroaryl" or "bicyclic heteroarylidene" is a fused bicyclic ring system comprising a heteroaromatic ring fused to a phenyl or another heteroaromatic ring. Non-limiting examples of bicyclic heteroaryl groups include monovalent radicals of quinoline, isoquinoline, quinazoline, quinoxaline, 1,5-naphthyridine, 1,8-naphthyridine, isoquinolin-3(2H)-one, thieno[3,2-b]thiophene, 1H-pyrrolo[2,3-b]pyridine, 1H-benzo[d]imidazole, benzo[d]oxazole, and benzo[d]thiazole. Non-limiting examples of bicyclic heteroarylene groups include divalent radicals of quinoline, isoquinoline, quinazoline, quinoxaline, 1,5-naphthyridine, 1,8-naphthyridine, isoquinolin-3(2H)-one, thieno[3,2-b]thiophene, 1H-pyrrolo[2,3-b]pyridine, 1H-benzo[d]imidazole, benzo[d]oxazole, and benzo[d]thiazole.

[0481] Specifically, the pyrazolyl moiety can be represented by the structural formula Specifically, an example of a pyrazolylene moiety can be represented by the structural formula Describe.

[0482] It should be understood that the heteroaryl or heteroarylene group can be unsubstituted or substituted as described herein. The heteroaryl or heteroarylene group can be substituted with any of the substituents in the various embodiments described herein, including one or more of such substituents.

[0483] The term "oxo" refers to a carbonyl oxygen group. For example, an oxo-substituted cyclopentyl group is cyclopentanone.

[0484] The term "substituted" means that the specified group or moiety bears one or more substituents. The term "unsubstituted" means that the specified group bears no substituents. When the term "substituted" is used to describe a structural system, substitution is intended to occur at any valency-allowed position on the system. In some embodiments, "substituted" means that the specified group or moiety bears one, two, or three substituents. In other embodiments, "substituted" means that the specified group or moiety bears one or two substituents. In other embodiments, "substituted" means that the specified group or moiety bears one substituent.

[0485] Any formula depicted herein is intended to represent the compound of the formula as well as certain variations or forms. For example, a formula given herein is intended to include racemic forms or one or more enantiomers, diastereomers, or geometric isomers, or mixtures thereof. Additionally, any formula given herein is intended to refer to hydrates, solvates, or polymorphs of such compound, or mixtures thereof.

[0486] Any formula given herein is also intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. Isotopically labeled compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds also include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, for example, respectively. 2 H. 3 H. 11 C. 13 C. 14 C. 15 N. 18 O. 17 O. 31 P. 32 P. 35 S. 18 F. 36 Cl and 125 I. Such isotopically labeled compounds are suitable for metabolic studies (preferably using 14 C); reaction kinetic studies (using e.g. 2 H or 3 H); detection or imaging techniques [e.g., positron emission tomography (PET) or single photon emission computed tomography (SPECT)], including drug or substrate tissue distribution analysis; or radiotherapy applied to the patient. In addition, the use of, for example, deuterium (i.e. 2H) can afford certain therapeutic advantages resulting from greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements. Isotopically labeled compounds and prodrugs thereof disclosed herein can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below, by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

[0487] Certain chemical entities of formula (I)-(XII) can be depicted in two or more tautomeric forms. Any and all alternative tautomers are included within the scope of these formulas, and no inference should be made as to whether the chemical entity exists in the drawn tautomeric form. It should be understood that certain chemical entities described herein can exist in different tautomeric forms. One skilled in the art will readily appreciate that, due to rapid interconversion, tautomers can generally be considered to be the same compound. Examples of tautomers include, but are not limited to, enol-keto tautomers, amine-imine tautomers, and the like.

[0488]

[0489] Special term "(atom) i -(atom) j "(wherein j>i) when applied to a class of substituents herein means that each of the number of atomic members from i to j (inclusive) is independently realized in the disclosed embodiments. For example, the term C 1- C3 independently refers to the embodiment with one carbon member (C1), the embodiment with two carbon members (C2), and the embodiment with three carbon members (C3).

[0490] Where more than one of such possibilities is permitted, any reference herein to a disubstituent is intended to encompass each such possibility. For example, reference to a disubstituent -JK-, where J≠K, refers herein to such a disubstituent having J attached to the first substituted member and K attached to the second substituted member, and it also refers to such a disubstituent having J attached to the second member and K attached to the first substituted member.

[0491] It will be understood that some of the compounds described herein include one or more positions that can exist as stereoisomers. For example, some of the compounds described herein include one or more carbon atoms that can exist in one or more stereoisomeric arrangements. It will be understood that carbon atoms that can exist in stereoisomeric arrangements depicted without showing any stereoisomeric arrangements include each of the disclosed possible stereoisomeric arrangements. For example, a carbon atom having four groups that can be prioritized according to the Cahn-Ingold Prelog rules known to those skilled in the art will be understood herein to describe the structure presented below as having no specific stereochemical definition, and also describes two possible stereoisomers (S) and (R) as shown below.

[0492]

[0493] According to the Cahn-Ingold Prelog rule, R a >R b >R c >R d .

[0494] The present disclosure also includes pharmaceutically acceptable salts of compounds represented by Formulas (I)-(XII), preferably, the compounds described above and the specific compounds exemplified herein, and pharmaceutical compositions containing such salts, and methods of using such salts.

[0495] "Pharmaceutically acceptable salts" are intended to mean non-toxic, biotolerable, or otherwise biologically suitable salts of the free acids or bases of the compounds represented herein that are suitable for administration to a subject. See generally SM Berge et al., "Pharmaceutical Salts," J. Pharm. Sci., 1977, 66, 1-19. Preferred pharmaceutically acceptable salts are those that are pharmacologically effective and suitable for use in contact with the tissues of a subject without undue toxicity, irritation, or allergic reaction. The compounds described herein may have a sufficiently acidic group, a sufficiently basic group, both types of functional groups, or more than one of each type, and thus react with a variety of inorganic or organic bases and inorganic and organic acids to form pharmaceutically acceptable salts.

[0496] Examples of pharmaceutically acceptable salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, hydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, octanoates, acrylates, formates, isobutyrates, hexanoates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne- The pharmaceutically acceptable salts of the present invention include benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methylsulfonate, propylsulfonate, benzenesulfonate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, gamma-hydroxybutyrate, glycolate, tartrate, and mandelate. A list of other suitable pharmaceutically acceptable salts is found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985.

[0497] For compounds of formula (I)-(XII) containing a basic nitrogen group, pharmaceutically acceptable salts can be prepared by any suitable method available in the art, for example, by treating the free base with an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, nitric acid, boric acid, phosphoric acid, or the like; or with an organic acid such as acetic acid, phenylacetic acid, propionic acid, stearic acid, lactic acid, ascorbic acid, maleic acid, hydroxymaleic acid, isethionic acid, succinic acid, valeric acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, oleic acid, palmitic acid, benzoic ... Cinnamic acid, pyranosidic acid (e.g., glucuronic acid or galacturonic acid), α-hydroxy acid (e.g., mandelic acid, citric acid, or tartaric acid), amino acid (e.g., aspartic acid or glutamic acid), aromatic acid (e.g., benzoic acid, 2-acetoxybenzoic acid, naphthoic acid, or cinnamic acid), sulfonic acid (e.g., laurylsulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, or ethanesulfonic acid); or any compatible mixture of acids, such as those given as examples herein; and any other acids and mixtures thereof that are considered equivalents or acceptable substitutes in view of the general level of skill in the art.

[0498] The present disclosure further relates to pharmaceutically acceptable prodrugs of formula (I)-(XII) compounds, and methods of treating using such pharmaceutically acceptable prodrugs. The term "prodrug" means a precursor of a given compound, which, after being administered to an individual, produces the compound in vivo via a chemical or physiological process (such as solvolysis or enzymatic cleavage) or under physiological conditions (for example, the prodrug is converted into a formula (I)-(XII) compound when physiological pH is reached). "Pharmaceutically acceptable prodrug" is nontoxic, biologically tolerable, and otherwise biocompatible with a prodrug administered to an individual. Illustrative procedures for selecting and preparing suitable prodrug derivatives are described in, for example, "Prodrug Design (Design of Prodrugs)", edited by H. Bundgaard, Elsevier (Elsevier), 1985.

[0499] The present disclosure also relates to pharmaceutically active metabolites of compounds of Formula (I)-(XII), and the use of such metabolites in the methods of the present disclosure. "Pharmaceutically active metabolite" means a pharmacologically active product of in vivo metabolism of a compound of Formula (I)-(XII) or a salt thereof. Prodrugs and active metabolites of a compound can be determined using conventional techniques known or available in the art. See, e.g., Bertolini et al., J. Med. Chem. 1997, 40, 2011-2016; Shan et al., J. Pharm. Sci. 1997, 86(7), 765-767; Bagshawe, Drug Dev. Res. 1995, 34, 220-230; Bodor, Adv. Drug Res. 1984, 13, 255-331; Bundgaard, Design of Prodrugs (Elsevier Press, 1985); and Larsen, Design and Application of Prodrugs, Drug Design and Development) (Krogsgaard-Larsen et al., eds., Harwood Academic Publishers, 1991).

[0500] Representative Examples

[0501] In some embodiments, the present disclosure provides a compound of Formula I or a pharmaceutically acceptable salt thereof,

[0502]

[0503] where R 1 、R 2 、R 3 、R 4 , A, B, L, m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0504] In some embodiments, the present disclosure provides a compound of Formula II or a pharmaceutically acceptable salt thereof,

[0505]

[0506] where R 1 、R 2 、R 3 、R 4 , A, B, L, Y, m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0507] In some embodiments, the present disclosure provides a compound of formula III or a pharmaceutically acceptable salt thereof,

[0508]

[0509] where R 1 、R 2 、R 3 、R 4 ,A,B,L,Z,Z 1 , m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0510] In some embodiments, the present disclosure provides a compound of formula IV or a pharmaceutically acceptable salt thereof,

[0511]

[0512] where R 2 、R 3 、R 4 , A, B, L, X 1 、X 2 、X 3 , Z, Z 1 , m, n, p, and q are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0513] In some embodiments, the present disclosure provides a compound of formula V or a pharmaceutically acceptable salt thereof,

[0514]

[0515] where R 1 、R 2 、R 3 、R 4 , A, B, L, m, n and p are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0516] In some embodiments, the present disclosure provides a compound of Formula VI or a pharmaceutically acceptable salt thereof,

[0517]

[0518] where R 1 、R 2 、R 3 、R 4 , A, B, L, Y, m, n and p are as described herein. In some embodiments of this aspect, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) pDoes not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0519] In some embodiments, the present disclosure provides a compound of Formula VII or a pharmaceutically acceptable salt thereof,

[0520]

[0521] where R 1 、R 2 、R 3 、R 4 ,A,B,L,Z,Z 1 , m, n, and p are as described herein. In some embodiments of this aspect, (L) p Does not contain -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0522] In some embodiments, the present disclosure provides a compound of Formula VIII or a pharmaceutically acceptable salt thereof,

[0523]

[0524] where R 2 、R 3 、R 4 , A, B, L, X 1 、X 2 、X 3 , Z, Z 1 , m, n, and p are as described herein. In some embodiments of this aspect, (L) p Does not contain -NR directly covalently linked to ring A 5 C(O)-. In some embodiments of this aspect, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0525] In some embodiments, the present disclosure provides a compound of Formula IX or a pharmaceutically acceptable salt thereof,

[0526]

[0527] where R 1 、R 2 、R 3 、R 4 、R 6 、R7 , A, B, m, n, p1 and q are as described herein.

[0528] In some embodiments, the present disclosure provides a compound of formula X or a pharmaceutically acceptable salt thereof,

[0529]

[0530] where R 1 、R 2 、R 3 、R 4 、R 6 、R 7 ,A,B,Z,Z 1 , m, n, p1 and q are as described herein.

[0531] In some embodiments, the present disclosure provides a compound of Formula XI or a pharmaceutically acceptable salt thereof,

[0532]

[0533] where R 1 、R 2 、R 3 、R 4 、R 6 、R 7 , A, B, X 1 、X 2 、X 3 、Y 1 、Y 2 、Y 3 , Z, Z 1 , p1 and q are as described herein.

[0534] In some embodiments, the present disclosure provides a compound of Formula XII or a pharmaceutically acceptable salt thereof,

[0535]

[0536] where R 3 、R 4 、R 6 、R 7 , A, B, X 1 、X 2 、X 3 、Y 1 、Y 2 、Y 3 , Z, Z 1 and q as described herein.

[0537] In some embodiments, Ring B is a 5- to 10-membered heteroarylene group or a C6-C 10In some embodiments, Ring B is a monocyclic or bicyclic C6-C 10 Arylene, or a monocyclic or bicyclic 5- to 10-membered heteroarylene.

[0538] In some embodiments, Ring A is a 5- to 10-membered heteroarylene. In some embodiments, Ring A is a 5- or 6-membered heteroarylene. In some embodiments, Ring A is a 5-membered heteroarylene. In some embodiments, Ring A is a 6-membered heteroarylene. In some embodiments, Ring A is a fused bicyclic 8- to 10-membered heteroarylene.

[0539] In some embodiments, Ring A is a 5- to 10-membered heteroarylene, such as a monocyclic 5- or 6-membered heteroarylene or a bicyclic 8- to 10-membered heteroarylene, wherein each hydrogen atom in the 5- to 10-membered heteroarylene is independently optionally replaced by R as described herein. 1 Substitution: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR aS(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0540] In some embodiments, ring A is pyrrolylene, isoxazolylene, isothiazolylene, pyrazolylene or imidazolylene, wherein each hydrogen atom in pyrrolylene, isoxazolylene, isothiazolylene, pyrazolylene and imidazolylene is independently optionally replaced by R 1 Substitution: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a Rb 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c Rd 、 -OS(O)2NR c R d 、 -SR c 、 -S(O)R c 、 -S(O)2R c 、 -S(O)NR c R d 、 -S(O)2NR c R d 、 -NR c R d 、 -NR c 、 -NR d 、 -N(C(O)R c )(C(O)R d 、 -NR c 、 -NR d 、 -NR c 、 -NR c R d 、 -NR c 、 -NR c R d 、 -NR c 、 -NR d 、 -NR c 、 -NR d 、 -NR c 、 -NR c R d 、 -NR c 、 -NR c R d 、 -C(O)R c 、 -C(O)OR c 、 -C(O)NR c R d 、 -C(=N)NR c R d 、 -PR c R d 、 -P(O)R c R d 、 -P(O)2R c R d 、 -P(O)NR c R d [[ID=9x]] 、 -P(O)2NR c R d 、 -P(O)OR c 、 -P(O)2OR c 、 -CN or -NO2.

[0541] In some embodiments, Ring A is pyridinylene, pyrazinylene, pyrimidinylene, or pyridazinylene, wherein each hydrogen atom in the pyridinylene, pyrazinylene, pyrimidinylene, or pyridazinylene group is independently optionally replaced by R 1 Substitution: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR aR b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)Rc 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0542] In some embodiments, Ring A is a 5- to 10-membered heteroarylene, such as a monocyclic 5- or 6-membered heteroarylene or a bicyclic 8- to 10-membered heteroarylene, wherein the 5- to 10-membered heteroarylene is optionally substituted with 1, 2, 3, 4, or 5 R 1 (m R 1 ) substituted, said R 1 Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN and -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NRc R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2. In some embodiments, the two R 1 Together with the atoms to which they are attached, they form a C3-C6 cycloalkyl group, a 3-membered to a 7-membered heterocycloalkyl group, wherein when two R 1 Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when taken together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NRe R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0543] In some embodiments, Ring A is pyridinylene, pyrazinylene, pyrimidinylene, or pyridazinylene, each of which is optionally substituted with 1, 2, 3, 4, or 5 R 1 (m R 1 ) substituted, said R 1Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)ORa 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c Rd 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c In some embodiments, Ring A is pyridinylene, pyrazinylene, pyrimidinylene, or pyridazinylene, wherein the two R 1 Together with the atoms to which they are attached, they form a C3-C6 cycloalkyl group, a 3-membered to a 7-membered heterocycloalkyl group, wherein when two R 1 Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when taken together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NRe S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0544] In some embodiments, Ring A is pyrrolylene, isoxazolylene, isothiazolylene, pyrazolylene, or imidazolylene, each of which is optionally substituted with 1, 2, 3, 4, or 5 R 1 (m R 1 ) substituted, said R 1 Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)Rb 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN and -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c Rd 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2. In some embodiments, as described herein, the two R 1 Together with the atoms to which they are attached, they form a C3-C6 cycloalkyl group, a 3-membered to a 7-membered heterocycloalkyl group, wherein when two R 1 Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when taken together is independently optionally substituted with: -OR e 、-OC(O)R e、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0545] In some embodiments, Ring A has the formula:

[0546]

[0547] Wherein Y is a single bond, a double bond, -O-, -S-, =C(H)-, =C(R 1 )-、-N(H)-、-N(R 1 )-or=N-, each represents the covalent attachment point, and R 1 and m are as described herein. In some embodiments, Ring A is a 5- to 10-membered heteroarylene group. In some embodiments, Ring A is a 5- or 6-membered heteroarylene group.

[0548] In some embodiments, Ring A has the formula:

[0549]

[0550] Where Z is Where * is the same as (L) p The covalent connection point of Z 1 The covalent attachment point, represents the point of covalent attachment to a ring atom of Ring A, and Indicates that at the connection point** and The situation where one bond between them is a single bond and one bond is a double bond; Z 1 for Among them, *** is The covalent connection point of , **** is the covalent connection point with Z, represents the point of covalent attachment to a ring atom of Ring A, and Indicates the connection point **** with The situation where one bond between them is a single bond and one bond is a double bond, and the premise is that Z and Z 1 In some embodiments, Ring A is a 5- to 10-membered heteroarylene group. In some embodiments, Ring A is a 5- or 6-membered heteroarylene group.

[0551] In some embodiments, Ring A has the formula:

[0552]

[0553] in

[0554] X 1 、X 2 and X 3 are independently -O-, -S-, =C(H)-, =C(R 1 )-、-N(H)-、-N(R 1 )- or = N-, provided that X 1 、X 2 and X 3 At least one of them is not =C(H)- or =C(R 1)-;

[0555] Z is Where * is the same as (L) p The covalent connection point of Z 1 The covalent attachment point, represents the point of covalent attachment to a ring atom of Ring A, and Indicates that at the connection point** and The situation where one bond between them is a single bond and one bond is a double bond; Z 1 for Among them, *** is The covalent connection point of , **** is the covalent connection point with Z, represents the point of covalent attachment to a ring atom of Ring A, and Indicates the connection point **** with The situation where one bond between them is a single bond and one bond is a double bond, and the premise is that Z and Z 1 In some embodiments, Ring A is a 5- to 10-membered heteroarylene group. In some embodiments, Ring A is a 5- or 6-membered heteroarylene group.

[0556] In some embodiments, m is 0, 1, 2, 3, or 4. In some embodiments, m is 0, 1, 2, or 3. In some embodiments, m is 0, 1, or 2. In some embodiments, m is 0 or 1. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

[0557] In some embodiments, Ring A is a 5- to 10-membered heteroarylene selected from the group consisting of:

[0558]

[0559]

[0560] Each of these Indicates the point of covalent attachment.

[0561] In some embodiments, Ring A is a 5- or 6-membered heteroarylene selected from the group consisting of:

[0562]

[0563]

[0564] Each of these represents a covalent attachment point, and each R 1 Independently as described herein.

[0565] In some embodiments, Ring A is a 5- to 10-membered heteroarylene selected from the group consisting of:

[0566]

[0567] Each of these Indicates the point of covalent attachment.

[0568] In some embodiments, Ring A is a 5- or 6-membered heteroarylene selected from the group consisting of:

[0569]

[0570] Each of these represents a covalent attachment point, and each R 1 As described herein.

[0571] In some embodiments, each R 1 are independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NRa R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NRc C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0572] In some embodiments, each R 1 are independently deuterium, halogen, C1-C6 alkyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, -CN, -OR a or -C(O)NR a R b , wherein each hydrogen atom in C1-C6 alkyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c Rd 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0573] In some embodiments, each R 1are independently deuterium, halogen, C1-C6 alkyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, or -C(O)NR a R b , wherein each hydrogen atom in C1-C6 alkyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NRc R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0574] In some embodiments, two R 1 Together with the atoms to which they are attached, they are optionally combined to form a C3-C6 cycloalkyl, a 3-membered to a 7-membered heterocycloalkyl, wherein when two R 1 Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when taken together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NRe S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0575] In some embodiments, Ring A is a 5- to 10-membered heteroarylene selected from the group consisting of:

[0576]

[0577]

[0578]

[0579]

[0580] Each of these Indicates the point of covalent attachment.

[0581] In some embodiments, Ring A is a 5- or 6-membered heteroarylene selected from the group consisting of:

[0582]

[0583]

[0584] Each of these Indicates the point of covalent attachment.

[0585] In some embodiments, Ring A is a monocyclic or bicyclic C6-C 10 In some embodiments, Ring A is a monocyclic C6-C 10 In some embodiments, Ring A is a bicyclic C6-C 10 Arylene.

[0586] In some embodiments, Ring A is C6-C 10 Monocyclic or bicyclic arylene, wherein C6-C10 Each hydrogen atom in the monocyclic or bicyclic arylene group is independently optionally substituted by R 1 Substitution: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NRa R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)ORc 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0587] In some embodiments, Ring A is phenylene or naphthylene, wherein each hydrogen atom in the phenylene or naphthylene group is independently optionally replaced by R 1 Substitution: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2Rb 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NRc C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0588] In some embodiments, Ring A is C6-C 10 Monocyclic or bicyclic arylene, each of which is optionally substituted with 1, 2, 3, 4 or 5 R 1 (m R 1 ) substituted, said R 1 Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d )、-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)ORc 、-P(O)2OR c , -CN and -NO2.

[0589] In some embodiments, Ring A is phenylene or naphthylene, each of which is optionally substituted with 1, 2, 3, 4, or 5 R 1 (m R 1 ) substituted, said R 1 Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a Rb 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NRc S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0590] In some embodiments, Ring A is C6-C 10 In some embodiments, Ring A is phenylene, and m is as defined herein.

[0591] In some embodiments, m is 0, 1, 2, 3, or 4. In some embodiments, m is 0, 1, 2, or 3. In some embodiments, m is 0, 1, or 2. In some embodiments, m is 0 or 1. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

[0592] In some embodiments, each R 1 are independently methyl, ethyl, F, Cl, Br, -CN, Each of these In some embodiments, R 1 is methyl, ethyl, F, Cl, Br or Each of these In some embodiments, ring A is phenylene, n is 1, and R 1 is methyl, ethyl, F, Cl, Br or Each of these Indicates the point of covalent attachment.

[0593] In some embodiments, Ring A is phenylene, m is 1, and R 1 Methyl, ethyl, F, Cl, Br, -CN,

[0594] Each of these Indicates the point of covalent attachment.

[0595] In some embodiments, Ring A has the formula:

[0596]

[0597] Each of these In some embodiments, Ring A is a Ring A having the formula:

[0598]

[0599] Each of these Indicates the point of covalent attachment.

[0600] In some embodiments, Ring B is a 5-membered heteroarylene.

[0601] In some embodiments, Ring B is pyrrolylene, isoxazolylene, isothiazolylene, pyrazolylene, or imidazolylene, wherein each hydrogen atom in pyrrolylene, isoxazolylene, isothiazolylene, pyrazolylene, and imidazolylene is independently optionally replaced by R 2 Substitution: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NRa C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NRc R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[0602] In some embodiments, Ring B is pyrrolylene, isoxazolylene, isothiazolylene, pyrazolylene, or imidazolylene, each of which is optionally substituted with 1, 2, 3, 4, or 5 R 2 (n R 2 ) substituted, said R 2 Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a, -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c Rd 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN and -NO2.

[0603] In some embodiments, n is 0, 1, 2, 3, or 4. In some embodiments, n is 0, 1, 2, or 3. In some embodiments, n is 0, 1, or 2. In some embodiments, n is 0 or 1. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4.

[0604] In some embodiments, Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0605]

[0606] Each of these Indicates the point of covalent attachment.

[0607] In some embodiments, Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0608]

[0609] Each of these represents a covalent attachment point, and each R 2 Independently as described herein.

[0610] In some embodiments, Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0611]

[0612]

[0613] Each of these Indicates the point of covalent attachment.

[0614] In some embodiments, Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0615]

[0616] Each of these represents a covalent attachment point, and each R 2 Independently as described herein.

[0617] In some embodiments, each R 2 are independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a Rb 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NRc R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2. In some embodiments, each R 2 is independently deuterium or C1-C6 alkyl, wherein each hydrogen atom in the C1-C6 alkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2. In some embodiments, the two R 2 Together with the atoms to which they are attached, they are optionally combined to form a C3-C6 cycloalkyl, a 3-membered to a 7-membered heterocycloalkyl, wherein when two R 1 Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when taken together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0618] In some embodiments, Ring B is a 5-membered heteroarylene selected from the group consisting of:

[0619]

[0620] Each of these Indicates the point of covalent attachment.

[0621] In some embodiments, q is 0, 1, or 2. In some embodiments, q is 0 or 1. In some embodiments, q is 0. In some embodiments, q is 1.

[0622] In some embodiments, R 3 is deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)Ra 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c Rd 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2. In some embodiments, R 3 In some embodiments, R 3 In some embodiments, two R 3 Together with the atoms to which they are attached, they are optionally combined to form a C3-C6 cycloalkyl, a 3-membered to a 7-membered heterocycloalkyl, wherein when two R 1 Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when taken together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)Re 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0623] In some embodiments, R 4 H, deuterium, C1-C6 alkyl, -C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-P(O)2R c R d 、-P(O)2NR c R d 、-P(O)2OR c or -S(O)2OR c In some embodiments, R 4 is H or deuterium. In some embodiments, R 4 is H. In some embodiments, R 4 is a C1-C6 alkyl group. In some embodiments, R 4 It is methyl or ethyl.

[0624] In some embodiments, each R 5 If present, independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl or 5- to 10-membered heteroaryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in an aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with: -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d )、-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c, -CN or -NO2. In some embodiments, each R 5 are independently H, methyl, ethyl, -C(O)CH3 or -C(O)CH2CH3; or R 5 With R 6 The groups are combined to form a 3- to 7-membered heterocycloalkyl group.

[0625] In some embodiments, each R 5 If present, independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, -C(O)R a , 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl or 5- to 10-membered heteroaryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in an aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with: -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2. In some embodiments, each R 5 are independently H, methyl, ethyl, -C(O)CH3 or -C(O)CH2CH3; or R 5 With R 6 The groups are combined to form a 3- to 7-membered heterocycloalkyl group.

[0626] In some embodiments, each L is independently -C(R 6 )(R 7 )-, -C(O)-, -O- or -N(R 5 )-, provided that (L) p Does not contain -OO- or -ON(R 5 )-key, and (L) p The point of covalent attachment to Ring A does not form an -NN- or -ON- bond.

[0627] In some embodiments, p is 3, 4, 5, 6, 7, 8, or 9. In some embodiments, p is 4, 5, 6, 7, 8, or 9. In some embodiments, p is 4, 5, 6, 7, or 8. In some embodiments, p is 4, 5, 6, or 7. In some embodiments, p is 5, 6, 7, or 8. In some embodiments, p is 5, 6, or 7. In some embodiments, p is 3, 4, 5, 6, or 7. In some embodiments, p is 3, 4, 5, or 6. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 5. In some embodiments, p is 6. In some embodiments, p is 7. In some embodiments, p is 8. In some embodiments, p is 9.

[0628] In some embodiments, p1 is 2, 3, or 4. In some embodiments, p1 is 2. In some embodiments, p1 is 3. In some embodiments, p1 is 4.

[0629] In some embodiments, -(L) p -Contains-CR 6 R 7 -O(CR 6 R 7 )2O-、-CR 6 R 7 -O(CR 6 R 7 )3O-、-(CR 6 R 7 )C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )N(R 5 )C(O)-(CR 6 R 7 )2-、-O(CR 6 R 7 )2N(R 5 )C(O)-(CR 6 R 7 )O-、-N(R 5 )-C(O)(CR 6 R 7 )2O(CR 6 R 7 )2-、-CR 6 R 7 O(CR 6 R 7 )2O-(CR 6 R 7 )2、-O(CR 6 R 7)2O(CR 6 R 7 )2-、-O(CR 6 R 7 )2O(CR 6 R 7 )2O-、-CR 6 R 7 O-CR 6 R 7 -C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )3O(CR 6 R 7 )2-、-(CR 6 R 7 )2O(CR 6 R 7 )3-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )4O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3-、-O(CR 6 R 7 )2O(CR 6 R 7 )3-、-(CR 6 R 7 )2-N(R 5 )-(CR 6 R7 ) 3-, -O(CR 6 R 7 ) 2-N(R 5 )-CR 6 R 7 -,-(CR 6 R 7 ) 2-N(R 5 )-(CR 6 R 7 ) 2-,-O-(CR 6 R 7 ) 2-,-O-(CR 6 R 7 ) 3-,-O-(CR 6 R 7 ) 4-,-O-(CR 6 R 7 ) 5-,-O-(CR 6 R 7 ) 2O-,-O-(CR 6 R 7 ) 3O-,-O-(CR 6 R 7 ) 4O- or -O-(CR 6 R 7 ) 5O-.

[0630] In some embodiments, -(L) p - is -CR 6 R 7 -O(CR 6 R 7 ) 2O-,-CR 6 R 7 -O(CR 6 R 7 ) 3O-,-(CR 6 R 7 )C(O)N(R 5 )-(CR 6 R 7 ) 2-,-(CR<0​​​​​​​​​​​​​​​​​​​​​​​​6 R 7 )2-、-CR 6 R 7 O(CR 6 R 7 )2O-(CR 6 R 7 )2、-O(CR 6 R 7 )2O(CR 6 R 7 )2-、-O(CR 6 R 7 )2O(CR 6 R 7 )2O-、-CR 6 R 7 O-CR 6 R 7 -C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )3O(CR 6 R 7 )2-、-(CR 6 R 7 )2O(CR 6 R 7 )3-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )4O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR6 R 7 )3-, -O(CR 6 R 7 )2O(CR 6 R 7 )3-, -(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )3-, -O(CR 6 R 7 )2-N(R 5 )-CR 6 R 7 -, -(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )2-, -O-(CR 6 R 7 )2-, -O-(CR 6 R 7 )3-, -O-(CR 6 R 7 )4-, -O-(CR 6 R 7 )5-, -O-(CR 6 R 7 )2O-, -O-(CR 6 R 7 )3O-, -O-(CR 6 R 7 )4O- or -O-(CR 6 R 7 )5O-.

[0631] In some embodiments, -(L) p - comprises -CR 6 R 7 -O(CR 6 R 7 )2O-, -CR 6 R 7 -O(CR 6 R 7 )3O-, -(CR 6 R 7 )C(O)N(R 5 )-(CR 6 R 7 )2-, -(CR 6 R 7 )N(R 5 )C(O)-(CR 6 R7 )2-、-O(CR 6 R 7 )2N(R 5 )C(O)-(CR 6 R 7 )O-、-N(R 5 )-C(O)(CR 6 R 7 )2O(CR 6 R 7 )2-、-CR 6 R 7 O(CR 6 R 7 )2O-(CR 6 R 7 )2、-O(CR 6 R 7 )2O(CR 6 R 7 )2O-、-CR 6 R 7 O-CR 6 R 7 -C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )3O(CR 6 R 7 )2-、-(CR 6 R 7 )2O(CR 6 R 7 )3-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )4O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2-、-CR 6 R 7 -N(R 5)-(CR 6 R 7 )3O-, -CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3-, -O(CR 6 R 7 )2O-CR 6 R 7 -, -O(CR 6 R 7 )2O(CR 6 R 7 )2-, -O(CR 6 R 7 )2O(CR 6 R 7 )3-, -(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )3-, -O(CR 6 R 7 )2-N(R 5 )-CR 6 R 7 -, -(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )2-, -O-(CR 6 R 7 )2-, -O-(CR 6 R 7 )3-, -O-(CR 6 R 7 )4-, -O-(CR 6 R 7 )5-, -O-(CR 6 R 7 )2O-, -O-(CR 6 R 7 )3O-, -O-(CR 6 R 7 )4O- or -O-(CR 6 R 7 )5O-.

[0632] In some embodiments, -(L) p - is -CR 6 R 7 -O(CR 6 R 7)2O-、-CR 6 R 7 -O(CR 6 R 7 )3O-、-(CR 6 R 7 )C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )N(R 5 )C(O)-(CR 6 R 7 )2-、-O(CR 6 R 7 )2N(R 5 )C(O)-(CR 6 R 7 )O-、-N(R 5 )-C(O)(CR 6 R 7 )2O(CR 6 R 7 )2-、-CR 6 R 7 O(CR 6 R 7 )2O-(CR 6 R 7 )2、-O(CR 6 R 7 )2O(CR 6 R 7 )2O-、-CR 6 R 7 O-CR 6 R 7 -C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )3O(CR 6 R 7 )2-、-(CR 6 R 7 )2O(CR 6 R 7 )3-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )4O-、-CR 6 R 7 -N(R 5 )-(CR 6 R7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3-、-O(CR 6 R 7 )2O-CR 6 R 7 -、-O(CR 6 R 7 )2O(CR 6 R 7 )2-、-O(CR 6 R 7 )2O(CR 6 R 7 )3-、-(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )3-、-O(CR 6 R 7 )2-N(R 5 )-CR 6 R 7 -、-(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )2-、-O-(CR 6 R 7 )2-、-O-(CR 6 R 7 )3-、-O-(CR 6 R 7 )4-、-O-(CR 6 R 7 )5-、-O-(CR 6 R 7)2O-、-O-(CR 6 R 7 )3O-、-O-(CR 6 R 7 )4O-or-O-(CR 6 R 7 )5O-.

[0633] In some embodiments, each R 5 is H, methyl, ethyl, -C(O)CH3 or -C(O)CH2CH3; or R 5 With R 6 In some embodiments, each R 6 is H or C1-C6 alkyl; or R 6 With R 5 In some embodiments, one R 6 is methyl and the rest R 6 and R 7 For H.

[0634] In some embodiments, each R 5 are independently H, methyl, ethyl, -C(O)CH3 or -C(O)CH2CH3; or R 5 If it exists, and R 6 or R 7 If present, together with the one or more atoms to which it is attached, they form a 3- to 7-membered heterocycloalkyl group; wherein when R 5 and R 6 or R 7 Each hydrogen atom in the 3- to 7-membered heterocycloalkyl group formed when joined together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NRe C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0635] In some embodiments, R 6 and R 7 If present, together with the one or more atoms to which it is attached, they form a 3- to 7-membered heterocycloalkyl group; wherein when R 6 and R 7 Each hydrogen atom in the 3- to 7-membered heterocycloalkyl group formed when joined together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

[0636] In some embodiments, -(L) p- Containing -O-(CH2)2O-CH2-, -OC(H)(CH3)-CH2-O-CH2-, -CH2O-(CH2)2O-, -C(H)(CH3)-O-(CH2)2O-, -CH2N(H)-(CH2)2O-, -CH2N(CH3)-(CH2)2O-, -CH2N(CH2CH3)-(CH2)2O-, -O(CH2)2N(H)CH2-, -O(CH2)2N(CH3)CH2-, -OCH2-C(H)(CH3)-N(CH(CH3)2)CH2-, -OCH2-C(H)(CH2F)-N(CH3)CH2-, -OCH2-C(H)(CH2CH3)-N(CH3)CH2-, -O(CH2)2N(C(O)CH3)CH2-, -OC(H)(CH3)CH2N(H)CH2-, -OC(H)(CH3)CH2N(CH3)CH2-, -OC(H)(CH2CN)CH2N(CH3)CH2-, -OC(H)(CH2CH3)CH2N(CH3)CH2-, -OC(H)(CH2F)CH2N(CH3)CH2-, -OC(H)(CHF2)CH2N(CH3)CH2-, -OC(H)(CH2OH)CH2N(CH3)CH2-, -OC(H)(CH3)C(O)N(CH3)CH2-, -OC(H)(cyclobutyl)CH2N(CH3)CH2-, -OC(H)(CH3)CH2N(CH2CH3)CH2-, -OC(H)(CH3)CH2N(CH(CH3)2)-CH2-, -OC(H)(CH3)CH2N(CH3)-C(H)(CH3)-, -OC(H)(CH3)CH2N(CH(oxetan-3-yl)-CH2-, -OC(H)(CH3)CH2N(cyclopropyl)-CH2-, -OCH2C(H)(CH3)N(cyclopropyl)-CH2-, -OC(H)(CH3)CH2N(C(O)CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH2CH3)CH2-, -CH2N(H)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-C(H)(CH3)-CH2O-, -CH2N(CH3)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-(CH2)-(C(H)CH3)O-, -O(CH2)2-, -O(CH2)3-, -O(CH2)4-, -O(CH2)3O-, -O(CH2)4O-, -O(CH2)5O-, -O-(C(H)(CH3)-(CH2)2O-, -O(CH2)2-C(H)(CH3)-O--O(CH2)2C(H)(CH3)CH2O-, -O(CH2)3C(H)(CH3)CH2O-, -O(CH2)2N(H)C(O)-(CH2)O-, -O(CH2)2N(CH3)C(O)-(C H2)O-, -O(CH2)2O(CH2)2O-, -OC(H)(CH3)CH2OCH2-, -O(CH2)2OCH2C(H)(CH3)O-, -O(CH2)2OC(H)(CH3)-CH2O-,

[0637] In some embodiments, -(L) p- is -O-(CH2)2O-CH2-, -OC(H)(CH3)-CH2-O-CH2-, -CH2O-(CH2)2O-, -C(H)(CH3)-O-(CH2)2O-, -CH2N(H)-(CH2)2O-, -CH2N(CH3)-(CH2)2O-, -CH2N(CH2CH3)-(CH2)2O-, -O(CH2)2N(H)CH2-, -O(CH2)2N(CH3)CH2-, -OCH2-C(H)(CH3)-N(CH(CH3)2)CH2-, -OCH2-C(H)(CH2F)-N(CH3)CH2-, -OCH2-C(H)(CH2CH3)-N(CH3)CH2-, -O(CH2)2N(C(O)CH3)CH2-, -OC(H)(CH3)CH2N(H)CH2-, -OC(H)(CH3)CH2N(CH3)CH2-, -OC(H)(CH2CN)CH2N(CH3)CH2-, -OC(H)(CH2CH3)CH2N(CH3)CH2-, -OC(H)(CH2F)CH2N(CH3)CH2-, -OC(H)(CHF(2))CH2N(CH3)CH2-, -OC(H)(CH2OH)CH2N(CH3)CH2-, -OC(H)(CH3)C(O)N(CH3)CH2-, -OC(H)(cyclobutyl)CH2N(CH3)CH2-, -OC(H)(CH3)CH2N(CH(CH3)2)-CH2-, -OC(H)(CH3)CH2N(CH3)-C(H)(CH3)-, OC(H)(CH3)CH2N(oxetan-3-yl)-CH2-, -OC(H)(CH3)CH2N(cyclopropyl)-CH2-, -OCH2C(H)(CH3)N(cyclopropyl)-CH2-, -OC(H)(CH3)CH2N(C(O)CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH2CH3)CH2-, -CH2N(H)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-C(H)(CH3)-CH2O-, -CH2N(CH3)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-(CH2)-(C(H)CH3)O-, -O(CH2)2-, -O(CH2)3-, -O(CH2)4-, -O(CH2)3O-, -O(CH2)4O-, -O(CH2)5O-, -O-(C(H)(CH3)-(CH2)2O-, -O(CH2)2-C(H)(CH3)-O--O(CH2)2C(H)(CH3)CH2O-, -O(CH2)3C(H)(CH3)CH2O-, -O(CH2)2N(H)C(O)-(CH2)O-, -O(CH2)2N(CH3)C(O)-(CH2)O-, -O(CH2)2O(CH2)2O-, -OC(H)(CH3)CH2OCH2-, -O(CH2)2OCH2C(H)(CH3)O-, -O(CH2)2OC(H)(CH3)-CH2O-

[0638] In some embodiments, -(L) p - includes -CH2O-(CH2)2O-, -C(H)(CH3)-O-(CH2)2O-, -CH2N(H)-(CH2)2O-, -CH2N(CH3)-(CH2)2O-, -CH2N(CH2CH3)-(CH2)2O-, -O(CH2)2N(H)CH2-, -O(CH2)2N(CH3)CH2-, -O(CH2)2N(C(O)CH3)CH2-, -O(C(H)(CH3))CH2N(H)CH2-, -O(C(H)(CH3))CH2N(CH3)CH2-, -O(C(H)(CH3))CH2N(CH2CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH2CH3)CH2-, -CH2N(H)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-(CH2)2(C(H)CH3)CH2O-, -O(CH2)2-, -O(CH2)3-, -O(CH2)4-, -O(CH2)3O-, -O(CH2)4O-, -O(CH2)5O-, -O-(C(H)(CH3)-(CH2)2O-, -O(CH2)2-(C(H)(CH3)-O-, -O(CH2)3C(H)(CH3)CH2O-, -O(CH2)2N(H)C(O)-(CH2)O-, -O(CH2)2N(CH3)C(O)-(CH2)O-, -O(CH2)2O(CH2)2O-, -O(CH2)2OCH2C(H)(CH3)O-, -O(CH2)2OC(H)(CH3)-CH2O- or

[0639] In some embodiments, -(L) p- is -CH2O-(CH2)2O-, -C(H)(CH3)-O-(CH2)2O-, -CH2N(H)-(CH2)2O-, -CH2N(CH3)-(CH2)2O-, -CH2N(CH2CH3)-(CH2)2O-, -O(CH2)2N(H)CH2-, -O(CH2)2N(CH3)CH2-, -O(CH2)2N(C(O)CH3) CH2-, -O(C(H)(CH3))CH2N(H)CH2-, -O(C(H)(CH3))CH2N(CH3)CH2-, -O(C(H)(CH3))CH2N(CH 2CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH2CH3)CH2-, -CH 2N(H)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-(CH2)2(C(H)CH3)CH2O-, -O(CH2)2-, -O(CH2)3 -, -O(CH2)4-, -O(CH2)3O-, -O(CH2)4O-, -O(CH2)5O-, -O-(C(H)(CH3)-(CH2)2O-, -O(CH2)2-( C(H)(CH3)-O-, -O(CH2)3C(H)(CH3)CH2O-, -O(CH2)2N(H)C(O)-(CH2)O-, -O(CH2)2N(CH3)C( O)-(CH2)O-, -O(CH2)2O(CH2)2O-, -O(CH2)2OCH2C(H)(CH3)O-, -O(CH2)2OC(H)(CH3)-CH2O- and

[0640] In combination with any of the embodiments described herein, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-. With respect to any embodiment described herein, (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment. With respect to any of the embodiments described herein, (L) p Does not contain a -NR directly covalently linked to ring A 5 C(O)-, and (L) p Does not contain an -O-CR directly covalently attached to ring A 6 R 7 - fragment.

[0641] In some embodiments, the present disclosure provides a compound selected from the group consisting of: (11E)-1-methyl-1,18,19,21-tetrahydro-8H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-f][1,4,12,13]benzodioxadiazacyclooctadecane;

[0642] (11E)-1-[(methylsulfonyl)methyl]-19,20-dihydro-1H,8H,18H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-f][1,5,12,13]benzodioxadiazacyclooctadecane;

[0643] (11E)-1-Methyl-18,19,20,21-tetrahydro-1H,8H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-g][1,6,13,14]benzodioxadiazacyclononadecanone;

[0644] (10R,16E)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0645] (10R,16E)-3-methyl-13-[(4-methylpiperazin-1-yl)methyl]-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0646] (10R,16E)-13-[(dimethylamino)methyl]-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0647] (10R,16E)-3-methyl-13-(1-methylpiperidin-4-yl)-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0648] (10R,16E)-13-(2-methoxypropan-2-yl)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0649] (10R,16E)-3-methyl-13-(4-methylpiperazin-1-yl)-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0650] (10R,16E)-14-fluoro-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0651] (10R,16E)-14-(2-hydroxypropan-2-yl)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-25-one;

[0652] (10R,16E)-14-{(2S)-2-[(methylsulfonyl)methyl]azetidin-1-yl}-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepin-25-one;

[0653] (10R,16E)-3-methyl-25-oxo-3,5,6,9,10,19-hexahydro-8H-20,22-etheno-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecan-14-carbonitrile; and

[0654] (10R,16E)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazepine octadecane;

[0655] or a pharmaceutically acceptable salt thereof.

[0656] 32. The compound of clause 1 or 2, which is selected from the group consisting of: (18E)-8-methyl-N-(propan-2-yl)-8,9,11,12-tetrahydro-2H-3,5-ethene-bridged bispyrazolo[3′,4′:9,10;4″,3″:13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0657] (18E)-N,8-dimethyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0658] (18E)-N,N,8-trimethyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0659] (18E)-N-ethyl-8-methyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadecafluoro[5,6-b]pyridine-16-carboxamide;

[0660] (10S,18E)-8,10,16-trimethyl-2,8,11,12-tetrahydro-10H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,5]dioxacyclopentadecafluoro[7,6-b]pyridine;

[0661] (10S,18E)-17-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-ethylenedipyrazolo[3,4-j:4',3'-n]pyrido[4,3-f][1,4]oxazacyclopentadecane; and

[0662] (10S,18E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-ethylene-bridged bipyrazolo[3,4-j:4',3'-n]pyrido[3,2-f][1,4]oxazaheterocyclopentadecane;

[0663] or a pharmaceutically acceptable salt thereof.

[0664] 33. The compound of clause 1 or 2, which is selected from the group consisting of: (17E)-8,14,16-trimethyl-2,8,9,11,12,14-hexahydro-3,5-etheno[1,4]dioxopentadecano[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0665] 2-[(17E)-8,9,16-trimethyl-8,9,11,12-tetrahydro-3,5-vinyl-bridged [1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazol-14(2H)-yl]ethan-1-ol;

[0666] (17E)-8,14,16-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0667] (17E)-19-Fluoro-8,14,16-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0668] (17E)-16-Ethyl-8,14-dimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0669] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-2-methylpropan-2-ol;

[0670] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]propan-2-one;

[0671] 2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethan-1-ol;

[0672] (17E)-8,16-Dimethyl-14-[2-(pyrrolidin-1-yl)ethyl]-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0673] (3S)-1-{2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethyl}pyrrolidin-3-ol;

[0674] (17E)-16-Ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0675] (10S,17E)-8,10,14,16-tetramethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0676] (10R,17E)-8,10,14,16-tetramethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0677] (12S,17E)-16-Ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0678] (12R,17E)-16-ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0679] (10S,17E)-16-Ethyl-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0680] (10S,17E)-16-cyclopropyl-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0681] (17E)-16-(methoxymethyl)-8,14-dimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0682] (17E)-8,14,16-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0683] 1-[(17E)-8,14,16-trimethyl-2,8,10,11,13,14-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0684] (17E)-8,12,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0685] (17E)-6,8,12,14,16-pentamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethylenetriazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0686] (17E)-16-Ethyl-8,12,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0687] (17E)-7,14,16-trimethyl-2,10,11,12,13,14-hexahydro-7H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0688] (17E)-7,12,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-7H-3,5-ethylenetriazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0689] 2-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0690] (17E)-8,14,16-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0691] (17E)-8,10,14,16-tetramethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0692] 2-[(17E)-8,16-dimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0693] 2-[(17E)-8,10,16-trimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0694] 2-[(17E)-10-ethyl-8,16-dimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0695] (19E)-8,13,16,18-Tetramethyl-2,11,12,13,14,16-hexahydro-8H,10H-3,5-ethenyl[1,7]dioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0696] 2-[(19E)-8,13,18-Trimethyl-2,8,11,12,13,14-hexahydro-10H,16H-3,5-vinyl-bridged [1,7]dioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazol-16-yl]ethan-1-ol;

[0697] (19E)-8,16,18-trimethyl-2,11,12,16-tetrahydro-8H,10H-3,5-ethene-bridged tripyrazolo[3,4-h:3',4'-l:4",3"-p][1,7,4]dioxazacycloheptadecan-13(14H)-one;

[0698] (19E)-8,12,16,18-tetramethyl-2,11,12,16-tetrahydro-8H,10H-3,5-ethylenetriazolo[3,4-h:3',4'-l:4",3"-p][1,7,4]dioxazacycloheptadecan-13(14H)-one;

[0699] (13R,19E)-8,13,16,18-tetramethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0700] (13S,19E)-8,13,16,18-tetramethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxetane heptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0701] 2-[(19E)-8,13,18-trimethyl-2,8,10,11,13,14-hexahydro-16H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazol-16-yl]ethan-1-ol;

[0702] (19E)-8,13,18-Trimethyl-16-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0703] (3S)-1-{2-[(17E)-16-ethyl-8-methyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethyl}pyrrolidin-3-ol;

[0704] (19E)-22-Fluoro-8,16,18-trimethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole;

[0705] 3-[(17E)-16-Ethyl-8-methyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-N,N-dimethylpropan-1-amine;

[0706] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]pyrrolidin-3-ol;

[0707] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-1-methylpyrrolidin-3-ol;

[0708] (3R,4S)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]oxolan-3-ol;

[0709] (3S,4R)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]oxolan-3-ol;

[0710] (rac)-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutan-1-ol;

[0711] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]piperidin-3-ol;

[0712] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-1-methylpiperidin-3-ol;

[0713] (rac)-1,5-anhydro-2,3-dideoxy-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-L-threopentitol;

[0714] (rac)-1,5-anhydro-2,4-dideoxy-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-L-threopentitol;

[0715] (12R,17E)-8,10,12,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0716] (12S,17E)-8,10,12,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0717] (rac)-(3S,4S)-1-methyl-4-[(17E)-8,10,16-trimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]pyrrolidin-3-ol;

[0718] (11S,17E)-8,11,14,16-tetramethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0719] (17E)-8,9,16-Trimethyl-14-[2-(pyrrolidin-1-yl)ethyl]-2,8,9,11,12,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0720] [(10S,17E)-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-16-yl]methanol;

[0721] N 1 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutyl}-N 1 ,N 2 ,N 2 -Trimethylethylene-1,2-diamine;

[0722] (11S,17E)-8,10,11,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0723] N 2 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutyl}-N 1 ,N1 -dimethylethylene-1,2-diamine;

[0724] (10R,15E)-3,12,14-trimethyl-5,6,9,10,12,18-hexahydro-3H,8H-19,21-ethenyl-7,10-methantripyrazolo[3,4-i:3',4'-m:4",3"-q][1,8,4]dioxazacyclooctadecan-24-one;

[0725] (17E)-16-Ethyl-8,10,14-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0726] (17E)-10-ethyl-8,14,16-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0727] 2-[(10S,17E)-8,10,16-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0728] 2-[(10S,17E)-19-fluoro-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0729] (17E)-8,10,16-trimethyl-14-(1-methylpyrrolidin-3-yl)-2,9,10,11,12,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0730] 2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0731] (10S,17E)-8,10,12,14,16-pentamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0732] (10R,19E)-8,16,18-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0733] (2S)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-2-ol;

[0734] 2-[(10S,17E)-19-chloro-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0735] (2R)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-2-ol;

[0736] 2-[(10S,17E)-16-ethyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0737] 2-[(10S,17E)-12-ethyl-8,10,16-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0738] (10S,17E)-8,10,12,14-tetramethyl-16-[(piperidin-4-yl)oxy]-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0739] 2-[(10R,19E)-18-Ethoxy-8-methyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0740] 2-[(10S,17E)-6,8,10,12,16-pentamethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0741] (10S,17E)-8,10,14,16-tetramethyl-12-(oxetan-3-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0742] 2-[(10S,17E)-16-ethoxy-6,8,10-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0743] (10S,17E)-16-{[1-(methylsulfonyl)piperidin-4-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0744] (10S,13R,17E)-8,10,12,13,14,16-hexamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0745] (10S,13S,17E)-8,10,12,13,14,16-hexamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0746] 2-{(10S,17E)-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0747] (10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0748] (10S,17E)-16-[(azetidin-3-yl)oxy]-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0749] (10S,17E)-16-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0750] 2-[(10S,17E)-16-ethoxy-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0751] 2-[(17E)-10-cyclobutyl-8,12,16-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0752] (10S,17E)-8,10,12,14-tetramethyl-16-{[(3S)-pyrrolidin-3-yl]oxy}-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0753] (10S,17E)-16-{[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0754] (2S)-2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0755] (10S,17E)-16-ethoxy-8,10,14-trimethyl-12-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0756] (10S,17E)-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[0757] (10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-16-carbonitrile;

[0758] (10R,19E)-18-Ethoxy-8,16-dimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0759] (10S,17E)-12-cyclopropyl-8,10,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0760] (10S,17E)-8,10,12,14-tetramethyl-16-(2,2,2-trifluoroethoxy)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0761] {[(10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile;

[0762] (10S,17E)-10,14,16-trimethyl-8-[(methylthio)methyl]-12-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0763] (10S,17E)-12-Ethyl-8,10,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0764] 2-[(10S,17E)-16-ethoxy-8-ethyl-10,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0765] 2-{(10S,17E)-8-ethyl-10,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0766] (2R)-2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0767] 2-[(10S,17E)-16-ethoxy-19-fluoro-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0768] 2-[(10S,17E)-16-{[1-(methylsulfonyl)piperidin-4-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0769] (10S,19E)-8,16,18-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0770] 2-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0771] 2-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0772] 2-{(10S,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0773] 2-[(10S,17E)-16-{[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0774] 2-[(10S,17E)-16-bromo-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0775] 2-{(10S,17E)-16-[(azetidin-3-yl)oxy]-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0776] (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0777] (10S,17E)-16-{[3-(methylsulfonyl)cyclobutyl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0778] (10S,19E)-18-Ethoxy-8,16-dimethyl-2,8,11,12,15,16-hexahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane-13(10H)-one;

[0779] (10R,19E)-18-Ethoxy-8,16-dimethyl-2,8,11,12,15,16-hexahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane-13(10H)-one;

[0780] 2-[(10R,19E)-18-Ethoxy-22-fluoro-8-methyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0781] 2-{(11S,17E)-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0782] 2-{(10R,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0783] 2-{(11S,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0784] 2-{(10R,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0785] 2-[(10R,17E)-12-cyclopropyl-16-ethoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0786] 2-[(10R,17E)-16-ethoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0787] 2-[(11S,17E)-12-cyclopropyl-16-ethoxy-8,11-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0788] 2-[(10R,19E)-22-fluoro-8-methyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0789] (2S)-2-{(10S,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0790] 2-{(11S,17E)-6,8,11-trimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0791] 2-{(10R,17E)-6,8,10-trimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0792] {[(10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile;

[0793] 2-[(10R,17E)-12-cyclopropyl-16-ethoxy-6,8,10-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0794] 2-[(11S,17E)-12-cyclopropyl-16-ethoxy-6,8,11-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0795] (10S,17E)-16-Ethoxy-12-ethyl-19-fluoro-8,10,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0796] (2S)-2-{(10R,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0797] (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-16-carbonitrile;

[0798] (10S,17E)-12-Ethyl-8,10,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0799] (10S,17E)-19-Fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0800] 2-[(10S,17E)-19-fluoro-8,10,12-trimethyl-16-(2,2,2-trifluoroethoxy)-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0801] 2-{(10R,17E)-12-cyclopropyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0802] 2-{(11S,17E)-12-cyclopropyl-8,11-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0803] (2S)-2-[(10S,17E)-16-ethoxy-19-fluoro-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0804] (2S)-2-[(10S,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0805] 2-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0806] 1-[(10R,17E)-16-ethoxy-14-(2-hydroxyethyl)-8,10-dimethyl-2,8,10,11,13,14-hexahydro-12H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0807] Ethyl [(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]acetate;

[0808] (2S)-2-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0809] (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,12,13,14-tetrahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-11(10H)-one;

[0810] 2-[(10S,17E)-16-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0811] 1-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]-2-methylpropan-2-ol;

[0812] 2-{(10S,13R,17E)-8,10,12,13-tetramethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0813] 2-{(10S,13S,17E)-8,10,12,13-tetramethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0814] 2-{(17E)-10-(Fluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0815] 2-{(17E)-11-(Fluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0816] (2S)-1-{(10R,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol;

[0817] (2S)-2-[(11S,17E)-16-Ethoxy-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0818] (2S)-2-[(10R,17E)-16-ethoxy-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0819] (2S)-2-{(11S,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0820] (2S)-2-{(10R,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol;

[0821] 2-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}acetamide;

[0822] (10S,17E)-19-Fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol;

[0823] 2-[(8aR,19E)-1-(cyclopropylmethoxy)-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0824] (10R,18E)-17-Ethoxy-8,15-dimethyl-2,8,11,12,14,15-hexahydro-10H-3,5-etheno-10,13-methanotripyrazolo[3,4-g:3',4'-k:4",3"-o][1,5]oxazacyclohexadecanone;

[0825] {(17E)-14-(2-hydroxyethyl)-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,10,11,12,13,14-hexahydro-7H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-7-yl}acetonitrile;

[0826] (17E)-16-Ethoxy-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno-10,12-methanotripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0827] 2-[(10S,17E)-16-Ethoxy-19-fluoro-6,8,10-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0828] 2-[(8aR,9R,19E)-1-ethoxy-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0829] 2-[(8aR,9S,19E)-1-ethoxy-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0830] 2-[(19E)-18-Ethoxy-8,21-dimethyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0831] 2-[(8aR,9R,19E)-1-ethoxy-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0832] 2-[(8aR,9S,19E)-1-ethoxy-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0833] 2-[(19E)-18-Ethoxy-22-fluoro-8,21-dimethyl-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0834] 2-{(10S,17E)-8-cyclopropyl-10,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0835] (10S,13S,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0836] (10R,13R,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0837] (10R,13S,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0838] (10S,13R,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazaheptadecane;

[0839] 2-{(10R,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0840] 2-[(8aR,9S,19E)-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0841] 2-[(8aR,9R,19E)-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0842] 2-[(19E)-8,21-Dimethyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0843] 2-[(8aR,9R,19E)-22-fluoro-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0844] 2-[(8aR,9S,19E)-22-fluoro-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol;

[0845] 2-[(19E)-22-Fluoro-8,21-dimethyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methantripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol;

[0846] 2-{(10R,17E)-10-(hydroxymethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0847] 2-[(11S,17E)-16-ethoxy-11-ethyl-8,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0848] 2-[(10S,17E)-16-ethoxy-10-ethyl-8,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0849] 2-[(10S,17E)-16-(methoxymethyl)-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0850] 1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}-2-methylpropan-2-ol;

[0851] 1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-one;

[0852] (10R,17E)-14-(2-hydroxyethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-10-carbonitrile;

[0853] 2-{(10S,17E)-8,10,12-trimethyl-16-[(methylamino)methyl]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0854] 2-{(10S,17E)-16-[(dimethylamino)methyl]-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0855] (2R)-2-{[(10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}propionitrile;

[0856] (2S)-2-{[(10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}propionitrile;

[0857] 2-[(4aS,7aS,13E)-12-ethoxy-3,6,8-trimethyl-4a,5,6,7,7a,8,9,16-octahydro-17,19-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecan-10(3H)-yl]ethan-1-ol;

[0858] 2-[(4aR,7aR,13E)-12-ethoxy-3,6,8-trimethyl-4a,5,6,7,7a,8,9,16-octahydro-17,19-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecan-10(3H)-yl]ethan-1-ol;

[0859] {[(8aR,19E)-3-(2-hydroxyethyl)-9,11-dimethyl-3,4,7,8,8a,9,11,17-octahydro-6H-14,16-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-1-yl]oxy}acetonitrile;

[0860] {[(8aR,9R,19E)-3-(2-hydroxyethyl)-9,11-dimethyl-3,4,7,8,8a,9,11,17-octahydro-6H-14,16-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-1-yl]oxy}acetonitrile;

[0861] 2-{(10S,17E)-10-(difluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0862] 2-{(10R,17E)-10-(difluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0863] 2-{(10S,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0864] 2-[(10R,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0865] (4aS,7aS,13E)-12-ethoxy-3,8,10-trimethyl-3,4a,5,6,7,7a,8,9,10,16-decahydro-17,19-ethylene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecane;

[0866] (4aR,7aR,13E)-12-ethoxy-3,8,10-trimethyl-3,4a,5,6,7,7a,8,9,10,16-decahydro-17,19-ethylene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecane;

[0867] (2S)-1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol;

[0868] 2-{(11R,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0869] 2-{(10S,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol;

[0870] 2-[(11R,17E)-16-ethoxy-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0871] 2-[(10S,17E)-16-ethoxy-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0872] {[(10S,17E)-19-Fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile;

[0873] 2-[(10R,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0874] (2S)-2-[(10R,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0875] 2-[(10S,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0876] (2S)-2-[(10R,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0877] (10S,17E)-16-Ethoxy-12-ethyl-14-(2-hydroxyethyl)-8,10-dimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-6-carbonitrile;

[0878] 2-[(10S,17E)-16-ethoxy-6-ethynyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0879] 2-[(10S,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0880] 2-[(10S,17E)-16-(ethylamino)-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0881] (2S)-1-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol;

[0882] 2-[(10S,17E)-6-amino-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol;

[0883] (2S)-2-[(10S,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol;

[0884] 2,2'-[(10S,17E)-10,12-dimethyl-16-[(propan-2-yl)oxy]-10,11,12,13-tetrahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-8,14(2H)-diyl]di(ethan-1-ol);

[0885] (17E)-16-Ethyl-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0886] 2-[(17E)-8,16-dimethyl-2,10,11,13-tetrahydro-3,5-vinyl-bridged [1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14(8H)-yl]-N-ethylacetamide;

[0887] (17E)-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[0888] (17E)-8,14,16-trimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0889] (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0890] (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[0891] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[6,5-d][1,2]oxazole-16-carbonitrile;

[0892] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[6,5-d][1,2]thiazole-16-carbonitrile;

[0893] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecafluoro[5,6-c][1,2]oxazole-16-carbonitrile;

[0894] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecafluoro[5,6-c][1,2]thiazole-16-carbonitrile; and

[0895] (10S,17E)-16-Ethyl-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0896] or a pharmaceutically acceptable salt thereof.

[0897] 34. The compound of clause 1 or 2, which is selected from the group consisting of: (17E)-8,15,16-trimethyl-2,8,9,11,12,15-hexahydro-3,5-etheno[1,4]dioxopentadecano[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0898] (17E)-8,15,16-trimethyl-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0899] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]propan-2-one;

[0900] 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl-bridged[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-2-methylpropan-2-ol;

[0901] 2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]ethan-1-ol;

[0902] (17E)-8,16-Dimethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0903] (10S,17E)-8,10,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0904] (17E)-8,15,16-trimethyl-2,10,11,12,13,15-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0905] 1-[(17E)-8,15,16-trimethyl-2,8,10,11,13,15-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0906] (17E)-8,12,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0907] 1-[(10S,17E)-8,10,15,16-tetramethyl-2,8,10,11,13,15-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one;

[0908] (10S,17E)-8,10,12,15,16-pentamethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0909] 2-[(10S,17E)-8,10,16-trimethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]ethan-1-ol;

[0910] 2-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]ethan-1-ol;

[0911] (10S,17E)-12-Ethyl-8,10,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0912] 1-[(10S,17E)-8,10,15,16-tetramethyl-2,8,10,11,13,15-hexahydro-12H-3,5-vinyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]propan-1-one;

[0913] 2-[(19E)-8,13,18-Trimethyl-2,8,11,12,13,14-hexahydro-10H,17H-3,5-vinyl[1,7]dioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazol-17-yl]ethan-1-ol;

[0914] (13E)-3-methyl-3,5,6,7,8,16-hexahydro-9,12-(azepanyl)-17,19-ethylene-bridged bipyrazolo[3,4-1:4',3'-p][1,6]oxazaheterocycloheptadecanone;

[0915] (18E)-8-Methyl-2,8,10,11,12,13-hexahydro-3,5-ethylenetripyrazolo[1,5-f:3',4'-j:4",3"-n][1,6]oxazacyclopentadecane;

[0916] (17E)-15-(2-methoxyethyl)-8,16-dimethyl-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[0917] 2-[(17E)-8,9,16-trimethyl-8,9,11,12-tetrahydro-3,5-vinyl-bridged [1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazol-15(2H)-yl]ethan-1-ol;

[0918] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]piperidin-3-ol;

[0919] (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-1-methylpiperidin-3-ol;

[0920] (17E)-8,9,16-Trimethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,8,9,11,12,15-hexahydro-3,5-etheno[1,4]dioxacyclopentadecafluoro[11,10-c:15,14-c':6,7-c"]tripyrazole;

[0921] (rac)-1,5-anhydro-2,3-dideoxy-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxopentadecano[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-L-threopentitol;

[0922] 1,5-Anhydro-2,4-dideoxy-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-L-threopentitol;

[0923] (10S,17E)-8,10,12,16-tetramethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0924] (10S,17E)-8,10,12,16-tetramethyl-15-[2-(4-methylpiperazin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0925] (20E)-8,18-dimethyl-2,8,11,12-tetrahydro-10H-3,5-ethylene-bridged bispyrazolo[3",4":10',11';4"',3"':14',15'][1,5]dioxacyclopentadecano[6',7':3,4]pyrazolo[1,5-a]pyrazin-19(18H)-one;

[0926] (10S,17E)-8,10,12,16-tetramethyl-15-[2-(morpholin-4-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0927] 4-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]butan-2-ol;

[0928] N 1 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]cyclobutyl}-N 1 ,N 2 ,N 2 -Trimethylethylene-1,2-diamine;

[0929] 2-Methyl-4-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]butan-2-ol;

[0930] 2-Methyl-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol;

[0931] N 2 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-vinyl[1,5]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]cyclobutyl}-N 1 ,N 1 -dimethylethylene-1,2-diamine;

[0932] (17E)-8,10,16-trimethyl-15-(1-methylpyrrolidin-3-yl)-2,9,10,11,12,15-hexahydro-8H-3,5-vinyltripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0933] (10R,17E)-8,10,12,16-tetramethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0934] (2S)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol;

[0935] (10S,17E)-8,10,12,14,15-pentamethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0936] (2R)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol;

[0937] (10S,17E)-8,10,12,14,16-pentamethyl-2,10,11,12,13,16-hexahydro-8H-3,5-ethylenetripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0938] (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[3,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0939] (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0940] (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-ethylene-bridged bipyrazolo[3,4-j:4',3'-n][1,2]thiazolo[3,4-f][1,4]oxazacyclopentadecane;

[0941] (10S,20E)-18-[2-(methylsulfonyl)ethyl]-8,10,12-trimethyl-2,8,10,11,12,13,16,17,18,19-decahydro-3,5-vinyl-bridged pyrazino[1',2':1,5]pyrazolo[3,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0942] (10S,17E)-16-cyclopropyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0943] (10S,17E)-16-Ethyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0944] (10S,17E)-8,10,12-trimethyl-16-(propan-2-yl)-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0945] (10S,17E)-8,10,12-trimethyl-16-(propan-2-yl)-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane;

[0946] (10S,17E)-16-Ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl-bridged [1,2] oxazolo [5,4-f] bipyrazolo [3,4-j: 4',3'-n][1,4] oxazacyclopentadecane;

[0947] (10R,17E)-8,10,14,15-tetramethyl-12-(propan-2-yl)-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0948] (10S,17E)-8,10,14,15-tetramethyl-12-(propan-2-yl)-2,10,11,12,13,15-hexahydro-8H-3,5-ethenyltripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane;

[0949] (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]oxazole;

[0950] (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]oxazole-16-carbonitrile;

[0951] (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole;

[0952] (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole-16-carbonitrile;

[0953] (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole;

[0954] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile;

[0955] (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]thiazole;

[0956] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile;

[0957] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]thiazole-16-carbonitrile;

[0958] (17E)-8,16-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole;

[0959] (17E)-8,16-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylenedipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecafluoro[7,6-d][1,2]oxazole; and

[0960] (17E)-8,16-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecafluoro[6,7-c][1,2]thiazole;

[0961] or a pharmaceutically acceptable salt thereof.

[0962] The following represent illustrative examples of compounds of formula (I)-(XII):

[0963]

[0964]

[0965]

[0966]

[0967]

[0968]

[0969]

[0970]

[0971]

[0972]

[0973]

[0974]

[0975]

[0976]

[0977]

[0978]

[0979]

[0980]

[0981]

[0982]

[0983]

[0984]

[0985]

[0986]

[0987]

[0988]

[0989]

[0990]

[0991]

[0992]

[0993]

[0994]

[0995]

[0996]

[0997]

[0998]

[0999]

[1000]

[1001]

[1002]

[1003]

[1004]

[1005]

[1006]

[1007]

[1008]

[1009]

[1010]

[1011]

[1012]

[1013]

[1014]

[1015]

[1016]

[1017]

[1018]

[1019]

[1020]

[1021]

[1022]

[1023]

[1024]

[1025]

[1026]

[1027]

[1028]

[1029]

[1030]

[1031]

[1032]

[1033]

[1034]

[1035]

[1036]

[1037]

[1038]

[1039]

[1040]

[1041]

[1042] and pharmaceutically acceptable salts thereof.

[1043] One skilled in the art will recognize that the materials listed or described herein are not exhaustive and that other materials within the scope of these defined terms may also be selected.

[1044] Alternative Embodiments

[1045] Certain compounds of the present disclosure are also described in the following alternative embodiments. Those skilled in the art will recognize that the alternative embodiments described herein are consistent with the embodiments described throughout the present disclosure. The alternative embodiments describe certain aspects of the present disclosure within the general teachings of the present disclosure and are described in a similar manner.

[1046] In some embodiments, the present disclosure provides a compound of Formula Ia or a pharmaceutically acceptable salt thereof,

[1047]

[1048] where R 1A 、R 2A 、R 3A 、R 4A 、R 5A 、R 6A 、R 7A 、R 8A 、A A 、B A 、m A 、n A 、p A and q A As described in this article.

[1049] In some embodiments, the present disclosure provides a compound of Formula IIA or a pharmaceutically acceptable salt thereof,

[1050]

[1051] where R 1A 、R 2A 、R 3A 、R 4A 、R 5A 、R 6A 、R 7A 、R 8A 、A A 、B A , Z A , Z 1A 、m A 、n A 、p A ,q A and As described in this article.

[1052] In some embodiments, the present disclosure provides a compound of formula IIIA or a pharmaceutically acceptable salt thereof,

[1053]

[1054] where R 3A 、R 4A 、R 5A 、R 6A 、R 7A 、R 8A 、A A 、B A 、X 1A 、X 2A 、X 3A , Z A , Z 1A 、Y 1A 、Y 2A、Y 3A 、p A ,q A and As described in this article.

[1055] In some embodiments, the present disclosure provides a compound of Formula IVA or a pharmaceutically acceptable salt thereof,

[1056]

[1057] where R 3A 、R 4A 、R 5A 、R 6A 、R 7A 、R 8A 、A A 、B A 、X 1A 、X 2A 、X 3A , Z A , Z 1A 、Y 1A 、Y 2A 、Y 3A and q A As described in this article.

[1058] In other aspects, the present disclosure relates to a pharmaceutical composition comprising at least one compound of Formula (IA)-(IVA) or a pharmaceutically acceptable salt thereof. The pharmaceutical composition according to the present disclosure may further comprise a pharmaceutically acceptable excipient.

[1059] In other aspects, the present disclosure relates to a compound of Formula (IA)-(IVA) or a pharmaceutically acceptable salt thereof, which is useful as a medicament.

[1060] In other aspects, the present disclosure relates to a method of treating a disease, such as cancer, comprising administering to a subject in need of such treatment an effective amount of at least one compound of Formula (IA)-(IVA) or a pharmaceutically acceptable salt thereof.

[1061] In other aspects, the present disclosure relates to the use of compounds of Formula (IA)-(IVA), or pharmaceutically acceptable salts thereof, in the preparation of a medicament for treating a disease, such as cancer, and the use of such compounds and salts for treating such diseases.

[1062] In other aspects, the present disclosure relates to a method of inhibiting ALK, comprising contacting a cell comprising one or more of ALK with an effective amount of at least one compound of Formula (IA)-(IVA) or a pharmaceutically acceptable salt thereof and / or with at least one pharmaceutical composition of the present disclosure, wherein the contacting is performed in vitro, ex vivo or in vivo.

[1063] Other embodiments, features and advantages of the present disclosure will be apparent from the following detailed description and from practicing the present disclosure. The compounds of the present disclosure may be described as embodiments in any of the following enumerated clauses. It should be understood that any embodiment described herein may be used in combination with any other embodiment described herein to the extent that the embodiments do not contradict each other.

[1064] 1. A compound of formula IA

[1065]

[1066] in

[1067] Ring A A and Ring B A are each independently a 5-membered heteroarylene group;

[1068] Each R 1A 、R 2A and R 8A If present, independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C6 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NRa S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)ORd 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2;

[1069] Each R 1A and R 5A or R 6A can be optionally combined with one or more atoms to which it is attached to form a C3-C6 cycloalkyl group, a 3-membered to a 7-membered heterocycloalkyl group, wherein when R 1A and R 5A or R 6A Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NRe R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2;

[1070] Each R 3A 、R 4A 、R 5A and R 6A are independently H, deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NRa R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10Each hydrogen atom in the aryl and 5- to 10-membered heteroaryl groups is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2; or R3A 、R 4A 、R 5A and R 6A The two of them, together with the carbon or carbon atoms to which they are attached, are optionally combined to form a C3-C6 cycloalkyl group, a 3-membered to 7-membered heterocycloalkyl group, wherein when R 3A 、R 4A 、R 5A and R 6A Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2;

[1071] R 7A are independently H, deuterium, -C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-S(O)2NR c R d 、-P(O)2R c R d 、-P(O)2NR c R d OR-P(O)2OR c ;

[1072] Each R a 、R b 、R c 、R d 、R e and R f independently selected from the group consisting of: H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10 aryl, 5- to 10-membered heteroaryl, and C1-C6 alkylene-5- to 10-membered heteroaryl, or R a and R b or R c and R d or R e and R f Together with the atoms to which they are attached, they form a 3- to 7-membered heterocycloalkyl group, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10Each hydrogen atom in an aryl, 5- to 10-membered heteroaryl, or C1-C6 alkylene-5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -OC1-C6 alkyl, -OC(O)-(H or C1-C6 alkyl), -OC(O)N(H or C1-C6 alkyl)2, -OC(O)N(C2-C6 alkylene), -OS(O)-(H or C1-C6 alkyl), -OS(O)2-(H or C1-C6 alkyl), -OS(O)N(H or C1-C6 alkyl)2, -OS(O)N(C2-C6 alkylene), -OS(O)2N(H or C1-C6 alkyl)2, -OS( C(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)O(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)N(H or C1-C6 alkyl) or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)C(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)2(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)2N(C2-C6 alkylene), -C(O)-(H or C1-C6 alkyl), -C(O)O (H or C1-C6 alkyl), -C(O)N(C2-C6 alkylene), -P(H or C1-C6 alkyl)2, -P(C2-C6 alkylene), -P(O)(H or C1-C6 alkyl)2, -P(O)(C2-C6 alkylene), -P(O)2(H or C1-C6 alkyl)2, -P(O)2(C2-C6 alkylene), -P(O)N(H or C1-C6 alkyl)2, -P(O)N(C2-C6 alkylene), -P(O)2N(H or C1-C6 alkyl)2, -P(O)2N(C2-C6 alkylene), -P(O)O(H or C1-C6 alkyl), -P(O)2O(H or C1-C6 alkyl), -CN or -NO2;

[1073] m A is 0, 1, 2, or 3;

[1074] n A is 0, 1, 2, or 3;

[1075] p A is 2, 3, or 4; and

[1076] q A is 0, 1, or 2;

[1077] or a pharmaceutically acceptable salt thereof.

[1078] 2. The compound of Example 1 or a pharmaceutically acceptable salt thereof, which has Formula IIA:

[1079]

[1080] in

[1081] Optionally a carbon-carbon single bond or a carbon-carbon double bond;

[1082] Z A for Where * is the covalent connection point with ether, ** is the covalent connection point with Z 1A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates that at the connection point** and The situation where one bond is a single bond and one bond is a double bond; Z 1A for Where *** is the covalent connection point with indazole, **** is the covalent connection point with Z A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates the connection point **** with A situation where one bond between the two is a single bond and one bond is a double bond; and ring B A It is a 5-membered heteroarylene group.

[1083] 3. The compound of embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, having formula IIIA:

[1084]

[1085] in

[1086] X 1A 、X 2A and X 3A are independently -O-, -S-, =C(H)-, =C(R1A )-、-N(H)-、-N(R 1A )- or =N-, and ring A A is a 5-membered heteroarylene group, provided that X 1A 、X 2A and X 3A At least one of them is not =C(H)- or =C(R 1A )-;

[1087] Y 1A 、Y 2A and Y 3A are independently -O-, -S-, =C(H)-, =C(R 2A )-、-N(H)-、-N(R 2A )- or =N-, and Ring B is a 5-membered heteroarylene, provided that Y 1A 、Y 2A and Y 3A At least one of them is not =C(H)- or =C(R 2A )-;and

[1088] Optionally a carbon-carbon single bond or a carbon-carbon double bond;

[1089] Z A for Where * is the covalent connection point with ether, ** is the covalent connection point with Z 1A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates that at the connection point** and The situation where one bond is a single bond and one bond is a double bond; Z 1A for Where *** is the covalent connection point with indazole, **** is the covalent connection point with Z A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates the connection point **** with A situation where one bond between the two is a single bond and one bond is a double bond; and ring B A It is a 5-membered heteroarylene group.

[1090] 4. The compound of any one of Embodiments 1 to 3 or a pharmaceutically acceptable salt thereof, which has Formula IVA:

[1091]

[1092] in

[1093] Optionally a carbon-carbon single bond or a carbon-carbon double bond;

[1094] Z A for Where * is the covalent connection point with ether, ** is the covalent connection point with Z 1A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates that at the connection point** and The situation where one bond between them is a single bond and one bond is a double bond; Z 1A for Where *** is the covalent connection point with indazole, **** is the covalent connection point with Z A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates the connection point **** with A situation where one bond between the two is a single bond and one bond is a double bond; and ring B A It is a 5-membered heteroarylene group.

[1095] 5. The compound of any one of embodiments 1 to 3, wherein

[1096] X 2A -O-, -S-, -N(H)-, -N(R 1A )-or=N-,X 1A and X 3A are independently -O-, -S-, =C(H)-, =C(R 1A )-、-N(H)-、-N(R 1A )- or =N-, and ring A A is a 5-membered heteroarylene group; and

[1097] Y 2A -O-, -S-, -N(H)-, -N(R 2A )-or=N-,Y 1A and Y 3A are independently -O-, -S-, =C(H)-, =C(R 2A )-、-N(H)-、-N(R 2A )-or=N-, and B A It is a 5-membered heteroarylene group.

[1098] 6. The compound of any one of embodiments 1 to 5 or a pharmaceutically acceptable salt thereof, wherein

[1099] Ring A A is a 5-membered heteroarylene selected from the group consisting of:

[1100]

[1101] Each of these represents a covalent attachment point, and each R 1A Independently as described herein.

[1102] 7. The compound according to any one of embodiments 1 to 6 or a pharmaceutically acceptable salt thereof, wherein Ring A A is a 5-membered heteroarylene selected from the group consisting of:

[1103]

[1104] Each of these represents the covalent attachment point, and R 1A As described herein.

[1105] 8. The compound of any one of embodiments 1 to 6 or a pharmaceutically acceptable salt thereof, wherein Ring A A is a 5-membered heteroarylene selected from the group consisting of:

[1106]

[1107]

[1108] Each of these Indicates the point of covalent attachment.

[1109] 9. A compound according to any one of the preceding embodiments or a pharmaceutically acceptable salt thereof, wherein ring B A is a 5-membered heteroarylene selected from the group consisting of:

[1110]

[1111] Each of these represents a covalent attachment point, and each R 2 Independently as described herein.

[1112] 10. The compound of any one of the preceding embodiments or a pharmaceutically acceptable salt thereof, wherein ring B A is a 5-membered heteroarylene selected from the group consisting of:

[1113]

[1114] Each of these Indicates the point of covalent attachment.

[1115] 11. A compound according to any one of the preceding embodiments or a pharmaceutically acceptable salt thereof, wherein

[1116]

[1117] is ethylene, propylene or butylene, wherein each hydrogen atom in ethylene, propylene and butylene is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a Rb 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, and each Indicates the point of covalent attachment.

[1118] 12. A compound according to any one of the preceding embodiments or a pharmaceutically acceptable salt thereof, wherein one R 3A is C1-C6 alkyl, wherein each hydrogen atom in the C1-C6 alkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e Rf 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2, or R 3A and / or R 4A The two of them, together with the carbon or carbon atoms to which they are attached, are optionally combined to form a C3-C6 cycloalkyl group, a 3-membered to 7-membered heterocycloalkyl group, wherein when R 3A and / or R 4A Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e Rf 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2, and any other R 3A and R 4A For H.

[1119] 13. A compound according to any one of the preceding embodiments or a pharmaceutically acceptable salt thereof, wherein one R 3A is C1-C6 alkyl, wherein each hydrogen atom in the C1-C6 alkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NRe S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2, and any other R 3A and R 4A For H.

[1120] 14. A compound according to any one of the preceding embodiments or a pharmaceutically acceptable salt thereof, wherein one R 3A It is a C1-C6 alkyl group.

[1121] 15. The compound of any one of the preceding embodiments or a pharmaceutically acceptable salt thereof, wherein one R 3A is methyl, and any other R 3A and R 4A For H.

[1122] 16. A compound according to any one of the preceding embodiments, or a pharmaceutically acceptable salt thereof, wherein R 5A and R 6A For H.

[1123] 17. A compound according to any one of the preceding embodiments, or a pharmaceutically acceptable salt thereof, wherein R 7A For H.

[1124] 18. A compound according to any one of the preceding embodiments, or a pharmaceutically acceptable salt thereof, wherein q A is 0.

[1125] 19. The compound of embodiment 1, which is selected from the group consisting of:

[1126]

[1127]

[1128] or a pharmaceutically acceptable salt thereof.

[1129] 20. A pharmaceutical composition comprising a compound according to any one of the preceding embodiments and optionally one or more excipients.

[1130] 21. A method of treating a disease in a subject, comprising administering a therapeutically effective amount of the compound of any one of Examples 1 to 19 or the pharmaceutical composition of Example 20.

[1131] 22. A compound as defined in any one of embodiments 1 to 19 for use in a method of treating a disease in a subject.

[1132] 23. Use of a compound according to any one of embodiments 1 to 19 for the manufacture of a medicament for treating a disease in a subject.

[1133] In some embodiments, Ring A A It is a 5-membered heteroarylene group.

[1134] In some embodiments, Ring A A is a 5-membered heteroarylene group, wherein each R 1A If present, independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C6 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NRc R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2; each R 1A and R 5A or R 6A can be optionally combined with one or more atoms to which it is attached to form a C3-C6 cycloalkyl group, a 3-membered to a 7-membered heterocycloalkyl group, wherein when R 1A and R 5A or R 6A Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: OR e 、OC(O)R e 、OC(O)NR e R f、-OS(O)R e 、OS(O)2R e 、OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、S(O)R e 、-S(O)2R e 、S(O)NR e R f 、S(O)2NR e R f NR e R f NR e C(O)R f 、-NR e C(O)OR f NR e C(O)NR e R f NR e S(O)R f 、-NR e S(O)2R f NR e S(O)NR e R f NR e S(O)2NR e R f 、-C(O)R e 、C(O)OR e 、C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or NO2.

[1135] In some embodiments, Ring A A R 1A and R 5A or R 6A can be optionally combined with one or more atoms to which it is attached to form a C3-C6 cycloalkyl group, a 3-membered to a 7-membered heterocycloalkyl group, wherein when R1A and R 5A or R 6A Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: OR e 、OC(O)R e 、OC(O)NR e R f 、-OS(O)R e 、OS(O)2R e 、OS(O)NR e R f 、OS(O)2NR e R f 、-SR e 、S(O)R e 、-S(O)2R e 、S(O)NR e R f 、-S(O)2NR e R f NR e R f 、-NR e C(O)R f NR e C(O)OR f NR e C(O)NR e R f NR e S(O)R f 、-NR e S(O)2R f NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、C(O)R e 、C(O)OR e 、C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、P(O)OR e 、-P(O)2ORe , -CN or NO2.

[1136] In some embodiments, Ring A A is pyrazolylene, isoxazolylene, isothiazolylene, imidazolylene, wherein each independently optionally 1, 2 or 3 R 1A (m R 1A ) substituted, said R 1A Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a Rb 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NRc S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[1137] In some embodiments, Ring A A Has the following formula:

[1138]

[1139] in is optionally a carbon-carbon single bond or a carbon-carbon double bond, each represents the covalent attachment point, and R 1A and m A As described herein. In some embodiments, Ring A A Has the following formula:

[1140]

[1141] in is optionally a carbon-carbon single bond or a carbon-carbon double bond, each Indicates the covalent attachment point, Ring A A is a 5-membered heteroarylene group, and R 1A and m A As described in this article.

[1142] In some embodiments, Ring A A Has the following formula:

[1143]

[1144] in is optionally a carbon-carbon single bond or a carbon-carbon double bond, each represents the covalent attachment point, X 2 -O-, -S-, -N(H)-, -N(R 1A )-or=N-,X 1A and X 3A are independently -O-, -S-, =C(H)-, =C(R 1A )-、-N(H)-、N(R 1 )- or =N-, and ring A A is a 5-membered heteroarylene group, provided that X 1A 、X 2A and X 3A At least one of them is not =C(H)- or =C(R 1 )-, Ring A A is a 5-membered heteroarylene group, and R 1A and m as described herein.

[1145] In some embodiments, m A is 0, 1, 2 or 3. In some embodiments, m A is 0, 1 or 2. In some embodiments, m A is 0 or 1. In some embodiments, m A is 0. In some embodiments, m A is 1. In some embodiments, m A is 2. In some embodiments, m A is 3.

[1146] In some embodiments, Ring A A is a 5-membered heteroarylene selected from the group consisting of:

[1147]

[1148] Each of these represents a covalent attachment point, and each R 1A Independently as described herein.

[1149] In some embodiments, Ring A A is a 5-membered heteroarylene selected from the group consisting of:

[1150]

[1151] Each of these represents the covalent attachment point, and R 1A As described herein.

[1152] In some embodiments, R 1Ais C1-C6 alkyl, wherein each hydrogen atom in the C1-C6 alkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c Rd 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[1153] In some embodiments, Ring A A is a 5-membered heteroarylene selected from the group consisting of:

[1154]

[1155] Each of these Indicates the point of covalent attachment.

[1156] In some embodiments, Ring B A It is a 5-membered heteroarylene group.

[1157] In some embodiments, Ring B A is a 5-membered heteroarylene group, wherein each R 2A If present, independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C6 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NRa R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2;.

[1158] In some embodiments, Ring B A Has the following formula:

[1159]

[1160] Each of these represents the covalent attachment point, and R 2A and n A As stated in this article,

[1161] where Z A for Where * is the covalent connection point with ether, ** is the covalent connection point with Z 1A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates that at the connection point** and The situation where one bond between them is a single bond and one bond is a double bond; Z 1A for Where *** is the covalent connection point with indazole, **** is the covalent connection point with Z A The covalent attachment point, Represents ring B A The point of covalent attachment of a ring atom of Indicates the connection point **** with The situation where one bond is a single bond and one bond is a double bond.

[1162] In some embodiments, Ring B A Has the following formula:

[1163]

[1164] Each of these Indicates the covalent attachment point, ring B A is a 5-membered heteroarylene group, and Z A , Z 1A 、R 2A and n A As described in this article.

[1165] In some embodiments, Ring B A Has the following formula:

[1166]

[1167] Each of these represents the covalent attachment point, Y 1A 、Y 2A and Y 3A are independently -O-, -S-, =C(H)-, =C(R 2A )-、-N(H)-、-N(R 2A )- or =N-, and Ring B is a 5-membered heteroarylene, provided that Y 1A 、Y 2A and Y 3A At least one of them is not =C(H)- or =C(R 2A )-, and R 2A , Z A , Z 1A and n A As described in this article.

[1168] In some embodiments, Z 1A is N. In some embodiments, Z 1A For C.

[1169] In some embodiments, Ring B A is pyrazolylene, isoxazolylene, isothiazolylene, imidazolylene, each of which is optionally substituted with 1, 2 or 3 R 2A (n A R 2A ) substituted, said R 2A Each of the following is independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-7 membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR cS(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[1170] In some embodiments, n A is 0, 1, 2 or 3. In some embodiments, n A is 0, 1 or 2. In some embodiments, n A is 0 or 1. In some embodiments, n A is 0. In some embodiments, n A is 1. In some embodiments, n A is 2. In some embodiments, n A is 3.

[1171] In some embodiments, Ring B A is a 5-membered heteroarylene selected from the group consisting of:

[1172]

[1173]

[1174] Each of these represents a covalent attachment point, and each R 2A Independently as described herein.

[1175] In some embodiments, Ring B A is a 5-membered heteroarylene selected from the group consisting of:

[1176]

[1177] Each of these Indicates the point of covalent attachment.

[1178] In some embodiments, R 7A are independently H, deuterium, -C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-S(O)2NR c R d 、-P(O)2R c R d 、-P(O)2NR c R d OR-P(O)2OR c .

[1179] In some embodiments, R 7A is independently H.

[1180] In some embodiments, indazole is optionally substituted with 0, 1, or 2 R 8A (q R 8A ) substituted, said R 8A Each is independently selected from the group consisting of: deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NRa S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-C(=N)NR c R d 、-PR c R d 、-P(O)R c R d 、-P(O)2R c R d 、-P(O)NR c R d 、-P(O)2NR c R d 、-P(O)OR c 、-P(O)2OR c , -CN or -NO2.

[1181] In some embodiments, each R 8A If present, it is independently hydrogen.

[1182] In some embodiments, q A is 0, 1 or 2. In some embodiments, q A is 0 or 1. In some embodiments, q A is 0. In some embodiments, q A is 1. In some embodiments, q A is 2.

[1183] In some embodiments,

[1184] is ethylene, propylene or butylene, wherein each hydrogen atom in ethylene, propylene and butylene is optionally substituted independently by deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b 、-PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a Rb 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, and each Indicates the point of covalent attachment.

[1185] In some embodiments, p A is 2, 3 or 4. In some embodiments, p A is 2 or 3. In some embodiments, p A is 2. In some embodiments, p A is 3. In some embodiments, p A is 4.

[1186] In some embodiments, an R 3A is C1-C6 alkyl, wherein each hydrogen atom in the C1-C6 alkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2, or R 3A and / or R 4A The two of them, together with the carbon or carbon atoms to which they are attached, are optionally combined to form a C3-C6 cycloalkyl group, a 3-membered to 7-membered heterocycloalkyl group, wherein when R 3A and / or R 4A Each hydrogen atom in the C3-C6 cycloalkyl or 3- to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2, and any other R 3 and R 4 For H.

[1187] In some embodiments, an R 3A is C1-C6 alkyl, wherein each hydrogen atom in the C1-C6 alkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NRe R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f 、-PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2, and any other R 3 and R 4 For H.

[1188] In some embodiments, an R 3A In some embodiments, one R 3A is methyl, and any other R 3A and R 4A For H.

[1189] In some embodiments, R 5A and R 6A For H.

[1190] In some embodiments, the present disclosure provides a compound selected from the group consisting of:

[1191] (17E)-16-Ethyl-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[1192] 2-[(17E)-8,16-dimethyl-2,10,11,13-tetrahydro-3,5-vinyl-bridged [1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazol-14(8H)-yl]-N-ethylacetamide;

[1193] (17E)-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[1194] (17E)-8,14,16-trimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[1195] (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole;

[1196] (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadecafluoro[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile;

[1197] (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]oxazole;

[1198] (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]oxazole-16-carbonitrile;

[1199] (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole;

[1200] (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole-16-carbonitrile;

[1201] (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole;

[1202] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile;

[1203] (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]thiazole;

[1204] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile;

[1205] (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]thiazole-16-carbonitrile;

[1206] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[6,5-d][1,2]oxazole-16-carbonitrile;

[1207] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[6,5-d][1,2]thiazole-16-carbonitrile;

[1208] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecafluoro[5,6-c][1,2]oxazole-16-carbonitrile;

[1209] (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[5,6-c][1,2]thiazole-16-carbonitrile;

[1210] or a pharmaceutically acceptable salt thereof.

[1211] Pharmaceutical composition

[1212] For therapeutic purposes, pharmaceutical compositions comprising the compounds described herein may further comprise one or more pharmaceutically acceptable excipients. Pharmaceutically acceptable excipients are non-toxic and otherwise biologically suitable substances for administration to an individual. Such excipients facilitate administration of the compounds described herein and are compatible with the active ingredient. Examples of pharmaceutically acceptable excipients include stabilizers, lubricants, surfactants, diluents, antioxidants, adhesives, colorants, bulking agents, emulsifiers, or flavor modifiers. In a preferred embodiment, the pharmaceutical compositions of the present disclosure are sterile compositions. Pharmaceutical compositions can be prepared using compounding techniques known or available to those skilled in the art.

[1213] The present disclosure also contemplates sterile compositions, including compositions that comply with national and regional regulations governing such compositions.

[1214] The pharmaceutical compositions and compounds described herein can be formulated into solutions, emulsions, suspensions or dispersions in suitable pharmaceutical solvents or carriers, or formulated into pills, tablets, lozenges, suppositories, sachets, dragees, granules, powders, powders for reconstitution or capsules together with solid carriers according to conventional methods known in the art for preparing various dosage forms. The pharmaceutical compositions of the present disclosure can be administered by a suitable delivery route (e.g., oral, parenteral, rectal, nasal, topical or ocular routes) or by inhalation. Preferably, the composition is formulated for intravenous or oral administration.

[1215] For oral administration, the compounds of the present disclosure can be provided in solid form (e.g., tablets or capsules) or in the form of solutions, emulsions, or suspensions. To prepare oral compositions, the compounds of the present disclosure can be formulated to produce, for example, a dosage of about 0.1 mg to 1 g per day, or about 1 mg to 50 mg per day, or about 50 to 250 mg per day, or about 250 mg to 1 g per day. Oral tablets may include active ingredients mixed with, for example, the following pharmaceutically acceptable compatible excipients: diluents, disintegrants, binders, lubricants, sweeteners, flavorings, colorants, and preservatives. Suitable inert fillers include sodium carbonate and calcium carbonate, sodium phosphate and calcium phosphate, lactose, starch, sugar, glucose, methylcellulose, magnesium stearate, mannitol, sorbitol, etc. Exemplary liquid oral excipients include ethanol, glycerol, water, etc. Starch, polyvinyl-pyrrolidone (PVP), sodium starch glycolate, microcrystalline cellulose, and alginic acid are exemplary disintegrants. Binders may include starch and gelatin. If present, the lubricant may be magnesium stearate, stearic acid or talc.If necessary, tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate to delay absorption in the gastrointestinal tract, or may be provided with an enteric coating.

[1216] Capsules for oral administration include hard gelatin capsules and soft gelatin capsules. To prepare hard gelatin capsules, the active ingredient can be mixed with a solid, semisolid or liquid diluent. Soft gelatin capsules can be prepared by mixing the active ingredient with water, oil (e.g., peanut oil or olive oil), liquid paraffin, a mixture of monoglycerides and diglycerides of short-chain fatty acids, polyethylene glycol 400 or propylene glycol.

[1217] Liquids for oral administration may be in the form of suspensions, solutions, emulsions or syrups or may be lyophilized or presented as dry products for reconstitution with water or other suitable vehicles before use. Such liquid compositions may optionally contain: pharmaceutically acceptable excipients, such as suspending agents (e.g., sorbitol, methylcellulose, sodium alginate, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel, etc.); non-aqueous vehicles, such as oils (e.g., almond oil or fractionated coconut oil), propylene glycol, ethanol or water; preservatives (e.g., methylparaben or propylparaben or sorbic acid); wetting agents, such as lecithin; and, if necessary, flavorings or coloring agents.

[1218] For parenteral use, including intravenous, intramuscular, intraperitoneal, intranasal or subcutaneous routes, the medicament of the present disclosure can be buffered to a sterile aqueous solution or suspension form of appropriate pH value and isotonicity or provided in the form of an oil acceptable to parenteral. Suitable aqueous vehicles include Ringer's solution and isotonic sodium chloride. Such forms can be provided in unit dosage form (e.g., ampoule or disposable injection device), multiple dose form (e.g., a vial from which an appropriate dose can be taken out), or a solid form or pre-concentrate form that can be used to prepare an injectable formulation. Over a period of several minutes to several days, an illustrative infusion dose is within the range of about 1 to 1000 μg / kg of the medicament per minute and a mixture of a pharmaceutical carrier.

[1219] For nasal, inhaled, or oral administration, the pharmaceutical compositions of the present disclosure may be administered using, for example, a spray formulation also containing a suitable carrier. The compositions of the present disclosure may be formulated for rectal administration in the form of a suppository.

[1220] For topical administration, the compounds of the present disclosure are preferably formulated as a cream or ointment or a similar vehicle suitable for topical administration. For topical administration, the compounds of the present disclosure can be mixed with a pharmaceutical carrier at a concentration of drug:vehicle of about 0.1% to about 10%. Ano...

Claims

1. A compound of formula I in Ring A is a 5- to 10-membered heteroarylene group or a C6-C 10 arylene; Ring B is a 5-membered heteroarylene group; Each L is independently -O-, -S-, -S(O)-, -S(O)2-, -N(R 5 )C(O)-、-C(O)N(R 5 )-、-N(R 5 )-、-N(R 5 )S(O)-、-S(O)N(R 5 )-、-N(R 5 )S(O)2-、-S(O)2N(R 5 )-or-C(R 6 )(R 7 )-, provided that (L) p Does not contain OO, SO or NN bonds; Each R 1 , R 2 and R 3 If present, it is independently deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b , -PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c 、-C(O)OR c 、 -C(O)NR c R d 、 -C(=N)NR c R d 、 -PR c R d 、 -P(O)R c R d 、 -P(O)2R c R d 、 -P(O)NR c R d 、 -P(O)2NR c R d 、 -P(O)OR c 、 -P(O)2OR c 、 -CN or -NO2; R 4 H, deuterium, -C(O)R c 、-C(O)OR c 、-C(O)NR c R d 、-P(O)2R c R d 、-P(O)2NR c R d 、-P(O)2OR c Or -S(O)2OR c ; Each R 5 If present, it is independently H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 aryl or 5- to 10-membered heteroaryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl or 5- to 10-membered heteroaryl group is independently optionally substituted with: -OR c 、-OC(O)R c 、-OC(O)NR c R d 、-OC(=N)NR c R d 、-OS(O)R c 、-OS(O)2R c 、-OS(O)NR c R d 、-OS(O)2NR c R d 、-SR c 、-S(O)R c 、-S(O)2R c 、-S(O)NR c R d 、-S(O)2NR c R d 、-NR c R d 、-NR c C(O)R d 、-N(C(O)R c )(C(O)R d ),-NR c C(O)OR d 、-NR c C(O)NR c R d 、-NR c C(=N)NR c R d 、-NR c S(O)R d 、-NR c S(O)2R d 、-NR c S(O)NR c R d 、-NR c S(O)2NR c R d 、-C(O)R c , -C(O)OR c , -C(O)NR c R d , -C(=N)NR c R d , -PR c R d , -P(O)R c R d , -P(O)2R c R d , -P(O)NR c R d , -P(O)2NR c R d , -P(O)OR c , -P(O)2OR c , -CN or -NO2; Each R 6 and R 7 are independently H, deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, -OR a 、-OC(O)R a 、-OC(O)NR a R b 、-OS(O)R a 、-OS(O)2R a 、-SR a 、-S(O)R a 、-S(O)2R a 、-S(O)NR a R b 、-S(O)2NR a R b 、-OS(O)NR a R b 、-OS(O)2NR a R b 、-NR a R b 、-NR a C(O)R b 、-NR a C(O)OR b 、-NR a C(O)NR a R b 、-NR a S(O)R b 、-NR a S(O)2R b 、-NR a S(O)NR a R b 、-NR a S(O)2NR a R b 、-C(O)R a 、-C(O)OR a 、-C(O)NR a R b , -PR a R b 、-P(O)R a R b 、-P(O)2R a R b 、-P(O)NR a R b 、-P(O)2NR a R b 、-P(O)OR a 、-P(O)2OR a , -CN or -NO2, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3-membered to 7-membered heterocycloalkyl, C6-C 10 Each hydrogen atom in the aryl and 5- to 10-membered heteroaryl groups is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f , -PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2; or R 5 , R 6 and R 7 The two of them, together with one or more atoms to which they are attached, are optionally combined to form a C3-C6 cycloalkyl group, a 3-membered to 7-membered heterocycloalkyl group, wherein when R 5 , R 6 and R 7 Each hydrogen atom in the C3-C6 cycloalkyl or 3-membered to 7-membered heterocycloalkyl formed when the two are combined together is independently optionally substituted by the following groups: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f , -PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2; Each R a , R b , R c , R d , R e and R f independently selected from the group consisting of: H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10 aryl, 5- to 10-membered heteroaryl, and C1-C6 alkylene-5- to 10-membered heteroaryl, or R a and R b or R c and R d or R e and R f Together with the atoms to which they are attached, they form a 3- to 7-membered heterocycloalkyl group, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C 10 Aryl, C1-C6 alkylene-C6-C 10 Each hydrogen atom in the aryl, 5- to 10-membered heteroaryl, or C1-C6 alkylene-5- to 10-membered heteroaryl is independently optionally substituted with deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -OC1-C6 alkyl, -OC(O)-(H or C1-C6 alkyl), -OC(O)N(H or C1-C6 alkyl)2, -OC(O)N(C2-C6 alkylene), -OS(O)-(H or C1-C6 alkyl), -OS(O)2-(H or C1-C6 alkyl), -OS(O)N(H or C1-C6 alkyl)2, -OS(O)N(C2-C6 alkylene), -OS(O)2N(H or C1-C6 alkyl)2, - S(O)2N(C2-C6 alkylene), -S(H or C1-C6 alkyl), -S(O)(H or C1-C6 alkyl), -S(O)2(H or C1-C6 alkyl), -S(O)N(H or C1-C6 alkyl)2, -S(O)N(C2-C6 alkylene), -S(O)2N(H or C1-C6 alkyl)2, -S(O)2N(C2-C6 alkylene), -N(H or C1-C6 alkyl)2, -N(C2-C6 alkylene), -N(H or C1-C6 alkyl)C(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)O(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)C(O)N( H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)C(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)-(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)2(H or C1-C6 alkyl), -N(H or C1-C6 alkyl)S(O)N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)N(C2-C6 alkylene), -N(H or C1-C6 alkyl)S(O)2N(H or C1-C6 alkyl)2, -N(H or C1-C6 alkyl)S(O)2N(C2-C6 alkylene), -C(O)-(H or C1-C6 alkyl), -C(O)O -C(O)N(C2-C6 alkylene), -P(H or C1-C6 alkyl)2, -P(C2-C6 alkylene), -P(O)(H or C1-C6 alkyl)2, -P(O)(C2-C6 alkylene), -P(O)2(H or C1-C6 alkyl)2, -P(O)2(C2-C6 alkylene), -P(O)N(H or C1-C6 alkyl)2, -P(O)N(C2-C6 alkylene), -P(O)2N(H or C1-C6 alkyl)2, -P(O)2N(C2-C6 alkylene), -P(O)O(H or C1-C6 alkyl), -P(O)2O(H or C1-C6 alkyl), -CN or -NO2; m is 0, 1, 2, 3 or 4; n is 0, 1, 2 or 3; p is 4, 5, 6, 7, 8 or 9; and q is 0, 1, or 2; or a pharmaceutically acceptable salt thereof; Provided that the compound does not have the formula: or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein (L) p Does not contain -NR covalently linked directly to ring A 5 C(O)-.

3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein ring A is C6-C 10 The arylene group is an arylene group, and m is 0, 1 or 2.

4. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein ring A is phenylene and m is 0, 1 or 2.

5. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein ring A is phenylene and m is 0 or 1.

6. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein ring A is phenylene, m is 1, and R 1 Methyl, ethyl, F, Cl, Br, -CN, Each of these Indicates the point of covalent attachment.

7. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring A is Each of these Indicates the point of covalent attachment. 8 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring A is a 5- to 10-membered heteroarylene group, and m is 0, 1, 2 or 3. 9 . The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring A is a 5- to 10-membered heteroarylene group, and m is 0, 1 or 2.

10. A compound according to any one of claims 1 to 3 or 9 or a pharmaceutically acceptable salt thereof having formula II: Wherein Y is a single bond, a double bond, -O-, -S-, =C(H)-, =C(R 1 )-、-N(H)-、-N(R 1 )- or =N-, and Ring A is a 5- to 10-membered heteroarylene group.

11. A compound according to any one of claims 1 to 3, 9 or 10, or a pharmaceutically acceptable salt thereof, having formula III: Where Z is Where * is the same as (L) p The covalent attachment point of Z is 1 The covalent attachment point of represents a point of covalent attachment to a ring atom of Ring A, and Indicates that at the connection point ** and The situation where one bond is a single bond and one bond is a double bond; Z 1 for Among them, *** is The covalent connection point of , **** is the covalent connection point with Z, represents a point of covalent attachment to a ring atom of Ring A, and Indicates the connection point **** with The condition where one bond between them is a single bond and one bond is a double bond, provided that Z and Z 1 are not nitrogen atoms; and Ring A is a 5- to 10-membered heteroarylene group.

12. A compound according to any one of claims 1 to 3 or 9 to 11 or a pharmaceutically acceptable salt thereof having formula IV: in X 1 , X 2 and X 3 are independently -O-, -S-, =C(H)-, =C(R 1 )-、-N(H)-、-N(R 1 )- or = N-, provided that X 1 , X 2 and X 3 At least one of them is not =C(H)- or =C(R 1 )-; Z is Where * is the same as (L) p The covalent attachment point of Z is 1 The covalent attachment point of represents a point of covalent attachment to a ring atom of Ring A, and Indicates that at the connection point ** and The situation where one bond is a single bond and one bond is a double bond; Z 1 for Among them, *** is The covalent connection point of , **** is the covalent connection point with Z, represents a point of covalent attachment to a ring atom of Ring A, and Indicates the connection point **** with The condition where one bond between them is a single bond and one bond is a double bond, provided that Z and Z 1 are not nitrogen atoms; and Ring A is a 5- to 10-membered heteroarylene group.

13. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroarylene group selected from the group consisting of: Each of these Indicates the point of covalent attachment.

14. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroarylene group selected from the group consisting of: Each of these Indicates the point of covalent attachment.

15. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5- to 10-membered heteroarylene group selected from the group consisting of: Each of these Indicates the point of covalent attachment.

16. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring B is a 5-membered heteroarylene selected from the group consisting of: Each of these Indicates the point of covalent attachment.

17. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring B is a 5-membered heteroarylene selected from the group consisting of: Each of these Indicates the point of covalent attachment.

18. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein Ring B is a 5-membered heteroarylene selected from the group consisting of: Each of these Indicates the point of covalent attachment.

19. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein q is 0, 1 or 2.

20. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein q is 0 or 1.

21. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 3 For F.

22. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 4 It is H or methyl.

23. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each L is independently -C(R 6 )(R 7 )-, -C(O)-, -O- or -N(R 5 )-, provided that (L) p Does not contain -OO- or -ON(R 5 )-key, and (L) p The point of covalent attachment to ring A does not form an -NN- or -ON- bond.

24. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein - (L) p -for-CR 6 R 7 -O(CR 6 R 7 )2O-、-CR 6 R 7 -O(CR 6 R 7 )3O-、-(CR 6 R 7 )C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )N(R 5 )C(O)-(CR 6 R 7 )2-、-O(CR 6 R 7 )2N(R 5 )C(O)-(CR 6 R 7 )O-、-N(R 5 )-C(O)(CR 6 R 7 )2O(CR 6 R 7 )2-、-CR 6 R 7 O(CR 6 R 7 )2O-(CR 6 R 7 )2.-O(CR 6 R 7 )2O(CR 6 R 7 )2O-、-CR 6 R 7 O-CR 6 R 7 -C(O)N(R 5 )-(CR 6 R 7 )2-、-(CR 6 R 7 )3O(CR 6 R 7 )2-、-(CR 6 R 7 )2O(CR 6 R 7 )3-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )4O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )2-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3O-、-CR 6 R 7 -N(R 5 )-(CR 6 R 7 )3-、-O(CR 6 R 7 )2O-CR 6 R 7 -、-O(CR 6 R 7 )2O(CR 6 R 7 )2-、-O(CR 6 R 7 )2O(CR 6 R 7 )3-、-(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )3-、-O(CR 6 R 7 )2-N(R 5 )-CR 6 R 7 -、-(CR 6 R 7 )2-N(R 5 )-(CR 6 R 7 )2-、-O-(CR 6 R 7 )2-、-O-(CR 6 R 7 )3-, -O-(CR 6 R 7 )4-, -O-(CR 6 R 7 )5-, -O-(CR 6 R 7 )2O-, -O-(CR 6 R 7 )3O-, -O-(CR 6 R 7 )4O- or -O-(CR 6 R 7 )5O-.

25. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each R 5 are independently H, methyl, ethyl, -C(O)CH3 or -C(O)CH2CH3; or R 5 If it exists, and R 6 or R 7 If present, then together with the one or more atoms to which it is attached, form a 3- to 7-membered heterocycloalkyl group; wherein when R 5 and R 6 or R 7 Each hydrogen atom in the 3- to 7-membered heterocycloalkyl formed when combined together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f , -PR e R f ,-P(O)R e R f ,-P(O)2R e R f ,-P(O)NR e R f ,-P(O)2NR e R f ,-P(O)OR e ,-P(O)2OR e ,-CN or -NO2.

26. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 6 and R 7 If present, then together with the one or more atoms to which it is attached, form a 3- to 7-membered heterocycloalkyl group; wherein when R 6 and R 7 Each hydrogen atom in the 3- to 7-membered heterocycloalkyl formed when combined together is independently optionally substituted with: -OR e 、-OC(O)R e 、-OC(O)NR e R f 、-OS(O)R e 、-OS(O)2R e 、-OS(O)NR e R f 、-OS(O)2NR e R f 、-SR e 、-S(O)R e 、-S(O)2R e 、-S(O)NR e R f 、-S(O)2NR e R f 、-NR e R f 、-NR e C(O)R f 、-NR e C(O)OR f 、-NR e C(O)NR e R f 、-NR e S(O)R f 、-NR e S(O)2R f 、-NR e S(O)NR e R f 、-NR e S(O)2NR e R f 、-C(O)R e 、-C(O)OR e 、-C(O)NR e R f , -PR e R f 、-P(O)R e R f 、-P(O)2R e R f 、-P(O)NR e R f 、-P(O)2NR e R f 、-P(O)OR e 、-P(O)2OR e , -CN or -NO2.

27. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 5 or R 7 Each R combined together 6 are independently H or C1-C6 alkyl.

28. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R 5 or R 7 Combined with an R 6 is methyl, and the remaining R 6 and R 7 For H.

29. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein - (L) p - is -O-(CH2)2O-CH2-, -OC(H)(CH3)-CH2-O-CH2-, -CH2O-(CH2)2O-, -C(H)(CH3)-O-(CH2)2O-, -CH2N(H)-(CH2)2O-, -CH2N(CH3)-(CH2)2O-, -CH2N(CH2CH3)-(CH2)2O-, -O(CH2)2N(H)CH2-, -O(CH2)2N(CH3)CH2-, -OCH2-C(H)(CH3)-N(CH(CH3)2)CH2-, -OCH2-C(H)(CH2F)-N(CH3)CH2-, -OCH2-C(H)(CH2CH3)-N(CH3)CH2-, -O(CH2)2N(C(O)CH3)CH2-, -OC(H)(CH3)CH2N(H)CH2-, -OC(H)(CH3)CH2N(CH3)CH2-, -OC(H)(CH2CN)CH2N(CH3)CH2-, -OC(H)(CH2CH3)CH2N(CH3)CH2-, -OC(H)(CH2F)CH2N(CH3)CH2-, -OC(H)(CHF2)CH2N(CH3)CH2-, -OC(H)(CH2OH)CH2N(CH3)CH2-, -OC(H)(CH3)C(O)N(CH3)CH2-, -OC(H)(cyclobutyl)CH2N(CH3)CH2-, -OC(H)(CH3)CH2N(CH2CH3)CH2-, -OC(H)(CH3)CH2N(CH(CH3)2)-CH2-, -OC(H)(CH3)CH2N(CH3)-C(H)(CH3)-, -OC(H)(CH3)CH2N(oxetan-3-yl)-CH2-, -OC(H)(CH3)CH2N(cyclopropyl)-CH2-, -OCH2C(H)(CH3)N(cyclopropyl)-CH2-, -OC(H)(CH3)CH2N(C(O)CH3)CH2-, -O(C(H)(CH3))CH2N(C(O)CH2CH3)CH2-, -CH2N(H)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-C(H)(CH3)-CH2O-, -CH2N(CH3)-(CH2)2(C(H)CH3)CH2O-, -CH2N(CH3)-(CH2)-(C(H)CH3)O-, -O(CH2)2-, -O(CH2)3-, -O(CH2)4-, -O(CH2)3O-, -O(CH2)4O-, -O(CH2)5O-, -O-(C(H)(CH3)-(CH2)2O-, -O(CH2)2-C(H)(CH3)-O-,-O(CH2)2C(H)(CH3)CH2O-, -O(CH2)3C(H)(CH3)CH2O-, -O(CH2)2N(H)C(O)-(CH2)O-, -O(CH2)2N(CH3)C(O)-(CH2)O-, -O(CH2)2O(CH2)2O-, -OC(H)(CH3)CH2OCH2-, -O(CH2)2OCH2C(H)(CH3)O-, -O(CH2)2OC(H)(CH3)-CH2O-, 30. A compound selected from the group consisting of: (11E)-1-methyl-1,18,19,21-tetrahydro-8H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-f][1,4,12,13]benzodioxadiazacyclooctadecane; (11E)-1-[(Methylsulfonyl)methyl]-19,20-dihydro-1H,8H,18H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-f][1,5,12,13]benzodioxadiazacyclooctadecane; (11E)-1-methyl-18,19,20,21-tetrahydro-1H,8H-10,7,4-(ethyl[1]yl[1,2]diylidene)pyrazolo[3,4-g][1,6,13,14]benzodioxadiazacyclononadecanone; (10R,16E)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-3-methyl-13-[(4-methylpiperazin-1-yl)methyl]-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-13-[(dimethylamino)methyl]-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-3-methyl-13-(1-methylpiperidin-4-yl)-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-13-(2-methoxypropan-2-yl)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-3-methyl-13-(4-methylpiperazin-1-yl)-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-14-fluoro-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-14-(2-hydroxypropan-2-yl)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-14-{(2S)-2-[(methylsulfonyl)methyl]azetidin-1-yl}-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-etheno-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-25-one; (10R,16E)-3-methyl-25-oxo-3,5,6,9,10,19-hexahydro-8H-20,22-etheno-7,10-carboxadipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecan-14-carbonitrile; and (10R,16E)-3-methyl-3,5,6,9,10,19-hexahydro-8H-20,22-ethenyl-7,10-methanodipyrazolo[3,4-i:4',3'-m][1,8,5]benzodioxazacyclooctadecane; or a pharmaceutically acceptable salt thereof.

31. A compound selected from the group consisting of: (18E)-8-methyl-N-(propan-2-yl)-8,9,11,12-tetrahydro-2H-3,5-ethylenedipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadeca[5,6-b]pyridine-16-carboxamide; (18E)-N,8-dimethyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadeca[5,6-b]pyridine-16-carboxamide; (18E)-N,N,8-trimethyl-8,9,11,12-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadeca[5,6-b]pyridine-16-carboxamide; (18E)-N-ethyl-8-methyl-8,9,11,12-tetrahydro-2H-3,5-ethylenedipyrazolo[3',4':9,10;4",3":13,14][1,4]dioxacyclopentadeca[5,6-b]pyridine-16-carboxamide; (10S,18E)-8,10,16-trimethyl-2,8,11,12-tetrahydro-10H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,5]dioxacyclopentadeca[7,6-b]pyridine; (10S,18E)-17-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-ethylenedipyrazolo[3,4-j:4',3'-n]pyrido[4,3-f][1,4]oxazacyclopentadecane; and (10S,18E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-ethylene-bridged bipyrazolo[3,4-j:4',3'-n]pyrido[3,2-f][1,4]oxazacyclopentadecane; or a pharmaceutically acceptable salt thereof.

32. A compound selected from the group consisting of: (17E)-8,14,16-trimethyl-2,8,9,11,12,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[11,10-c:15,14-c':6,7-c"]tripyrazole; 2-[(17E)-8,9,16-trimethyl-8,9,11,12-tetrahydro-3,5-etheno[1,4]dioxacyclopentadeca[11,10-c:15,14-c':6,7-c"]tripyrazol-14(2H)-yl]ethan-1-ol; (17E)-8,14,16-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (17E)-19-Fluoro-8,14,16-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (17E)-16-ethyl-8,14-dimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-2-methylpropan-2-ol; 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]propan-2-one; 2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethan-1-ol; (17E)-8,16-dimethyl-14-[2-(pyrrolidin-1-yl)ethyl]-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (3S)-1-{2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethyl}pyrrolidin-3-ol; (17E)-16-ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (10S,17E)-8,10,14,16-tetramethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (10R,17E)-8,10,14,16-tetramethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (12S,17E)-16-ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (12R,17E)-16-ethyl-8,12,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (10S,17E)-16-ethyl-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (10S,17E)-16-cyclopropyl-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (17E)-16-(methoxymethyl)-8,14-dimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (17E)-8,14,16-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 1-[(17E)-8,14,16-trimethyl-2,8,10,11,13,14-hexahydro-12H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one; (17E)-8,12,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-6,8,12,14,16-pentamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-16-ethyl-8,12,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-7,14,16-trimethyl-2,10,11,12,13,14-hexahydro-7H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-7,12,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-7H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (17E)-8,14,16-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-8,10,14,16-tetramethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(17E)-8,16-dimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(17E)-8,10,16-trimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(17E)-10-ethyl-8,16-dimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (19E)-8,13,16,18-Tetramethyl-2,11,12,13,14,16-hexahydro-8H,10H-3,5-etheno[1,7]dioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazole; 2-[(19E)-8,13,18-trimethyl-2,8,11,12,13,14-hexahydro-10H,16H-3,5-etheno[1,7]dioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazol-16-yl]ethan-1-ol; (19E)-8,16,18-trimethyl-2,11,12,16-tetrahydro-8H,10H-3,5-ethene-bridged tripyrazolo[3,4-h:3',4'-l:4",3"-p][1,7,4]dioxazacycloheptadecan-13(14H)-one; (19E)-8,12,16,18-tetramethyl-2,11,12,16-tetrahydro-8H,10H-3,5-ethene-bridged tripyrazolo[3,4-h:3',4'-l:4",3"-p][1,7,4]dioxazacycloheptadecan-13(14H)-one; (13R,19E)-8,13,16,18-tetramethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazole; (13S,19E)-8,13,16,18-tetramethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazole; 2-[(19E)-8,13,18-trimethyl-2,8,10,11,13,14-hexahydro-16H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazol-16-yl]ethan-1-ol; (19E)-8,13,18-Trimethyl-16-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole; (3S)-1-{2-[(17E)-16-ethyl-8-methyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]ethyl}pyrrolidin-3-ol; (19E)-22-Fluoro-8,16,18-trimethyl-2,10,11,13,14,16-hexahydro-8H-3,5-etheno[1,4,7]trioxacycloheptadeca[12,13-c:17,16-c':8,9-c"]tripyrazole; 3-[(17E)-16-ethyl-8-methyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-N,N-dimethylpropan-1-amine; (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]pyrrolidin-3-ol; (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-1-methylpyrrolidin-3-ol; (3R,4S)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]oxolan-3-ol; (3S,4R)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]oxolan-3-ol; (rac)-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutan-1-ol; (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]piperidin-3-ol; (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-1-methylpiperidin-3-ol; (rac)-1,5-anhydro-2,3-dideoxy-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-L-threopentitol; (rac)-1,5-anhydro-2,4-dideoxy-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]-L-threopentitol; (12R,17E)-8,10,12,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; (12S,17E)-8,10,12,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; (rac)-(3S,4S)-1-methyl-4-[(17E)-8,10,16-trimethyl-2,8,9,10,11,12-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]pyrrolidin-3-ol; (11S,17E)-8,11,14,16-tetramethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-8,9,16-trimethyl-14-[2-(pyrrolidin-1-yl)ethyl]-2,8,9,11,12,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[11,10-c:15,14-c':6,7-c"]tripyrazole; [(10S,17E)-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-16-yl]methanol; N 1 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutyl}-N- 1 ,N 2 ,N 2 -trimethylethylene-1,2-diamine; (11S,17E)-8,10,11,14,16-pentamethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; N 2 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,14H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14-yl]cyclobutyl}-N- 1 ,N 1 -dimethylethylene-1,2-diamine; (10R,15E)-3,12,14-trimethyl-5,6,9,10,12,18-hexahydro-3H,8H-19,21-ethenyl-7,10-methanotripyrazolo[3,4-i:3',4'-m:4",3"-q][1,8,4]dioxazacyclooctadecan-24-one; (17E)-16-ethyl-8,10,14-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-10-ethyl-8,14,16-trimethyl-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-8,10,16-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-19-fluoro-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (17E)-8,10,16-trimethyl-14-(1-methylpyrrolidin-3-yl)-2,9,10,11,12,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (10S,17E)-8,10,12,14,16-pentamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10R,19E)-8,16,18-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecane; (2S)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-2-ol; 2-[(10S,17E)-19-chloro-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (2R)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-2-ol; 2-[(10S,17E)-16-ethyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-12-ethyl-8,10,16-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (10S,17E)-8,10,12,14-tetramethyl-16-[(piperidin-4-yl)oxy]-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10R,19E)-18-ethoxy-8-methyl-2,10,11,12,13,15-hexahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol; 2-[(10S,17E)-6,8,10,12,16-pentamethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (10S,17E)-8,10,14,16-tetramethyl-12-(oxetan-3-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-16-ethoxy-6,8,10-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (10S,17E)-16-{[1-(methylsulfonyl)piperidin-4-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,13R,17E)-8,10,12,13,14,16-hexamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,13S,17E)-8,10,12,13,14,16-hexamethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-{(10S,17E)-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; (10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol; (10S,17E)-16-[(azetidin-3-yl)oxy]-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-16-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-16-ethoxy-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(17E)-10-cyclobutyl-8,12,16-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (10S,17E)-8,10,12,14-tetramethyl-16-{[(3S)-pyrrolidin-3-yl]oxy}-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-16-{[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (2S)-2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; (10S,17E)-16-ethoxy-8,10,14-trimethyl-12-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,14-trimethyl-2,11,12,14-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile; (10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-16-carbonitrile; (10R,19E)-18-ethoxy-8,16-dimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecane; (10S,17E)-12-cyclopropyl-8,10,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,12,14-tetramethyl-16-(2,2,2-trifluoroethoxy)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; {[(10S,17E)-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile; (10S,17E)-10,14,16-trimethyl-8-[(methylthio)methyl]-12-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-12-ethyl-8,10,14,16-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-16-ethoxy-8-ethyl-10,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-{(10S,17E)-8-ethyl-10,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; (2R)-2-[(10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; 2-[(10S,17E)-16-ethoxy-19-fluoro-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-16-{[1-(methylsulfonyl)piperidin-4-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (10S,19E)-8,16,18-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecane; 2-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-{(10S,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-[(10S,17E)-16-{[(3S)-1-(methylsulfonyl)pyrrolidin-3-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-16-bromo-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-{(10S,17E)-16-[(azetidin-3-yl)oxy]-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol; (10S,17E)-16-{[3-(methylsulfonyl)cyclobutyl]oxy}-8,10,12,14-tetramethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,19E)-18-ethoxy-8,16-dimethyl-2,8,11,12,15,16-hexahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecan-13(10H)-one; (10R,19E)-18-ethoxy-8,16-dimethyl-2,8,11,12,15,16-hexahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecan-13(10H)-one; 2-[(10R,19E)-18-ethoxy-22-fluoro-8-methyl-2,10,11,12,13,15-hexahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol; 2-{(11S,17E)-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10R,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(11S,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10R,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-[(10R,17E)-12-cyclopropyl-16-ethoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10R,17E)-16-ethoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(11S,17E)-12-cyclopropyl-16-ethoxy-8,11-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10R,19E)-22-fluoro-8-methyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol; (2S)-2-{(10S,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol; 2-{(11S,17E)-6,8,11-trimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10R,17E)-6,8,10-trimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; {[(10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile; 2-[(10R,17E)-12-cyclopropyl-16-ethoxy-6,8,10-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(11S,17E)-12-cyclopropyl-16-ethoxy-6,8,11-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (10S,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (2S)-2-{(10R,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol; (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-16-carbonitrile; (10S,17E)-12-ethyl-8,10,14-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol; (10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol; 2-[(10S,17E)-19-fluoro-8,10,12-trimethyl-16-(2,2,2-trifluoroethoxy)-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-{(10R,17E)-12-cyclopropyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(11S,17E)-12-cyclopropyl-8,11-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; (2S)-2-[(10S,17E)-16-ethoxy-19-fluoro-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; (2S)-2-[(10S,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; 2-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 1-[(10R,17E)-16-ethoxy-14-(2-hydroxyethyl)-8,10-dimethyl-2,8,10,11,13,14-hexahydro-12H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one; Ethyl [(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]acetate; (2S)-2-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol; (10S,17E)-14-(2-hydroxyethyl)-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,12,13,14-tetrahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-11(10H)-one; 2-[(10S,17E)-16-{[1-(methylsulfonyl)azetidin-3-yl]oxy}-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 1-[(10S,17E)-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]-2-methylpropan-2-ol; 2-{(10S,13R,17E)-8,10,12,13-tetramethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10S,13S,17E)-8,10,12,13-tetramethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(17E)-10-(fluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(17E)-11-(Fluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; (2S)-1-{(10R,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol; (2S)-2-[(11S,17E)-16-ethoxy-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; (2S)-2-[(10R,17E)-16-ethoxy-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; (2S)-2-{(11S,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol; (2S)-2-{(10R,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-1-ol; 2-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}acetamide; (10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2-(propan-2-yl)-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-ol; 2-[(8aR,19E)-1-(cyclopropylmethoxy)-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; (10R,18E)-17-ethoxy-8,15-dimethyl-2,8,11,12,14,15-hexahydro-10H-3,5-etheno-10,13-methanotripyrazolo[3,4-g:3',4'-k:4",3"-o][1,5]oxazacyclohexadecanol; {(17E)-14-(2-hydroxyethyl)-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,10,11,12,13,14-hexahydro-7H-3,5-ethenyltripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-7-yl}acetonitrile; (17E)-16-ethoxy-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno-10,12-methanotripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-16-ethoxy-19-fluoro-6,8,10-trimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(8aR,9R,19E)-1-ethoxy-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(8aR,9S,19E)-1-ethoxy-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(19E)-18-Ethoxy-8,21-dimethyl-2,10,11,12,13,15-hexahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol; 2-[(8aR,9R,19E)-1-ethoxy-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(8aR,9S,19E)-1-ethoxy-22-fluoro-9,11-dimethyl-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(19E)-18-Ethoxy-22-fluoro-8,21-dimethyl-2,10,11,12,13,15-hexahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol; 2-{(10S,17E)-8-cyclopropyl-10,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; (10S,13S,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecane; (10R,13R,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecane; (10R,13S,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-vinyl-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecane; (10S,13R,19E)-18-ethoxy-8,13,16-trimethyl-2,8,10,11,12,13,15,16-octahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-l:4",3"-p][1,6]oxazacycloheptadecane; 2-{(10R,17E)-19-fluoro-8,10,12-trimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-[(8aR,9S,19E)-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(8aR,9R,19E)-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(19E)-8,21-dimethyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol; 2-[(8aR,9R,19E)-22-fluoro-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(8aR,9S,19E)-22-fluoro-9,11-dimethyl-1-[(propan-2-yl)oxy]-7,8,8a,9,11,17-hexahydro-6H-14,16-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-3(4H)-yl]ethan-1-ol; 2-[(19E)-22-Fluoro-8,21-dimethyl-18-[(propan-2-yl)oxy]-2,10,11,12,13,15-hexahydro-3,5-etheno-10,14-methanotripyrazolo[3,4-h:3',4'-1:4",3"-p][1,6]oxazacycloheptadecan-16(8H)-yl]ethan-1-ol; 2-{(10R,17E)-10-(hydroxymethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-[(11S,17E)-16-ethoxy-11-ethyl-8,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-16-ethoxy-10-ethyl-8,12-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-16-(methoxymethyl)-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}-2-methylpropan-2-ol; 1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-one; (10R,17E)-14-(2-hydroxyethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-10-carbonitrile; 2-{(10S,17E)-8,10,12-trimethyl-16-[(methylamino)methyl]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10S,17E)-16-[(dimethylamino)methyl]-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol: (2R)-2-{[(10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}propionitrile; (2S)-2-{[(10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenyltrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}propionitrile; 2-[(4aS,7aS,13E)-12-ethoxy-3,6,8-trimethyl-4a,5,6,7,7a,8,9,16-octahydro-17,19-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecan-10(3H)-yl]ethan-1-ol; 2-[(4aR,7aR,13E)-12-ethoxy-3,6,8-trimethyl-4a,5,6,7,7a,8,9,16-octahydro-17,19-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecan-10(3H)-yl]ethan-1-ol; {[(8aR,19E)-3-(2-hydroxyethyl)-9,11-dimethyl-3,4,7,8,8a,9,11,17-octahydro-6H-14,16-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-1-yl]oxy}acetonitrile; {[(8aR,9R,19E)-3-(2-hydroxyethyl)-9,11-dimethyl-3,4,7,8,8a,9,11,17-octahydro-6H-14,16-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[2,1-c][1,4]oxazacyclopentadecan-1-yl]oxy}acetonitrile; 2-{(10S,17E)-10-(difluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10R,17E)-10-(difluoromethyl)-8,12-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10S,17E)-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-[(10R,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (4aS,7aS,13E)-12-ethoxy-3,8,10-trimethyl-3,4a,5,6,7,7a,8,9,10,16-decahydro-17,19-ethylene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecane; (4aR,7aR,13E)-12-ethoxy-3,8,10-trimethyl-3,4a,5,6,7,7a,8,9,10,16-decahydro-17,19-ethylene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n]pyrrolo[3,4-b][1,4]oxazacyclopentadecane; (2S)-1-{(10S,17E)-12-ethyl-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol; 2-{(11R,17E)-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-{(10S,17E)-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}ethan-1-ol; 2-[(11R,17E)-16-ethoxy-19-fluoro-8,11-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-16-ethoxy-19-fluoro-8,10-dimethyl-12-(propan-2-yl)-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; {[(10S,17E)-19-fluoro-14-(2-hydroxyethyl)-8,10,12-trimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethenetrispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-16-yl]oxy}acetonitrile; 2-[(10R,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (2S)-2-[(10R,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; 2-[(10S,17E)-16-ethoxy-12-ethyl-19-fluoro-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (2S)-2-[(10R,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; (10S,17E)-16-ethoxy-12-ethyl-14-(2-hydroxyethyl)-8,10-dimethyl-2,10,11,12,13,14-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane-6-carbonitrile; 2-[(10S,17E)-16-ethoxy-6-ethynyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; 2-[(10S,17E)-16-(ethylamino)-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (2S)-1-{(10S,17E)-12-ethyl-19-fluoro-8,10-dimethyl-16-[(propan-2-yl)oxy]-2,8,10,11,12,13-hexahydro-14H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl}propan-2-ol; 2-[(10S,17E)-6-amino-16-ethoxy-12-ethyl-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]ethan-1-ol; (2S)-2-[(10S,17E)-12-ethyl-19-fluoro-16-methoxy-8,10-dimethyl-2,8,10,11,12,13-hexahydro-14H-3,5-ethene-trispyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-14-yl]propan-1-ol; 2,2'-[(10S,17E)-10,12-dimethyl-16-[(propan-2-yl)oxy]-10,11,12,13-tetrahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-8,14(2H)-diyl]di(ethan-1-ol); (17E)-16-ethyl-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; 2-[(17E)-8,16-dimethyl-2,10,11,13-tetrahydro-3,5-etheno[1,4]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-14(8H)-yl]-N-ethylacetamide; (17E)-8,14-dimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile; (17E)-8,14,16-trimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (10S,17E)-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-vinyl[1,4]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole-16-carbonitrile; (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadeca[6,5-d][1,2]oxazole-16-carbonitrile; (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadeca[6,5-d][1,2]thiazole-16-carbonitrile; (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadecano[5,6-c][1,2]oxazole-16-carbonitrile; (10S,17E)-10,14-dimethyl-10,11,13,14-tetrahydro-2H-3,5-ethylene-bridged bipyrazolo[4',3':13,14;4",3":9,10][1,4]dioxacyclopentadeca[5,6-c][1,2]thiazole-16-carbonitrile; and (10S,17E)-16-ethyl-8,10,14-trimethyl-2,8,10,11,13,14-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; or a pharmaceutically acceptable salt thereof.

33. A compound selected from the group consisting of: (17E)-8,15,16-trimethyl-2,8,9,11,12,15-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[11,10-c:15,14-c':6,7-c"]tripyrazole; (17E)-8,15,16-trimethyl-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]propan-2-one; 1-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-2-methylpropan-2-ol; 2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]ethan-1-ol; (17E)-8,16-dimethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; (10S,17E)-8,10,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (17E)-8,15,16-trimethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 1-[(17E)-8,15,16-trimethyl-2,8,10,11,13,15-hexahydro-12H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one; (17E)-8,12,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 1-[(10S,17E)-8,10,15,16-tetramethyl-2,8,10,11,13,15-hexahydro-12H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]ethan-1-one; (10S,17E)-8,10,12,15,16-pentamethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 2-[(10S,17E)-8,10,16-trimethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]ethan-1-ol; 2-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]ethan-1-ol; (10S,17E)-12-ethyl-8,10,15,16-tetramethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 1-[(10S,17E)-8,10,15,16-tetramethyl-2,8,10,11,13,15-hexahydro-12H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-12-yl]propan-1-one; 2-[(19E)-8,13,18-trimethyl-2,8,11,12,13,14-hexahydro-10H,17H-3,5-etheno[1,7]dioxacycloheptadecano[12,13-c:17,16-c':8,9-c"]tripyrazol-17-yl]ethan-1-ol; (13E)-3-methyl-3,5,6,7,8,16-hexahydro-9,12-(nitrene)-17,19-ethylene-bridged bipyrazolo[3,4-1:4',3'-p][1,6]oxazaheterocycloheptadecanol; (18E)-8-methyl-2,8,10,11,12,13-hexahydro-3,5-ethylenetriazolo[1,5-f:3',4'-j:4",3"-n][1,6]oxazacyclopentadecane; (17E)-15-(2-methoxyethyl)-8,16-dimethyl-2,11,12,15-tetrahydro-8H,10H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazole; 2-[(17E)-8,9,16-trimethyl-8,9,11,12-tetrahydro-3,5-etheno[1,4]dioxacyclopentadeca[11,10-c:15,14-c':6,7-c"]tripyrazol-15(2H)-yl]ethan-1-ol; (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]piperidin-3-ol; (rac)-4-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-1-methylpiperidin-3-ol; (17E)-8,9,16-trimethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,8,9,11,12,15-hexahydro-3,5-etheno[1,4]dioxacyclopentadeca[11,10-c:15,14-c':6,7-c"]tripyrazole; (rac)-1,5-anhydro-2,3-dideoxy-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-L-threopentitol; 1,5-Anhydro-2,4-dideoxy-2-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]-L-threopentitol; (10S,17E)-8,10,12,16-tetramethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,12,16-tetramethyl-15-[2-(4-methylpiperazin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (20E)-8,18-dimethyl-2,8,11,12-tetrahydro-10H-3,5-ethylene-bridged bipyrazolo[3",4":10',11';4"',3"':14',15'][1,5]dioxacyclopentadecano[6',7':3,4]pyrazolo[1,5-a]pyrazin-19(18H)-one; (10S,17E)-8,10,12,16-tetramethyl-15-[2-(morpholin-4-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; 4-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]butan-2-ol; N 1 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]cyclobutyl}-N- 1 ,N 2 ,N 2 -trimethylethylene-1,2-diamine; 2-Methyl-4-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]butan-2-ol; 2-Methyl-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol; N 2 -{(1s,3s)-3-[(17E)-8,16-dimethyl-2,8,11,12-tetrahydro-10H,15H-3,5-etheno[1,5]dioxacyclopentadeca[10,11-c:15,14-c':6,7-c"]tripyrazol-15-yl]cyclobutyl}-N- 1 ,N 1 -dimethylethylene-1,2-diamine; (17E)-8,10,16-trimethyl-15-(1-methylpyrrolidin-3-yl)-2,9,10,11,12,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:4',3'-j:4",3"-n][1,4]oxazacyclopentadecane; (10R,17E)-8,10,12,16-tetramethyl-15-[2-(pyrrolidin-1-yl)ethyl]-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (2S)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol; (10S,17E)-8,10,12,14,15-pentamethyl-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (2R)-1-[(10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-15H-3,5-ethenetripyrazolo[3,4-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecan-15-yl]propan-2-ol; (10S,17E)-8,10,12,14,16-pentamethyl-2,10,11,12,13,16-hexahydro-8H-3,5-ethene-bridged tripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl[1,2]oxazolo[3,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl[1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,12,16-tetramethyl-2,8,10,11,12,13-hexahydro-3,5-ethylene-bridged bipyrazolo[3,4-j:4',3'-n][1,2]thiazolo[3,4-f][1,4]oxazacyclopentadecane; (10S,20E)-18-[2-(methylsulfonyl)ethyl]-8,10,12-trimethyl-2,8,10,11,12,13,16,17,18,19-decahydro-3,5-ethylene-bridged pyrazino[1',2':1,5]pyrazolo[3,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10S,17E)-16-cyclopropyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl[1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10S,17E)-16-ethyl-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-vinyl[1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,12-trimethyl-16-(propan-2-yl)-2,8,10,11,12,13-hexahydro-3,5-vinyl[1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,12-trimethyl-16-(propan-2-yl)-2,8,10,11,12,13-hexahydro-3,5-vinyl[1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10S,17E)-16-ethoxy-8,10,12-trimethyl-2,8,10,11,12,13-hexahydro-3,5-etheno[1,2]oxazolo[5,4-f]dipyrazolo[3,4-j:4',3'-n][1,4]oxazacyclopentadecane; (10R,17E)-8,10,14,15-tetramethyl-12-(propan-2-yl)-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,14,15-tetramethyl-12-(propan-2-yl)-2,10,11,12,13,15-hexahydro-8H-3,5-ethene-bridged tripyrazolo[4,3-f:3',4'-j:4",3"-n][1,4]oxazacyclopentadecane; (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadeca[7,6-d][1,2]oxazole; (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]oxazole-16-carbonitrile; (10S,17E)-8,10,16-trimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole; (10S,17E)-8,10-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[7,6-d][1,2]thiazole-16-carbonitrile; (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadeca[6,7-c][1,2]oxazole; (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile; (10S,17E)-8,10,16-trimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadeca[6,7-c][1,2]thiazole; (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole-16-carbonitrile; (10S,17E)-8,10-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadeca[6,7-c][1,2]thiazole-16-carbonitrile; (17E)-8,16-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]oxazole; (17E)-8,16-dimethyl-2,10,11,13-tetrahydro-8H-3,5-ethylenedipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadeca[7,6-d][1,2]oxazole; and (17E)-8,16-dimethyl-2,8,10,11-tetrahydro-13H-3,5-ethylene-bridged bipyrazolo[3',4':10,11;4",3":14,15][1,4]dioxacyclopentadecano[6,7-c][1,2]thiazole; or a pharmaceutically acceptable salt thereof.

34. A pharmaceutical composition comprising a compound according to any one of the preceding claims and optionally one or more excipients.

35. A method of treating a disease in a subject comprising administering a therapeutically effective amount of a compound according to any one of claims 1 to 33 or a pharmaceutical composition according to claim 35.

36. A compound according to any one of claims 1 to 33 for use in a method of treating a disease in a subject.

37. Use of a compound according to any one of claims 1 to 33 for the manufacture of a medicament for treating a disease in a subject.

Images