Biaryl amides with modified sugar groups for treatment of diseases associated with heat shock protein pathways

Abstract

Compounds based on biaryl amides and coumarins having modified sugar groups for use in the treatment of diseases associated with heat shock protein pathways are provided. The compounds have the formula wherein the variables are as defined herein. Also provided are pharmaceutical compositions of the compounds of Formulae (I), (II), (III), (IV) and (V). These biaryl amide and coumarin-based derivatives with modified sugar groups are useful for the treatment and prevention of diseases and disorders, including neurological disorders such as neurodegenerative diseases and neurological injury disorders, such as diabetic peripheral neuropathy. # imgabs0 #

Description

[0001] This application is a divisional application of the Chinese invention patent application with application number 201980046311.2 after the PCT international application with PCT application number PCT / US2019 / 032292 entered the Chinese national phase, with application date May 14, 2019, and invention name “Bis(r)ylamides with modified sugar groups for treating diseases related to heat shock protein pathways”.

[0002] This application claims the benefit of priority to U.S. Provisional Application No. 62 / 671,047, filed May 14, 2018, the entire contents of which are hereby incorporated by reference. Technical Field

[0003] The present invention relates generally to the fields of biology, chemistry and medicine. More specifically, the present invention relates to compounds, compositions and methods for treating and preventing diseases and disorders, including neurological disorders such as neurodegenerative diseases, and nerve-damaging disorders such as diabetic peripheral neuropathy. Background Art

[0004] Heat shock protein 90 (Hsp90) is associated with a variety of disorders caused by the misfolding of one or more proteins. These disorders include neurological diseases associated with damage, loss of function or death of neurons. These diseases may affect peripheral neurons (peripheral neuropathy) or central neurons (central neuropathy) and may be caused by systemic diseases or conditions such as diabetes, leprosy, vitamin deficiency, drug treatment or immune system diseases, or by conditions such as viral infections or traumatic injuries. The damage to peripheral neurons caused by diabetes is called diabetic peripheral neuropathy and can result in nerve damage to any organ of the body. This condition can cause a variety of different symptoms, but the hallmark symptoms are chronic pain, numbness and tingling, especially at the distal end. In 2010, it was believed that approximately 132 million people suffered from diabetic peripheral neuropathy, which is the most common complication of diabetes and is also the main source of morbidity and mortality in diabetes.

[0005] Neckers and colleagues reported that the DNA gyrase inhibitors, novobiocin and related natural products, bind to gyrase with low affinity (IC 50∼700 μM) binds to the C-terminal nucleotide-binding pocket of Hsp90 (Marcu et al., 2000) while retaining similar biological activity. Previous studies have demonstrated that the coumarin core of novobiocin can be replaced with a biphenyl core (Kusuma et al., 2012). Although the original biphenyl analog contained a novobiocin sugar moiety, this sugar group is synthetically challenging, requiring up to ten steps to obtain (Yu et al., 2005b; Beaver et al., 2008; Zhao et al., 2011). Furthermore, glycosylation of activated novobiocin with a biphenyl moiety produces a mixture of anomers, increasing the difficulty of obtaining a single anomer. Therefore, there is commercial interest in replacing this group without sacrificing activity or other pharmacological properties. Furthermore, alternative groups that exhibit other beneficial properties, such as improved activity, stability, solubility, or any subset of these and / or other properties, are important for developing compounds with the potential to treat and / or prevent diseases or disorders, including those associated with Hsp90. Binding to the C-terminus of Hsp90 may have therapeutic advantages compared to inhibitors that bind to the N-terminus (Kusuma, 2012). In particular, there remains a need for additional compounds with unique biological and pharmacological properties for the treatment of diseases and disorders associated with heat shock protein pathways, including inhibition of Hsp90 and / or induction of Hsp70. Summary of the Invention

[0006] The present disclosure provides biaryl Hsp90 inhibitors containing modified ether groups with therapeutic properties, pharmaceutical compositions thereof, methods for their preparation, and methods for their use.

[0007] In certain aspects, the present disclosure provides compounds of the formula:

[0008]

[0009] in:

[0010] n is 0, 1, or 2;

[0011] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0012] Y2 is CH2, O or S;

[0013] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6), alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0014] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0015] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0016] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0017] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0018] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0019] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0020] R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl(C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0021] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0022] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0023] X1 is CR 14 or N, where:

[0024] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0025] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0026] X2 is CR 15 or N, where:

[0027] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino(C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0028] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0029] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0030] Or a compound of the formula:

[0031]

[0032] in:

[0033] n is 0, 1, or 2;

[0034] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0035] Y2 is CH2, O or S;

[0036] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0037] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6), alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0038] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0039] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0040] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0041] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0042] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0043] R7 is hydrogen, carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0044] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12);

[0045] R8 and R9 are each independently hydrogen, halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0046] R 10 is amino or alkylamino (C≤6) , dialkylamino (C≤12) , acylamino (C≤12) or a substituted form of any of these three groups;

[0047] X1 is CR 14 or N, where:

[0048] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0049] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0050] X2 is CR 15 or N, where:

[0051] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0052] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl(C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0053] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0054] Or a compound of the formula:

[0055]

[0056] in:

[0057] n is 0, 1, or 2;

[0058] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0059] Y2 is CH2, O or S;

[0060] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0061] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0062] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0063] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0064] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0065] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0066] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0067] R7 is carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0068] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0069] R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl(C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0070] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0071] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0072] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0073] X1 is CR 14 or N, where:

[0074] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0075] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0076] X2 is CR 15 or N, where:

[0077] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8)or a substituted form of any of these groups;

[0078] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0079] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0080] Or a compound of the formula:

[0081]

[0082] in:

[0083] n is 0, 1, or 2;

[0084] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0085] Y2 is CH2 or S;

[0086] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0087] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0088] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0089] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0090] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0091] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0092] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0093] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0094] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0095] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7)- or a substituted form of any of these groups;

[0096] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0097] X1 is CR 14 or N, where:

[0098] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0099] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0100] X2 is CR 15 or N, where:

[0101] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0102] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0103] R15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0104] Or a compound of the formula:

[0105]

[0106] in:

[0107] n is 0, 1, or 2;

[0108] Y1 is a substituted -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -;

[0109] Y2 is CH2, O or S;

[0110] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0111] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0112] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0113] R3 is -NR 11 R 11 ' or -C(O)NR12 R 12 ',in:

[0114] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0115] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0116] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0117] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0118] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0119] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0120] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12)or a substituted form of any of these groups;

[0121] X1 is CR 14 or N, where:

[0122] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0123] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0124] X2 is CR 15 or N, where:

[0125] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0126] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0127] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0128] Or a compound of the formula:

[0129]

[0130] in:

[0131] n is 1 or 2;

[0132] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0133] Y2 is CH2, O or S;

[0134] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0135] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0136] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0137] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0138] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0139] R12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0140] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0141] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0142] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0143] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0144] X1 is CR 14 or N, where:

[0145] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0146] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6), alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0147] X2 is CR 15 or N, where:

[0148] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0149] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0150] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0151] Or a compound of the formula:

[0152]

[0153] in:

[0154] n is 0, 1, or 2;

[0155] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0156] Y2 is CH2, O or S;

[0157] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6)or a substituted form of any of these groups;

[0158] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0159] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0160] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0161] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0162] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0163] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0164] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic(C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0165] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0166] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0167] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0168] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0169] R8 is halogen, alkoxy (C3-6) , acyloxy (C≤6) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0170] R9 and R 10 are each independently halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0171] X1 is CR 14 or N, where:

[0172] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl(C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0173] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0174] X2 is CR 15 or N, where:

[0175] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0176] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0177] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0178] Or a compound of the formula:

[0179]

[0180] in:

[0181] n is 0, 1, or 2;

[0182] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0183] Y2 is CH2, O or S;

[0184] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0185] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0186] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0187] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0188] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) ;

[0189] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0190] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy(C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0191] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0192] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0193] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0194] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0195] X1 is CR 14 or N, where:

[0196] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0197] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl(C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0198] X2 is CR 15 or N, where:

[0199] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0200] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0201] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0202] Or a compound of the formula:

[0203]

[0204] in:

[0205] n is 0, 1, or 2;

[0206] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0207] Y2 is CH2, O or S;

[0208] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6), alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0209] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0210] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0211] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0212] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0213] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0214] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0215] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl(C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0216] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0217] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0218] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0219] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0220] R8 is halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0221] X1 is CR 14 or N, where:

[0222] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy(C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0223] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0224] X2 is CR 15 or N, where:

[0225] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0226] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0227] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0228] Or a compound of the formula:

[0229]

[0230] in:

[0231] R 16 is an alkyl group (C≤12) , cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or its substituted form;

[0232] R 17and R 18 are independently hydrogen, alkyl (C≤8) or substituted alkyl (C≤8) ;

[0233] R 19 Is a carboxyl or alkyl group (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0234] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or replaced

[0235] R 19 ' is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0236] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0237] R 20 、R 21 and R 22 are each independently halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups, or a protected hydroxyl group;

[0238] or a pharmaceutically acceptable salt of any one of the above formulae.

[0239] In certain embodiments, the compound is further defined as:

[0240]

[0241] in:

[0242] n is 0, 1, or 2;

[0243] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0244] Y2 is CH2, O or S;

[0245] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0246] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0247] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0248] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0249] R11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0250] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0251] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0252] R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0253] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0254] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0255] X1 is CR 14 or N, where:

[0256] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6), alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0257] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0258] X2 is CR 15 or N, where:

[0259] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0260] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0261] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0262] Or a compound of the formula:

[0263]

[0264] in:

[0265] n is 0, 1, or 2;

[0266] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0267] Y2 is CH2, O or S;

[0268] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0269] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0270] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0271] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0272] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0273] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0274] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy(C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0275] R7 is hydrogen, carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0276] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0277] R8 and R9 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0278] R 10 is amino or alkylamino (C≤6) , dialkylamino (C≤12) , acylamino (C≤12) or a substituted form of any of these three groups;

[0279] X1 is CR 14 or N, where:

[0280] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0281] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl(C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0282] X2 is CR 15 or N, where:

[0283] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0284] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0285] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0286] Or a compound of the formula:

[0287]

[0288] in:

[0289] n is 0, 1, or 2;

[0290] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0291] Y2 is CH2, O or S;

[0292] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6)or a substituted form of any of these groups;

[0293] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0294] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0295] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0296] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0297] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0298] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0299] R7 is carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic(C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0300] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0301] R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0302] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0303] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0304] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0305] X1 is CR 14 or N, where:

[0306] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8)or a substituted form of any of these groups; or

[0307] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0308] X2 is CR 15 or N, where:

[0309] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0310] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0311] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0312] Or a compound of the formula:

[0313]

[0314] in:

[0315] n is 0, 1, or 2;

[0316] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0317] Y2 is CH2 or S;

[0318] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl(C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0319] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0320] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0321] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0322] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0323] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0324] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0325] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0326] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0327] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0328] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0329] X1 is CR 14 or N, where:

[0330] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0331] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0332] X2 is CR 15 or N, where:

[0333] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0334] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0335] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0336] Or a compound of the formula:

[0337]

[0338] in:

[0339] n is 0, 1, or 2;

[0340] Y1 is a substituted -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -;

[0341] Y2 is CH2, O or S;

[0342] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0343] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0344] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0345] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0346] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0347] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0348] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0349] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl(C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0350] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0351] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0352] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0353] X1 is CR 14 or N, where:

[0354] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0355] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0356] X2 is CR 15 or N, where:

[0357] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6),-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0358] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0359] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0360] Or a compound of the formula:

[0361]

[0362] in:

[0363] n is 1 or 2;

[0364] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0365] Y2 is CH2, O or S;

[0366] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0367] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl(C≤6) or a substituted form of any of these groups;

[0368] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0369] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0370] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0371] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0372] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0373] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0374] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0375] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0376] X1 is CR 14 or N, where:

[0377] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0378] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0379] X2 is CR 15 or N, where:

[0380] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0381] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0382] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0383] Or a compound of the formula:

[0384]

[0385] in:

[0386] n is 0, 1, or 2;

[0387] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0388] Y2 is CH2, O or S;

[0389] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0390] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0391] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0392] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0393] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6)or substituted acyl (C≤6) ;

[0394] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0395] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0396] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0397] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0398] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0399] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0400] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7)- or a substituted form of any of these groups;

[0401] R8 is an alkoxy group (C3-6) , acyloxy (C≤6) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0402] R9 and R 10 Each independently is hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0403] X1 is CR 14 or N, where:

[0404] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0405] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0406] X2 is CR 15 or N, where:

[0407] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0408] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6), alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0409] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0410] Or a compound of the formula:

[0411]

[0412] in:

[0413] n is 0, 1, or 2;

[0414] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0415] Y2 is CH2, O or S;

[0416] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0417] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0418] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0419] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0420] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) ;

[0421] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0422] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0423] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0424] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0425] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0426] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl(C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0427] X1 is CR 14 or N, where:

[0428] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0429] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0430] X2 is CR 15 or N, where:

[0431] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0432] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0433] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0434] Or a compound of the formula:

[0435]

[0436] in:

[0437] n is 0, 1, or 2;

[0438] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0439] Y2 is CH2, O or S;

[0440] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0441] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0442] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0443] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0444] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0445] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0446] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0447] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0448] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0449] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0450] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0451] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0452] R8 is halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0453] X1 is CR 14 or N, where:

[0454] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0455] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0456] X2 is CR 15 or N, where:

[0457] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0458] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0459] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0460] Or a compound of the formula:

[0461]

[0462] in:

[0463] R 16 is an alkyl group (C≤12) , cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or its substituted form;

[0464] R 17 and R 18 are independently hydrogen, alkyl (C≤8) or substituted alkyl (C≤8) ;

[0465] R 19 is an alkyl group (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) or a substituted form of any of these groups;

[0466] R 20 、R 21 and R 22 Each independently is hydroxyl, alkoxy (C≤12) , substituted alkoxy (C≤12) or protected hydroxyl groups;

[0467] or a pharmaceutically acceptable salt of any one of the above formulae.

[0468] In certain embodiments, the compound is further defined as:

[0469]

[0470] in:

[0471] n is 0, 1, or 2;

[0472] Y1 is -alkanediyl(C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0473] Y2 is CH2, O or S;

[0474] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0475] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0476] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0477] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0478] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0479] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0480] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0481] R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0482] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0483] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0484] X1 is CR 14 or N, where:

[0485] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0486] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6)or a substituted form of any of these groups; and

[0487] X2 is CR 15 or N, where:

[0488] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0489] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0490] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0491] Or a compound of the formula:

[0492]

[0493] in:

[0494] n is 0, 1, or 2;

[0495] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0496] Y2 is CH2, O or S;

[0497] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0498] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0499] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0500] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0501] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0502] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0503] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0504] R7 is carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl(C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0505] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0506] R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0507] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0508] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0509] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0510] X1 is CR 14 or N, where:

[0511] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0512] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0513] X2 is CR 15 or N, where:

[0514] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0515] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0516] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0517] Or a compound of the formula:

[0518]

[0519] in:

[0520] n is 0, 1, or 2;

[0521] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0522] Y2 is CH2 or S;

[0523] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl(C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0524] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0525] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0526] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0527] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0528] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0529] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0530] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0531] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0532] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0533] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0534] X1 is CR 14 or N, where:

[0535] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0536] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0537] X2 is CR 15or N, where:

[0538] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0539] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0540] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0541] Or a compound of the formula:

[0542]

[0543] in:

[0544] n is 0, 1, or 2;

[0545] Y1 is a substituted -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -;

[0546] Y2 is CH2, O or S;

[0547] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0548] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl(C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0549] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0550] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0551] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0552] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0553] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0554] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl(C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0555] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0556] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0557] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0558] X1 is CR 14 or N, where:

[0559] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0560] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0561] X2 is CR 15 or N, where:

[0562] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8)or a substituted form of any of these groups;

[0563] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0564] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0565] Or a compound of the formula:

[0566]

[0567] in:

[0568] n is 1 or 2;

[0569] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0570] Y2 is CH2, O or S;

[0571] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0572] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0573] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0574] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0575] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0576] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0577] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0578] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0579] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0580] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7)- or a substituted form of any of these groups;

[0581] X1 is CR 14 or N, where:

[0582] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0583] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0584] X2 is CR 15 or N, where:

[0585] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0586] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0587] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0588] Or a compound of the formula:

[0589]

[0590] in:

[0591] n is 0, 1, or 2;

[0592] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0593] Y2 is CH2, O or S;

[0594] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0595] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0596] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0597] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0598] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0599] R12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0600] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0601] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0602] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0603] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0604] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;or

[0605] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0606] R8 is an alkoxy group (C3-6), acyloxy (C≤6) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0607] R9 and R 10 Each independently is hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0608] X1 is CR 14 or N, where:

[0609] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0610] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0611] X2 is CR 15 or N, where:

[0612] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0613] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0614] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0615] Or a compound of the formula:

[0616]

[0617] in:

[0618] n is 0, 1, or 2;

[0619] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0620] Y2 is CH2, O or S;

[0621] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0622] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0623] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0624] R3 is -NR 11 R 11' or -C(O)NR 12 R 12 ',in:

[0625] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) ;

[0626] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0627] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0628] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0629] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[0630] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0631] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0632] X1 is CR 14 or N, where:

[0633] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0634] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0635] X2 is CR 15 or N, where:

[0636] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0637] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0638] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0639] Or a compound of the formula:

[0640]

[0641] in:

[0642] n is 0, 1, or 2;

[0643] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0644] Y2 is CH2, O or S;

[0645] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0646] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0647] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0648] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0649] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0650] R 12 and R12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0651] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0652] R8 is hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0653] X1 is CR 14 or N, where:

[0654] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0655] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0656] X2 is CR 15 or N, where:

[0657] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0658] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0659] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0660] Or a compound of the formula:

[0661]

[0662] in:

[0663] R 16 is an alkyl group (C≤12) , cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or its substituted form;

[0664] R 17 and R 18 are independently hydrogen, alkyl (C≤8) or substituted alkyl (C≤8) ;

[0665] R 19 is an alkyl group (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) or a substituted form of any of these groups;

[0666] R 20 、R 21 and R 22 Each independently is hydroxyl, alkoxy (C≤12) , substituted alkoxy (C≤12) or protected hydroxyl groups;

[0667] or a pharmaceutically acceptable salt of any one of the above formulae.

[0668] In certain embodiments, the compound is further defined as:

[0669]

[0670] in:

[0671] n is 0, 1, or 2;

[0672] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0673] Y2 is CH2, O or S;

[0674] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0675] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0676] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0677] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0678] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6)or substituted acyl (C≤6) ;

[0679] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0680] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0681] R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0682] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0683] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0684] X1 is CR 14 or N, where:

[0685] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl(C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0686] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0687] X2 is CR 15 or N, where:

[0688] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) 、

[0689] -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0690] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0691] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0692] or a pharmaceutically acceptable salt of said formula.

[0693] In certain embodiments, the compound is further defined as:

[0694]

[0695] in:

[0696] n is 0, 1, or 2;

[0697] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6)- or a substituted form of any of these groups;

[0698] Y2 is CH2, O or S;

[0699] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0700] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0701] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0702] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0703] R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0704] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;and

[0705] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl(C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0706] or a pharmaceutically acceptable salt of said formula.

[0707] In certain embodiments, the compound is further defined as:

[0708]

[0709] in:

[0710] n is 0, 1, or 2;

[0711] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0712] Y2 is CH2, O or S;

[0713] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0714] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0715] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0716] R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0717] R13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;and

[0718] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0719] or a pharmaceutically acceptable salt of said formula.

[0720] In certain embodiments, the compound is further defined as:

[0721]

[0722] in:

[0723] n is 0, 1, or 2;

[0724] R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0725] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;and

[0726] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0727] or a pharmaceutically acceptable salt of said formula.

[0728] In other embodiments, the compound is further defined as:

[0729]

[0730] in:

[0731] n is 0, 1, or 2;

[0732] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0733] Y2 is CH2, O or S;

[0734] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0735] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0736] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0737] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0738] R 11and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0739] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0740] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0741] R7 is hydrogen, carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0742] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0743] R8 and R9 are each independently hydrogen, halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0744] R 10 is amino or alkylamino (C≤6) , dialkylamino (C≤12) , acylamino (C≤12) or a substituted form of any of these three groups;

[0745] X1 is CR 14 or N, where:

[0746] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0747] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0748] X2 is CR 15 or N, where:

[0749] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0750] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0751] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0752] or a pharmaceutically acceptable salt of said formula.

[0753] In certain embodiments, the compound is further defined as:

[0754]

[0755] in:

[0756] n is 0, 1, or 2;

[0757] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0758] Y2 is CH2, O or S;

[0759] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0760] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0761] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0762] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0763] R7 is hydrogen, carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0764] R 13 is an alkyl group (C≤12) , substituted alkyl(C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0765] R8 and R9 are each independently hydrogen, halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0766] R 10 is amino or alkylamino (C≤6) , dialkylamino (C≤12) , acylamino (C≤12) or a substituted form of any of these three groups;

[0767] or a pharmaceutically acceptable salt thereof.

[0768] In certain embodiments, the compound is further defined as:

[0769]

[0770] in:

[0771] n is 0, 1, or 2;

[0772] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0773] Y2 is CH2, O or S;

[0774] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0775] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0776] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0777] R7 is hydrogen, carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0778] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0779] R8 and R9 are each independently hydrogen, halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0780] R 10 is amino or alkylamino (C≤6) , dialkylamino (C≤12) , acylamino (C≤12) or a substituted form of any of these three groups;

[0781] or a pharmaceutically acceptable salt thereof.

[0782] In certain embodiments, the compound is further defined as:

[0783]

[0784] in:

[0785] n is 0, 1, or 2;

[0786] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0787] Y2 is CH2, O or S;

[0788] R3 is -NR 11 R 11 ' or -C(O)NR 12 R12 ',in:

[0789] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0790] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0791] R7 is hydrogen, carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0792] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0793] R8 and R9 are each independently hydrogen, halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0794] R 10 is amino or alkylamino (C≤6) , dialkylamino (C≤12) , acylamino (C≤12) or a substituted form of any of these three groups;

[0795] or a pharmaceutically acceptable salt thereof.

[0796] In other embodiments, the compound is further defined as:

[0797]

[0798] in:

[0799] n is 0, 1, or 2;

[0800] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0801] Y2 is CH2, O or S;

[0802] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0803] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0804] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0805] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0806] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0807] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0808] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0809] R7 is carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0810] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0811] R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0812] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0813] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0814] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0815] X1 is CR 14 or N, where:

[0816] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0817] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0818] X2 is CR 15 or N, where:

[0819] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0820] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6)or a substituted form of any of these groups; or

[0821] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0822] or a pharmaceutically acceptable salt of said formula.

[0823] In certain embodiments, the compound is further defined as:

[0824]

[0825] in:

[0826] n is 0, 1, or 2;

[0827] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0828] Y2 is CH2, O or S;

[0829] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0830] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0831] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0832] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0833] R7 is carboxyl or alkyl (C3-8) , alkenyl(C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0834] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0835] R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0836] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0837] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0838] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0839] or a pharmaceutically acceptable salt of said formula.

[0840] In certain embodiments, the compound is further defined as:

[0841]

[0842] in:

[0843] n is 0, 1, or 2;

[0844] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0845] Y2 is CH2, O or S;

[0846] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0847] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0848] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0849] R7 is carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0850] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0851] R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8), alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0852] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0853] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0854] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0855] or a pharmaceutically acceptable salt of said formula.

[0856] In certain embodiments, the compound is further defined as:

[0857]

[0858] in:

[0859] n is 0, 1, or 2;

[0860] R7 is carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0861] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0862] R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0863] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0864] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0865] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0866] or a pharmaceutically acceptable salt of said formula.

[0867] In other embodiments, the compound is further defined as:

[0868]

[0869] in:

[0870] n is 0, 1, or 2;

[0871] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6)- or a substituted form of any of these groups;

[0872] Y2 is CH2 or S;

[0873] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0874] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0875] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0876] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0877] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0878] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0879] R4, R5 and R6 are each independently hydrogen, halogen, alkyl(C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0880] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0881] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0882] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0883] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0884] X1 is CR 14 or N, where:

[0885] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0886] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0887] X2 is CR 15 or N, where:

[0888] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0889] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[0890] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0891] or a pharmaceutically acceptable salt of said formula.

[0892] In other embodiments, the compound is further defined as:

[0893]

[0894] in:

[0895] n is 0, 1, or 2;

[0896] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0897] Y2 is CH2 or S;

[0898] R3 is -NR 11 R11 ' or -C(O)NR 12 R 12 ',in:

[0899] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0900] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0901] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0902] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0903] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0904] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0905] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl(C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0906] or a pharmaceutically acceptable salt of said formula.

[0907] In certain embodiments, the compound is further defined as:

[0908]

[0909] in:

[0910] n is 0, 1, or 2;

[0911] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[0912] Y2 is CH2 or S;

[0913] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0914] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0915] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0916] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0917] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0918] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0919] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0920] or a pharmaceutically acceptable salt of said formula.

[0921] In certain embodiments, the compound is further defined as:

[0922]

[0923] in:

[0924] n is 0, 1, or 2;

[0925] Y2 is CH2 or S;

[0926] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0927] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[0928] R7 and R7' are taken together and are -alkanediyl (C≤7)-, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0929] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0930] or a pharmaceutically acceptable salt of said formula.

[0931] In other embodiments, the compound is further defined as:

[0932]

[0933] in:

[0934] n is 0, 1, or 2;

[0935] Y1 is a substituted -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -;

[0936] Y2 is CH2, O or S;

[0937] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0938] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[0939] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0940] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0941] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0942] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0943] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0944] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0945] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0946] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[0947] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0948] X1 is CR 14 or N, where:

[0949] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[0950] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[0951] X2 is CR 15 or N, where:

[0952] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[0953] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6)or a substituted form of any of these groups; or

[0954] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[0955] or a pharmaceutically acceptable salt of said formula.

[0956] In certain embodiments, the compound is further defined as:

[0957]

[0958] in:

[0959] n is 0, 1, or 2;

[0960] Y1 is a substituted -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -;

[0961] Y2 is CH2, O or S;

[0962] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[0963] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0964] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0965] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[0966] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0967] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0968] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0969] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0970] or a pharmaceutically acceptable salt of said formula.

[0971] In certain embodiments, the compound is further defined as:

[0972]

[0973] in:

[0974] n is 0, 1, or 2;

[0975] Y1 is a substituted -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -;

[0976] Y2 is CH2, O or S;

[0977] R3 is -NR 11 R 11' or -C(O)NR 12 R 12 ',in:

[0978] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[0979] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[0980] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0981] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0982] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0983] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0984] or a pharmaceutically acceptable salt of said formula.

[0985] In certain embodiments, the compound is further defined as:

[0986]

[0987] in:

[0988] n is 0, 1, or 2;

[0989] Y1 is a substituted -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -;

[0990] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[0991] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[0992] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[0993] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[0994] or a pharmaceutically acceptable salt of said formula.

[0995] In other embodiments, the compound is further defined as:

[0996]

[0997] in:

[0998] n is 1 or 2;

[0999] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1000] Y2 is CH2, O or S;

[1001] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1002] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1003] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1004] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1005] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1006] R 12 and R12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1007] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1008] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1009] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1010] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1011] X1 is CR 14 or N, where:

[1012] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[1013] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6), alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[1014] X2 is CR 15 or N, where:

[1015] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[1016] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[1017] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1018] or a pharmaceutically acceptable salt of said formula.

[1019] In certain embodiments, the compound is further defined as:

[1020]

[1021] in:

[1022] n is 1 or 2;

[1023] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1024] Y2 is CH2, O or S;

[1025] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1026] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1027] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1028] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;and

[1029] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1030] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1031] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1032] or a pharmaceutically acceptable salt of said formula.

[1033] In certain embodiments, the compound is further defined as:

[1034]

[1035] in:

[1036] n is 1 or 2;

[1037] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1038] Y2 is CH2, O or S;

[1039] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1040] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1041] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;and

[1042] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1043] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1044] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1045] or a pharmaceutically acceptable salt of said formula.

[1046] In certain embodiments, the compound is further defined as:

[1047]

[1048] in:

[1049] n is 1 or 2; and

[1050] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1051] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1052] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1053] or a pharmaceutically acceptable salt of said formula.

[1054] In other embodiments, the compound is further defined as:

[1055]

[1056] in:

[1057] n is 0, 1, or 2;

[1058] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1059] Y2 is CH2, O or S;

[1060] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8), heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1061] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1062] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1063] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1064] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1065] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1066] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1067] R7 is carboxyl or alkyl (C≤8) , alkenyl(C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1068] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1069] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1070] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1071] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1072] R8 is an alkoxy group (C3-6) , acyloxy (C≤6) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1073] R9 and R 10 are each independently halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12)or a substituted form of any of these groups;

[1074] X1 is CR 14 or N, where:

[1075] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[1076] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[1077] X2 is CR 15 or N, where:

[1078] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[1079] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[1080] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1081] or a pharmaceutically acceptable salt of said formula.

[1082] In certain embodiments, the compound is further defined as:

[1083]

[1084] in:

[1085] n is 0, 1, or 2;

[1086] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1087] Y2 is CH2, O or S;

[1088] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1089] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1090] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1091] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1092] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1093] R 13 is an alkyl group(C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1094] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1095] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1096] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1097] R8 is an alkoxy group (C3-6) , acyloxy (C≤6) , arylalkyloxy (C≤12) or a substituted form of any of these groups; and

[1098] R9 and R 10 are each independently halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1099] or a pharmaceutically acceptable salt of said formula.

[1100] In certain embodiments, the compound is further defined as:

[1101]

[1102] in:

[1103] n is 0, 1, or 2;

[1104] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1105] Y2 is CH2, O or S;

[1106] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1107] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1108] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1109] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1110] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1111] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6)-OR 13 or a substituted form of any of these groups, wherein:

[1112] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1113] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1114] R8 is an alkoxy group (C3-6) , acyloxy (C≤6) , arylalkyloxy (C≤12) or a substituted form of any of these groups; and

[1115] R9 and R 10 are each independently halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1116] or a pharmaceutically acceptable salt of said formula.

[1117] In certain embodiments, the compound is further defined as:

[1118]

[1119] in:

[1120] n is 0, 1, or 2;

[1121] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1122] R 13 is an alkyl group (C≤12), substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1123] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1124] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;or

[1125] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1126] R8 is an alkoxy group (C3-6) , acyloxy (C≤6) , arylalkyloxy (C≤12) or a substituted form of any of these groups; and

[1127] R9 and R 10 are each independently halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1128] or a pharmaceutically acceptable salt of said formula.

[1129] In other embodiments, the compound is further defined as:

[1130]

[1131] in:

[1132] n is 0, 1, or 2;

[1133] Y1 is -alkanediyl(C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1134] Y2 is CH2, O or S;

[1135] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1136] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1137] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1138] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1139] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) ;

[1140] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1141] R4, R5 and R6 are each independently hydrogen, halogen, alkyl(C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1142] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1143] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1144] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1145] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1146] X1 is CR 14 or N, where:

[1147] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[1148] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[1149] X2 is CR 15 or N, where:

[1150] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[1151] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[1152] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1153] or a pharmaceutically acceptable salt of said formula.

[1154] In certain embodiments, the compound is further defined as:

[1155]

[1156] in:

[1157] n is 0, 1, or 2;

[1158] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1159] Y2 is CH2, O or S;

[1160] R3 is -NR 11 R11 ' or -C(O)NR 12 R 12 ',in:

[1161] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) ;

[1162] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1163] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1164] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1165] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1166] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[1167] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl(C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1168] or a pharmaceutically acceptable salt of said formula.

[1169] In certain embodiments, the compound is further defined as:

[1170]

[1171] in:

[1172] n is 0, 1, or 2;

[1173] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1174] Y2 is CH2, O or S;

[1175] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1176] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) ;

[1177] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1178] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1179] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12)or substituted aralkyl (C≤12) ;

[1180] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[1181] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1182] or a pharmaceutically acceptable salt of said formula.

[1183] In certain embodiments, the compound is further defined as:

[1184]

[1185] in:

[1186] n is 0, 1, or 2;

[1187] R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1188] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1189] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[1190] R8, R9 and R 10 are each independently hydrogen, halogen, hydroxyl or alkyl(C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1191] or a pharmaceutically acceptable salt of said formula.

[1192] In other embodiments, the compound is further defined as:

[1193]

[1194] in:

[1195] n is 0, 1, or 2;

[1196] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1197] Y2 is CH2, O or S;

[1198] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1199] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1200] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1201] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1202] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1203] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1204] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1205] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1206] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1207] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl(C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1208] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1209] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups;

[1210] R8 is halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1211] X1 is CR 14 or N, where:

[1212] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[1213] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[1214] X2 is CR 15 or N, where:

[1215] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl(C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[1216] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[1217] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1218] or a pharmaceutically acceptable salt of said formula.

[1219] In certain embodiments, the compound is further defined as:

[1220]

[1221] in:

[1222] n is 0, 1, or 2;

[1223] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1224] Y2 is CH2, O or S;

[1225] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1226] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1227] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1228] R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1229] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1230] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1231] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1232] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1233] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[1234] R8 is halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl(C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1235] or a pharmaceutically acceptable salt of said formula.

[1236] In certain embodiments, the compound is further defined as:

[1237]

[1238] in:

[1239] n is 0, 1, or 2;

[1240] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups;

[1241] Y2 is CH2, O or S;

[1242] R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1243] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1244] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1245] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1246] R13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1247] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1248] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1249] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[1250] R8 is halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1251] or a pharmaceutically acceptable salt of said formula.

[1252] In certain embodiments, the compound is further defined as:

[1253]

[1254] in:

[1255] n is 0, 1, or 2;

[1256] R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic(C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1257] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1258] R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1259] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1260] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[1261] R8 is halogen or hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups;

[1262] or a pharmaceutically acceptable salt of said formula.

[1263] In other embodiments, the compound is further defined as:

[1264]

[1265] in:

[1266] R 16 is an alkyl group (C≤12) , cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or its substituted form;

[1267] R 17 and R 18 are independently hydrogen, alkyl (C≤8) or substituted alkyl (C≤8) ;

[1268] R 19 Is a carboxyl or alkyl group (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1269] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or replaced

[1270] R 19 ' is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1271] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1272] R 20 、R 21 and R 22 are each independently halogen, hydroxy or alkyl(C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups, or a protected hydroxyl group;

[1273] or a pharmaceutically acceptable salt of said formula.

[1274] In certain embodiments, the compound is further defined as:

[1275]

[1276] in:

[1277] R 16 is an alkyl group (C≤12) , cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or its substituted form;

[1278] R 18 Is hydrogen, alkyl (C≤8) or substituted alkyl (C≤8) ;

[1279] R 19 Is a carboxyl or alkyl group (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1280] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or replaced

[1281] R 19 ' is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl(C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1282] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1283] R 20 、R 21 and R 22 are each independently halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups, or a protected hydroxyl group;

[1284] or a pharmaceutically acceptable salt of said formula.

[1285] In certain embodiments, the compound is further defined as:

[1286]

[1287] in:

[1288] R 16 is an alkyl group (C≤12) , cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or its substituted form;

[1289] R 19 is an alkyl group (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) or a substituted form of any of these groups;

[1290] R 20 、R 21 and R 22 Each independently is hydroxyl, alkoxy (C≤12) , substituted alkoxy (C≤12) or protected hydroxyl groups;

[1291] or a pharmaceutically acceptable salt of said formula.

[1292] In certain embodiments, the compound is further defined as:

[1293]

[1294] in:

[1295] R 16 is an alkyl group (C≤12) , cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or its substituted form;

[1296] R 19 Is a carboxyl or alkyl group (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1297] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or replaced

[1298] R 19 ' is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1299] R 13 is an alkyl group (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;

[1300] R20 Is halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups, or a protected hydroxyl group;

[1301] or a pharmaceutically acceptable salt of said formula.

[1302] In certain embodiments, R1 is hydrogen. In certain embodiments, R2 is halogen, such as fluorine. In certain embodiments, X1 is CR 14 In certain embodiments, R 14 In certain embodiments, X2 is CR 15 In certain embodiments, R 15 It's hydrogen.

[1303] In certain embodiments, Y1 is -alkanediyl (C≤6) - or substituted -alkanediyl (C≤6) -. In certain embodiments, Y1 is -alkanediyl (C≤6) -, such as -CH2CH2-. In other embodiments, Y1 is substituted -alkanediyl (C≤6) -, such as -CF2CH2- or -CH(OH)CH2-. In certain embodiments, R3 is -NR 11 R 11 In certain embodiments, R 11 is hydrogen. In other embodiments, R 11 is an alkyl group (C≤6) or substituted alkyl (C≤6) In certain embodiments, R 11 is an alkyl group (C≤6) , such as methyl. In other embodiments, R 11 is acyl (C≤6) or substituted acyl (C≤6) In certain embodiments, R 11 is acyl (C≤6) , such as acetyl. In certain embodiments, R 11 ' is hydrogen. In other embodiments, R 11 ' is an alkyl group (C≤6) or substituted alkyl (C≤6) In certain embodiments, R 11 ' is an alkyl group (C≤6) , such as methyl. In other embodiments, R3 is -C(O)NR 12 R 12In certain embodiments, R 12 is hydrogen. In certain embodiments, R 12 ' is hydrogen.

[1304] In certain embodiments, R4 is hydrogen. In other embodiments, R4 is hydroxy. In certain embodiments, R5 is hydrogen. In other embodiments, R5 is hydroxy. In certain embodiments, R6 is hydrogen. In other embodiments, R6 is hydroxy. In certain embodiments, Y2 is O. In other embodiments, Y2 is S. In other embodiments, Y2 is CH2. In certain embodiments, n is 1 or 2. In other embodiments, n is 0 or 1. In certain embodiments, n is 1. In other embodiments, n is 0.

[1305] In certain embodiments, R9 is hydroxy. In other embodiments, R9 is hydrogen. In certain embodiments, R 10 In other embodiments, R 10 is hydrogen. In other embodiments, R 10 In other embodiments, R 10 It is an acylamino group (C≤12) or substituted acylamino (C≤12) In certain embodiments, R 10 It is an acylamino group (C≤12) , such as -NHC(O)CH3.

[1306] In certain embodiments, R8 is hydroxy. In other embodiments, R8 is alkyl (C≤6) or substituted alkyl (C≤6) In certain embodiments, R8 is alkyl (C≤6) , such as methyl. In other embodiments, R8 is alkoxy (C≤6) or substituted alkoxy (C≤6) In certain embodiments, R8 is alkoxy (C≤6) , such as methoxy or isopropoxy. In other embodiments, R8 is substituted alkoxy (C≤6) , such as difluoromethoxy. In other embodiments, R8 is aralkyloxy (C≤6) or substituted aralkyloxy (C≤6) In certain embodiments, R8 is aralkyloxy (C≤6) , such as benzyloxy.

[1307] In certain embodiments, R7 is hydrogen. In other embodiments, R7 is carboxyl. In other embodiments, R7 is alkyl (C≤6) or substituted alkyl (C≤6) In certain embodiments, R7 is alkyl (C≤6), such as methyl, propyl or isobutyl. In other embodiments, R7 is substituted alkyl (C≤6) , such as hydroxymethyl, fluoromethyl, hydroxyethyl or fluoroisopropyl. In other embodiments, R7 is alkenyl (C≤8) or substituted alkenyl (C≤8) In certain embodiments, R7 is alkenyl (C≤8) , such as allyl. In other embodiments, R7 is aryl (C≤8) or substituted aryl (C≤8) In certain embodiments, R7 is aryl (C≤8) , such as phenyl. In other embodiments, R7 is -alkanediyl (C≤6) -OR 13 In certain embodiments, R 13 is an aralkyl group (C≤8) , such as benzyl.

[1308] In certain embodiments, R7' is hydrogen. In other embodiments, R7' is alkyl (C≤8) or substituted alkyl (C≤8) In certain embodiments, R7′ is alkyl (C≤8) , such as methyl, propyl or isobutyl. In other embodiments, R7′ is alkenyl (C≤8) or substituted alkenyl (C≤8) In certain embodiments, R7′ is alkenyl (C≤8) , such as allyl. In other embodiments, R7′ is aryl (C≤8) or substituted aryl (C≤8) In certain embodiments, R7′ is aryl (C≤8) , such as phenyl. In other embodiments, R7 and R7′ are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups. In certain embodiments, R7 and R7' are taken together and are -CH2CH2CH2CH2- and form a cyclopentyl ring. In other embodiments, R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups. In certain embodiments, R7 and R7' are taken together and are -CH2CH=CHCH2- and form a cyclopentenyl ring.

[1309] In certain embodiments, R 16 is an alkyl group (C≤12) or substituted alkyl (C≤12) In certain embodiments, R 16 is an alkyl group (C≤8) , such as methyl. In certain embodiments, R17 is hydrogen. In certain embodiments, R 18 is an alkyl group (C≤12) or substituted alkyl (C≤12) In certain embodiments, R 18 is an alkyl group (C≤8) , such as methyl. In certain embodiments, R 19 is an alkyl group (C≤12) or substituted alkyl (C≤12) In certain embodiments, R 19 is an alkyl group (C≤8) , such as methyl. In certain embodiments, R 19 ' is hydrogen.

[1310] In certain embodiments, R 20 In other embodiments, R 20 Alkoxy (C≤12) or substituted alkoxy (C≤12) In certain embodiments, R 20 Alkoxy (C≤8) , such as methoxy. In certain embodiments, R 21 In certain embodiments, R 22 It is a hydroxyl group.

[1311] In certain embodiments, the compound is further defined as:

[1312]

[1313]

[1314]

[1315]

[1316]

[1317]

[1318] Or a pharmaceutically acceptable salt of any one of these formulas. In yet another aspect, the present disclosure provides a compound of the formula:

[1319] Or a pharmaceutically acceptable salt of any one of these formulas. In another aspect, the present disclosure provides a compound of the formula:

[1320]

[1321] wherein said compound is substantially free of any other stereoisomers;

[1322] or a pharmaceutically acceptable salt of said formula.

[1323] In yet another aspect, the present disclosure provides compounds of the formula:

[1324]

[1325] wherein said compound is substantially free of any other stereoisomers;

[1326] or a pharmaceutically acceptable salt of said formula.

[1327] In yet another aspect, the present disclosure provides a compound of the formula:

[1328]

[1329] wherein the compound is greater than 90% deuterated at the positions shown in the formula.

[1330] In another aspect, the present disclosure provides a pharmaceutical composition comprising:

[1331] (A) a compound described herein; and

[1332] (B) Excipients.

[1333] In certain embodiments, the pharmaceutical composition is formulated for oral administration, intraadipose, intraarterial, intraarticular, intracranial, intradermal, intralesional, intramuscular, intranasal, intraocular, intrapericardial, intraperitoneal, intrapleural, intraprostatic, intrarectal, intrathecal, intratracheal, intratumoral, intraumbilical, intravaginal, intravenous, intravesical, intravitreal, in liposome form, locally, mucosally, parenterally, rectally, subconjunctival, subcutaneously, sublingually, topically, buccally, transdermally, vaginally, in the form of creams, in the form of lipid compositions, via catheter, via lavage, via continuous infusion, via infusion, via inhalation, via injection, via local delivery, or via local perfusion. In certain embodiments, the pharmaceutical composition is formulated for oral, intraarterial, or intravenous administration. In certain embodiments, the pharmaceutical composition is formulated as a unit dose.

[1334] In yet another aspect, the present disclosure provides a method for treating a disease or disorder in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or composition described herein. In certain embodiments, the disease or disorder is a neurological disorder. In other embodiments, the disease or disorder is diabetes or its complications. In certain embodiments, the disease or disorder is a complication caused by diabetes, such as neuropathy, nephropathy, retinopathy, or vasculopathy. In certain embodiments, the complication caused by diabetes is neuropathy, such as diabetic peripheral neuropathy. In certain embodiments, the disease or disorder is associated with misregulation of Hsp70 proteins. In certain embodiments, the disease or disorder is associated with misregulation of Hsp90 proteins. In certain embodiments, the patient is a mammal, such as a human. In certain embodiments, the compound is administered to the patient once. In other embodiments, the compound is administered to the patient twice or more.

[1335] In another aspect, the present disclosure provides a method for inducing the expression of an Hsp70 protein, comprising contacting the protein with an effective amount of a compound or composition described herein that is sufficient to induce the expression of the Hsp70 protein. In certain embodiments, the protein is contacted in vitro. In other embodiments, the protein is contacted in vivo. In certain embodiments, an effective amount of the compound or composition is sufficient to effectively induce the expression of at least 50% (such as more than 100%) of the Hsp70 protein. In certain embodiments, the induction of Hsp70 protein expression is sufficient to treat a disease or disorder. In certain embodiments, the disease or disorder is a neurodegenerative disease, such as a neurodegenerative disease associated with misfolded proteins, demyelination, inflammation, and neuropathy. In certain embodiments, the neurodegenerative disease is diabetic peripheral neuropathy. In other embodiments, the disease or disorder is cancer. In other embodiments, the induction of Hsp70 protein expression results in the regulation of the expression of one or more downstream products. In certain embodiments, the induction of Hsp70 protein expression results in the regulation of the activity of one or more downstream products.

[1336] In yet another aspect, the present disclosure provides methods for inhibiting an Hsp90 protein, comprising contacting the protein with an effective amount of a compound or composition described herein sufficient to inhibit the activity of the Hsp90 protein. In certain embodiments, the protein is contacted in vitro. In other embodiments, the protein is contacted in vivo. In certain embodiments, the effective amount of the compound or composition is sufficient to effectively inhibit the expression of the Hsp90 protein by at least 50%, such as when Hsp90 protein expression is inhibited by greater than 75%. In certain embodiments, inhibition of Hsp90 protein expression is sufficient to treat a disease or disorder. In certain embodiments, the disease or disorder is cancer or a hyperproliferative disorder. In certain embodiments, the disease or disorder is associated with hyperproliferative cells. In certain embodiments, inhibition of Hsp90 protein expression results in modulation of the expression of one or more downstream products. In other embodiments, inhibition of Hsp90 protein expression results in modulation of the activity of one or more downstream products.

[1337] In yet another aspect, the present disclosure provides compounds of the formula:

[1338]

[1339] in:

[1340] n is 0, 1, or 2;

[1341] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) -, -alkanediyl (C≤6) -C(O)R 17 or a substituted form of any of these groups, wherein:

[1342] R 17 is an alkyl group (C≤6) or substituted alkyl (C≤6) ;

[1343] Y2 is a hydroxyl group or a thiol group;

[1344] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1345] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6), alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1346] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1347] R3 is carboxyl, -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in:

[1348] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1349] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1350] R4, R5 and R6 are each independently absent, hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , arylalkyloxy (C≤12) , substituted aralkyloxy (C≤12) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1351] X1 is CR 14 or N, where:

[1352] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino(C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[1353] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and

[1354] X2 is CR 15 or N, where:

[1355] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[1356] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[1357] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1358] Provided that the compound is not a compound of the formula:

[1359]

[1360] In certain embodiments, the compound is further defined as:

[1361]

[1362] In another aspect, the present disclosure provides a method of preparing a compound described herein, comprising reacting (a) with (b) in the presence of a coupling agent:

[1363] (a) a compound of the formula:

[1364]

[1365] in:

[1366] n is 0, 1, or 2;

[1367] Y1 is -alkanediyl (C≤6) -, -C(O)-alkanediyl (C≤6) -, -alkanediyl (C≤6) -C(O)R 17 or a substituted form of any of these groups, wherein:

[1368] R 17 is an alkyl group (C≤6) or substituted alkyl (C≤6) ;

[1369] Y2 is a hydroxyl group or a thiol group;

[1370] R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1371] R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups;

[1372] R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1373] R3 is carboxyl, -NR 11 R 11 ' or -C(O)NR 12 R12 ',in:

[1374] R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ;

[1375] R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ;

[1376] R4, R5 and R6 are each independently absent, hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , arylalkyloxy (C≤12) , substituted aralkyloxy (C≤12) , acyloxy (C≤6) or substituted acyloxy (C≤6) ;

[1377] X1 is CR 14 or N, where:

[1378] R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or

[1379] R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1380] X2 is CR 15 or N, where:

[1381] R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6), alkylamino (C≤6) ,-alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups;

[1382] R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or

[1383] R 15 Together with R2, it is an alkanediyl group (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups;

[1384] (b) a compound of the formula:

[1385]

[1386] in:

[1387] n is 0, 1, or 2;

[1388] Y3 is hydroxy, halogen, acyloxy (C≤8) , iminooxy (C≤8) or a substituted form of any of these groups;

[1389] R7 and R7' are each independently hydrogen, hydroxy, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) ,-alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein:

[1390] R 13 is an aralkyl group (C≤12) or substituted aralkyl (C≤12) ;

[1391] R7 and R7' are taken together and are -alkanediyl (C≤7) -, -alkene diyl (C≤7) - or a substituted form of any of these groups; and

[1392] R8, R9 and R 10 are each independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , arylalkyloxy (C≤12) or a substituted form of any of these groups.

[1393] In certain embodiments, the coupling agent is a Lewis acid. In certain embodiments, the Lewis acid comprises a boron reagent, such as BF3, or more specifically BF3.Et2O. In certain embodiments, the method further comprises a solvent. In other embodiments, the method does not comprise a solvent.

[1394] Other objects, features, and advantages of the present disclosure will become apparent from the detailed description that follows. However, it should be understood that the detailed description and specific examples, while indicating specific embodiments of the present invention, are given by way of example only, as various changes and modifications within the spirit and scope of the present invention will become apparent to those skilled in the art from this detailed description. It should be noted that just because a particular compound is assigned to a particular general formula does not mean that it may not also belong to another general formula. BRIEF DESCRIPTION OF THE DRAWINGS

[1395] The following drawings form part of this specification and are included to further demonstrate certain aspects of the present disclosure. The invention may be better understood by reference to one of these drawings in conjunction with the detailed description of specific embodiments presented herein.

[1396] Figures 1A to 1C Compound T0 (KU-596) ( Figure 1A )、T2( Figure 1B ) and T1( Figure 1C ) Results of a streptozotocin-induced rat diabetes model of painful diabetic neuropathy. After collecting baseline von Frey measurements of allodynia, streptozotocin was injected into the rats to induce diabetes. After another von Frey measurement, oral administration of each test drug was started. Both compounds T1 and T2 showed comparable to slightly better activity than compound T0 (KU-596).

[1397] Figure 2 Shown are von Frey measurements of compounds T10 and T54 in a streptozotocin-induced rat diabetic model of painful diabetic neuropathy. DETAILED DESCRIPTION

[1398] In certain aspects, the present disclosure provides biarylamide compounds having modified sugar groups that are useful for treating and preventing diseases and disorders, including neurological disorders, such as neurodegenerative diseases and nerve-damaging disorders, for example, diabetic peripheral neuropathy.

[1399] I. Compounds of the Present Invention

[1400] The compounds of the present invention (also referred to as "compounds of the present disclosure" or "compounds disclosed herein") are shown in the formulae provided, for example, in the Summary of the Invention section above, the above paragraphs, the claims below, and Table 1 below. They can be prepared using the synthetic methods outlined in the Examples section. These methods can be further modified and optimized using the principles and techniques of organic chemistry as applied by those skilled in the art. Such principles and techniques are taught in, for example, Smith, March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (March Advanced Organic Chemistry - Reactions, Mechanisms and Structure), (2013), which is incorporated herein by reference. In addition, the synthetic methods can be further modified and optimized using the principles and techniques of process chemistry as applied by those skilled in the art for batch or continuous preparation, pilot- or large-scale production. Such principles and techniques are taught in, for example, Anderson, Practical Process Research & Development - A Guide for Organic Chemists (2012), which is incorporated herein by reference.

[1401] Table 1: Examples of biaryl and coumarin-based compounds with modified sugar groups

[1402]

[1403]

[1404]

[1405]

[1406]

[1407]

[1408]

[1409]

[1410]

[1411]

[1412]

[1413]

[1414] In certain embodiments, the listed compounds can be used for preventing and treating one or more diseases or disorders discussed herein or elsewhere. In certain embodiments, compounds based on biaryls and coumarins with modified sugar derivatives covered by the claims or otherwise disclosed herein can be used. All such compounds are considered to be "active compounds" and "therapeutic compounds" intended to be used as active pharmaceutical ingredients (APIs). Conventionally, a combination of clinical trial protocols and prescribed procedures (such as those promulgated by the Food and Drug Administration (FDA)) is used to determine the actual suitability for human or veterinary applications. In the U.S., FDA is responsible for protecting public health by ensuring the safety, effectiveness, quality and reliability of human and veterinary drugs, vaccines and other biological products and medical devices.

[1415] Also disclosed herein are compounds that are synthetic intermediates useful in the preparation and manufacture of the disclosed and claimed biaryl and coumarin-based compounds having modified sugar groups. Such synthetic intermediates are disclosed throughout the application, including, for example, in the synthetic schemes presented in the Examples section below.

[1416] In certain embodiments, the compounds of the present invention have the advantage that, whether used for the indications described herein or otherwise, they may be more effective, less toxic, longer acting, more potent, produce fewer side effects, be more readily absorbed, more stable, more metabolically stable, more lipophilic, more hydrophilic, and / or have better pharmacokinetic properties (e.g., higher oral bioavailability and / or lower clearance), and / or have other useful pharmacological, physical or chemical properties compared to compounds known in the prior art.

[1417] The compounds of the present invention may contain one or more asymmetrically substituted carbon or nitrogen atoms and may be separated in optically active or racemic forms. Therefore, unless otherwise specified, all chiral, diastereoisomer, racemic, epimeric and all geometric isomeric forms of the chemical formula are intended. The compounds may exist as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. In certain embodiments, a single diastereomer is obtained. The chiral center of the compounds of the present invention may have an S or R configuration.

[1418] Chemical formulae used to represent compounds of the present invention generally depict only one of several possible tautomers. For example, many types of keto groups are known to exist in equilibrium with corresponding enol groups. Similarly, many types of imine groups exist in equilibrium with enamine groups. Regardless of which tautomer is depicted for a given compound, and regardless of which is most prevalent, all tautomers of a given formula are intended.

[1419] In addition, the atoms comprising the compounds of the present invention are intended to include all isotopic forms of these atoms. As used herein, isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and not limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include 13 C and 14 C.

[1420] In certain embodiments, the compound of the present invention works as a prodrug, or can be derivatized to work as a prodrug. Because known prodrugs can enhance the numerous desirable properties (e.g., solubility, bioavailability, manufacturing, etc.) of a drug, the compound used in some methods of the present invention can be delivered in a prodrug form if desired. Thus, the present invention contemplates the prodrug of the compound of the present invention and the method for delivering the prodrug. The prodrug of the compound used in the present invention can be prepared by modifying the functional group present in the compound in the following manner: the modification is cleaved in conventional operation or in vivo to form a parent compound. Therefore, prodrugs include compounds such as described herein, wherein hydroxyl, amino or carboxyl are bonded to any group, and when the prodrug is administered to a patient, any group cleavage forms a hydroxyl, amino or carboxylic acid.

[1421] In certain embodiments, the compounds of the present invention exist in salt or non-salt form. With regard to salt forms, in certain embodiments, the specific anion or cation forming part of any salt form of the compounds provided herein is not critical, as long as the salt as a whole is pharmacologically acceptable. Other examples of pharmaceutically acceptable salts and their preparation methods and methods of use are presented in Handbook of Pharmaceutical Salts: Properties, and Use (2002), which is incorporated herein by reference.

[1422] It should be understood that many organic compounds can form complexes with the solvents in which they are reacted or precipitated or crystallized. These complexes are referred to as "solvates." Where the solvent is water, the complex is referred to as a "hydrate." It should also be understood that many organic compounds can exist in more than one solid form, including crystalline and amorphous forms. All solid forms of the compounds provided herein, including any solvates thereof, are within the scope of the present invention.

[1423] II. Indications

[1424] Approximately 26 million Americans have type 1 or type 2 diabetes. Despite using insulin and oral antidiabetic medications to help maintain normal blood sugar levels, approximately 60-70% of these individuals develop diabetic peripheral neuropathy (DPN) (Veves et al., 2008).

[1425] Diabetic peripheral neuropathy may first manifest as a neuropathic pain syndrome, in which the patient experiences significant pain in the absence of a painful stimulus (allodynia), or has an exaggerated sense of pain (hyperalgesia) in response to stimuli that would normally be considered only mildly noxious. Hyperalgesia can be thermal (in response to moderate temperature changes, whether hot or cold) or mechanical (in response to pressure or some other physical stimulus). Furthermore, a given patient may experience allodynia and hyperalgesia at different times.

[1426] Some patients with painful diabetic neuropathy go on to develop insensate neuropathy, in which the patient has an impaired ability to sense pressure, temperature changes, or even severe injury in the affected area. Insensate neuropathy is most commonly found in the limbs, particularly the distal limbs, with a classic "stocking and glove" distribution. It is an important contributor to overall morbidity, as diabetic patients often suffer from poor wound healing, and the inability to sense injury can severely impair response and treatment. Some patients do not develop painful diabetic neuropathy, but instead present with insensate neuropathy first. Other patients may experience numbness and hypersensitivity. Certain classifications of diabetic sensory polyneuropathy (DPN) identify typical and atypical forms of the condition. The most common form, diabetic sensorimotor polyneuropathy (DSPN), is associated with long-term hyperglycemia and microvascular changes, and is statistically associated with retinopathy and nephropathy. Atypical DPN differs from DSPN in onset, course, manifestations, and possible mechanisms (Tesfaye et al., 2010; Callaghan et al., 2012).

[1427] A number of small molecules based on the novobiocin scaffold have been reported to inhibit heat shock protein 90 (Hsp90) and have significant neuroprotective properties, including reversal of DPN symptoms in animal models.

[1428] One of this class of novobiocin analogs (“novologues”) is KU-32, the first novobiocin analog to be shown to have significant activity in reversing established DPN symptoms in diabetic mice (Ma et al., 2014). Another novobiocin analog is N-(2-(5-(((3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetra-hydro-2H-pyran-2-yl)oxy)-3'-fluoro-[1,1'-biphenyl]-2-yl)ethyl)-acetamide, also known as KU-596, which has also been reported to protect neurons from hyperglycemia in vitro and reduce symptoms of neuropathy in diabetic mice (Kusuma et al., 2012; U.S. Patent No. 9,422,230; Ma et al., 2015). Because diabetic neuropathy shares many features with other causes of neuropathies (such as neuropathic pain induced by physical trauma or ischemia, or drug-induced neuropathy), compounds that inhibit Hsp90 and are able to reverse the symptoms of DPN, such as the compounds described herein, may also be used to treat neuropathy more generally. Neuropathic pain of non-diabetic origin is an area of ​​urgent need, as many patients do not respond to existing therapies or only achieve partial relief of their symptoms.

[1429] In addition to its effect in the diabetic neuropathy model, it has been reported that KU-596 also improves impaired mitochondrial function in neurons and reduces the expression of inflammatory markers in diabetic neurons (Ma et al. 2015). Because diabetic tissue undergoes significant oxidative stress, these results indicate that the compound and mechanistically related compounds (such as KU-32) can be used to treat other neurological disorders involving oxidative stress and chronic inflammation, including neurodegenerative diseases, epilepsy, multiple sclerosis, spinal cord injury, demyelinating neurological disorders and psychiatric disorders, including schizophrenia, depression, bipolar disorder, autism and related disorders, and post-traumatic stress disorder. More generally, compounds that exhibit similar mechanistic effects, such as the compounds of the present invention, have potential uses in non-neurological diseases (including osteoarthritis, autoimmune diseases and mitochondrial myopathy) involving mitochondrial dysfunction or chronic or acute oxidative stress and inflammation. These compounds can also be used in combination with other therapies, particularly therapies that reduce oxidative stress, inflammation and mitochondrial dysfunction by other mechanisms.

[1430] A. Hsp70 protein

[1431] In certain embodiments, the compounds and compositions provided herein can be used to regulate the expression and / or activity of Hsp70 proteins, or to regulate the activity of targets or signaling pathways regulated by Hsp70. Hsp70 proteins act as chaperones that assist in protein folding and have a variety of different biological functions in normal cells. Specifically, Hsp70 is involved in protein folding and transport of proteins into organelles, identification of damaged proteins, and assisting in marking these proteins for destruction. It also recognizes proteins containing specific amino acid sequences and transports these proteins to specific organelles such as lysosomes. It is worth noting that Hsp70 is an important regulatory factor for protein import into mitochondria. Without wishing to be bound by any theory, it is believed that up to 30% of proteins interact with Hsp70 to ensure their proper folding, and Hsp70 interacts with the hydrophobic portion of proteins to prevent them from degradation. In addition, Hsp70 also helps identify proteins that have been irreversibly damaged and transports these proteins to the proteasome for degradation. Such degradation occurs in conjunction with Bag-1 and CHIP proteins.

[1432] In addition, Hsp70 proteins have been implicated in identifying and labeling proteins for degradation under fasting or other nutrient-deficient conditions. Specifically, the presence of the amino acid sequence KFPRQ within a protein is known to trigger lysosomal degradation of the protein under such conditions.

[1433] The effects of novobiocin analogs in a model of diabetic neuropathy have been shown to be Hsp70-dependent, as Hsp70 knockout mice were unresponsive to these compounds at doses that were fully effective in wild-type mice.

[1434] B. Hsp90 protein

[1435] In certain embodiments, the compounds and compositions of the present disclosure can bind to the C-terminus of the Hsp90 protein and thereby prevent natural substrates from binding to the protein. Using molecular modeling techniques and data derived from preliminary observations of neomycin binding to the C-terminus, other neomycin analogs, particularly KU-32 and KU-596, have been designed to bind to the C-terminus of Hsp90 (e.g., Kusuma et al., 2012). Hsp90 is a molecular chaperone protein that, in addition to assisting protein folding, protein degradation, and alleviating heat stress, is also involved in stabilizing a variety of cancer-related proteins. It has been shown that inhibition of the Hsp90 protein can lead to apoptosis in cancer cells. Without being bound by theory, many different molecular pathways are involved in the role of the Hsp90 protein in cancer development and spread. For example, this protein is involved in stabilizing mutant oncogenic proteins such as v-Src, Bcr / Abl, and p53, stabilizing several growth factors and signaling molecules such as EGFR, PI3K, and AKT proteins, which promotes growth factor signaling pathways and promotes the induction of VEGF, nitric oxide synthase, and matrix metalloproteinase MMP2 (which promote angiogenesis and cancer cell metastasis). Many different cancer types and subtypes rely on pathways mediated by Hsp90 proteins for proliferation and tumor development, and inhibitors of the highly conserved Hsp90 protein are considered to have the potential to treat a variety of cancers.

[1436] C. Neurological diseases or disorders

[1437] In another aspect, provided herein are compounds, compositions and methods that can be used to treat neurological diseases and disorders, including those that affect the central nervous system, and those that affect the peripheral nervous system. In certain embodiments, provided herein are compounds, compositions and methods that can be used to treat neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, which are believed to be caused primarily by neurodegenerative lesions in the central nervous system. In certain embodiments, provided herein are compounds, compositions and methods that can be used to treat other neurological diseases and disorders involving central or peripheral neurodegenerative lesions or neuronal damage, such as epilepsy, psychiatric disorders and peripheral neuropathy. Without being bound by any theory, in certain embodiments, compounds and compositions of the present disclosure provide neuroprotective effects by regulating the activity of Hsp90, and therefore can be used to inhibit progressive degeneration of neurons, wherein progressive degeneration of neurons can lead to cell death.

[1438] Examples of neurological disorders or diseases that can be treated with the compounds, compositions and methods disclosed herein include, but are not limited to, chronic neurological diseases such as diabetic peripheral neuropathy (including third nerve palsy, mononeuropathy, multiple mononeuropathy, diabetic amyotrophy, autonomic neuropathy and thoracoabdominal neuropathy), Alzheimer's disease, age-related memory loss, senility, age-related dementia, Pick's disease, diffuse Lewy body disease, progressive supranuclear palsy (Steel-Richardson syndrome), multiple system degeneration (Shy-Drager syndrome), ) syndrome), motor neuron diseases including amyotrophic lateral sclerosis ("ALS"), degenerative ataxias, corticobasal degeneration, ALS-Parkinson's disease-dementia complex of Guam type, subacute sclerosing panencephalitis, Huntington's disease, Parkinson's disease, multiple sclerosis ("MS"), synucleinopathies, primary progressive aphasia, striatonigral degeneration, Machado-Joseph disease / spinocerebellar ataxia type 3 and olivopontocerebellar degeneration, spinocerebellar ataxias (including types 1, 2, 3, and 12), Gilles de la Tourette's disease, and schizophrenia. De La Tourette disease, bulbar and pseudobulbar palsy, spinal and spinobulbar muscular atrophy (Kennedy disease), primary lateral sclerosis, familial spastic paraplegia, Wernicke-Korsakoff-related dementia (alcohol-induced dementia), Werdnig-Hoffmann disease, Kugelberg-Welander disease, Tay-Sach disease, Sandhoff disease, familial spastic disorders, Wohifart-Kugelberg-Welander disease, Charcot-Marie-Tooth disease, Charlevoix-Saguenay autosomal recessive spastic ataxia, dentatorubral-pallidoluysian atrophy atrophy), cystic fibrosis neuropathy, frontotemporal dementia and Parkinson's disease linked to chromosome 17, familial amyloid polyneuropathy, trigeminal neuralgia associated with multiple sclerosis, spastic paraparesis, progressive multifocal leukoencephalopathy, and prion diseases (including Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, kuru, and fatal familial insomnia).Other conditions also included in the methods of the present invention include age-related dementia and other dementias, as well as conditions associated with memory loss, including vascular dementia, diffuse white matter disease (Binswanger's disease), dementia of endocrine or metabolic origin, dementia caused by head trauma and diffuse brain injury, pugilistic dementia, and frontal lobe dementia. Degenerative diseases of the retina and optic nerve are also included in the methods of the present invention, including retinitis pigmentosa, optic neuritis, dominant optic atrophy, Leber's hereditary optic neuropathy, and glaucoma. As well as other neurodegenerative disorders caused by cerebral ischemia or infarction, including embolic and thrombotic occlusions, and intracranial hemorrhage of any type (including, but not limited to, epidural, subdural, subarachnoid, and intracerebral), as well as intracranial and intraspinal lesions (including, but not limited to, contusions, penetrations, shearing, crushing, and avulsions). Thus, the above terms also encompass acute neurodegenerative disorders, such as those involving stroke, traumatic brain injury, schizophrenia, peripheral nerve injury, hypoglycemia, spinal cord injury, epilepsy, as well as anoxia and hypoxia.

[1439] In certain embodiments, the neurodegenerative disorder is amyloidosis. Amyloidosis is observed in Alzheimer's disease, hereditary cerebrovascular disease, non-neuropathic hereditary amyloid, Down syndrome, macroglobulinemia, secondary familial Mediterranean fever, Muckle-Wells syndrome, multiple myeloma, pancreatic and cardiac related amyloidosis, chronic hemodialysis arthropathy, and Finnish and Iowa amyloidosis. In a preferred embodiment, the neurodegenerative disorder treated and / or prevented using the methods and compositions of the present disclosure is diabetic peripheral neuropathy.

[1440] D. Diseases related to mitochondrial dysfunction

[1441] Among its other functions, Hsp70 plays an important role in regulating the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix and promoting their proper processing and folding after import (Harbauer et al., 2014). KU-32, a compound mechanistically related to the compounds of the present invention, has been shown to improve mitochondrial bioenergetics (Ma et al., 2014). Another novobiocin analog, KU-596, has been reported to improve impaired mitochondrial function in neurons and reduce the expression of inflammatory markers in diabetic neurons (Ma et al., 2015). Thus, in certain embodiments, the compounds, compositions, and methods provided herein can be used to prevent or treat diseases or disorders involving mitochondrial dysfunction. Non-limiting examples of these include: various neurological disorders (including neurodegenerative diseases, epilepsy), psychiatric disorders (including depression, schizophrenia, anxiety disorders, PTSD and bipolar disorder), neurodevelopmental disorders (including autism and attention deficit disorder), neuromuscular disorders (including Friedreich's ataxia, mitochondrial myopathies, muscular dystrophy and various forms of dystonia), chronic progressive lateral ophthalmoplegia, muscle wasting diseases (including age-related muscle wasting, diabetes-related muscle wasting, cancer-related cachexia, dialysis-related cachexia, anorexia-related cachexia and myasthenia gravis), impaired myocardial function associated with heart failure and other forms of cardiovascular disease, retinal disorders, obesity, diabetes, and diabetic complications.

[1442] III. Pharmaceutical Formulations and Administration Routes

[1443] In another aspect, in order to administer to the patient who needs such treatment, pharmaceutical preparations (also referred to as pharmaceutical products, pharmaceutical compositions, pharmaceutical products, medical products, medicines, drugs or medicaments) include a therapeutically effective amount of a compound disclosed herein, which is formulated together with one or more excipients and / or pharmaceutical carriers suitable for the indicated route of administration. In certain embodiments, the compound disclosed herein is formulated in a manner suitable for treating humans and / or veterinary patients. In certain embodiments, formulation includes mixing or combining one or more compounds disclosed herein with one or more of the following excipients: lactose, sucrose, starch powder, cellulose esters of alkanoic acid, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric acid and sulfuric acid, gelatin, gum arabic, sodium alginate, polyvinyl pyrrolidone and / or polyvinyl alcohol. In certain embodiments, for example, for oral administration, the pharmaceutical preparation can be made into tablets or loaded into capsules. In certain embodiments, the compound can be dissolved in or slurried in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and / or various buffers. In certain embodiments, the pharmaceutical preparations can be subjected to pharmaceutical manipulations, such as sterilization, and / or can contain pharmaceutical carriers and / or excipients such as preservatives, stabilizers, wetting agents, emulsifiers, encapsulating agents such as lipids, dendrimers, polymers, proteins such as albumin, nucleic acids, and buffers.

[1444] Pharmaceutical preparations can be administered by a variety of methods, such as orally or by injection (e.g., subcutaneously, intravenously, and intraperitoneally). Depending on the route of administration, the compounds disclosed herein can be encapsulated in materials to protect the compound from the effects of acid and other natural conditions that may inactivate the compound. In order to administer the active compound in a manner other than parenteral administration, it may be necessary to coat the compound with a substance that prevents its inactivation, or to co-administer it with the compound. In certain embodiments, the active compound can be administered to the patient in an appropriate carrier (e.g., liposomes or diluents). Pharmaceutically acceptable diluents include saline and buffered aqueous solutions. Liposomes include water-in-oil-in-water CGF emulsions and conventional liposomes.

[1445] The compounds disclosed herein can also be administered parenterally, intraperitoneally, intrathecally or intracerebrally. Dispersions can be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof, as well as in oils. Under ordinary storage and use conditions, these preparations may contain preservatives to prevent the growth of microorganisms.

[1446] The pharmaceutical composition that is suitable for injection includes sterile aqueous solution (when water-soluble) or dispersion, and the sterile powder for instant preparation of sterile injectable solution or dispersion.Described carrier can be solvent or dispersion medium, and it contains for example water, ethanol, polyol (for example, glycerol, propylene glycol and liquid polyethylene glycol etc.), its suitable mixture, and vegetable oil.Suitable fluidity can be for example by using coating agent such as lecithin, by maintaining required particle size (when dispersion) and by using surfactant to maintain.The stopping of microbial action can be realized by various antibacterial and antifungal agents, for example, parahydroxybenzoate, chlorobutanol, phenol, ascorbic acid, thimerosal etc. In many cases, preferably include isotonic agent in described composition, for example, sugar, sodium chloride or polyol such as mannitol and sorbitol.By including the reagent (for example, aluminum monostearate or gelatin) that delays absorption in composition, the extended absorption of injectable composition can be realized.

[1447] The compounds disclosed herein can be taken orally, for example, with an inert diluent or an assimilable edible carrier. The compound and other ingredients can also be encapsulated in a hard or soft shell gelatin capsule, compressed into tablets, or directly incorporated into the patient's diet. For oral therapeutic administration, the compounds disclosed herein can be combined with excipients and used in the form of ingestible tablets, buccal tablets, lozenges, capsules, elixirs, suspensions, syrups, film tablets (wafers), etc. The percentage of the therapeutic compound in the composition and preparation can certainly vary. The amount of the therapeutic compound in such a pharmaceutical preparation is such that a suitable dosage will be obtained.

[1448] The therapeutic compound can also be applied topically to the skin, eyes, ears, or mucous membranes. Topical application of the therapeutic compound can include formulations of the compound as topical solutions, lotions, creams, ointments, gels, foams, transdermal patches, or tinctures. When the therapeutic compound is formulated for topical application, the compound can be combined with one or more agents that increase the permeability of the compound through the tissue to which it is applied. In other embodiments, it is contemplated that topical application is to the eye. Such application can be applied to the surface of the cornea, conjunctiva, or sclera. Without wishing to be bound by any theory, it is believed that application to the surface of the eye allows the therapeutic compound to reach the back of the eye. Topical ocular application can be formulated as a solution, suspension, ointment, gel, or emulsion. Finally, topical application can also include application to mucous membranes such as the inside of the mouth. Such application can be applied directly to specific locations within the mucous membrane, such as teeth, sores, or ulcers. Alternatively, if local delivery to the lungs is desired, the therapeutic compound can be administered by inhalation in the form of a dry powder or aerosol formulation.

[1449] In certain embodiments, for ease of administration and uniformity of dosage, it may be advantageous to formulate the parenteral composition in dosage unit form. As used herein, dosage unit form refers to physically discrete units suitable as unit doses for the patient to be treated; each unit contains a predetermined amount of the therapeutic compound calculated to produce the desired therapeutic effect, in combination with a desired pharmaceutical carrier. In certain embodiments, the specifications of the dosage unit forms of the present invention are determined by and directly depend on: (a) the unique characteristics of the therapeutic compound and the specific therapeutic effect to be achieved, and (b) the limitations inherent in the art of formulating such therapeutic compounds for the treatment of the selected condition of the patient. In certain embodiments, the active compound is administered in a therapeutically effective dose sufficient to treat a condition associated with the patient's condition. For example, the efficacy of the compound can be evaluated in an animal model system that can predict the efficacy of treating a disease in a human or another animal.

[1450] In certain embodiments, the effective dose range of a therapeutic compound can be extrapolated from the effective doses determined in animal studies of a variety of different species. In certain embodiments, the human equivalent dose (HED) in mg / kg can be calculated according to the following formula (see, e.g., Reagan-Shaw et al., FASEB J., 22(3):659-661, 2008, which is incorporated herein by reference):

[1451] HED (mg / kg) = animal dose (mg / kg) × (animal K m / personK m )

[1452] Apply K in the transformation m The factor will produce HED values ​​based on body surface area (BSA) rather than just body weight. m The values ​​are well known. For example, the average 60 kg person (BSA is 1.6 m 2 ) of K m is 37, while a 20 kg child (BSA is 0.8 m 2 ) has a K of 25 m K in some related animal models m Also well known, including: mouse K m is 3 (given a weight of 0.02 kg and a BSA of 0.007); the K m is 5 (given a weight of 0.08 kg and a BSA of 0.02); the K m is 6 (given a weight of 0.15 kg and a BSA of 0.025), the K m is 12 (given a weight of 3 kg and a BSA of 0.24).

[1453] The exact amount of the therapeutic composition depends on the judgment of the practitioner and is specific to each individual. Nevertheless, the calculated HED dosage can provide general guidance. Other factors affecting dosage include the patient's physical and clinical state, the route of administration, the intended therapeutic goal, and the efficacy, stability, and toxicity of the specific therapeutic formulation.

[1454] The amount of the actual dose of the compound of the present invention or the composition comprising the compound of the present invention administered to the patient can depend on physical and physiological factors, such as the type of animal being treated, age, sex, weight, severity of the condition, type of disease being treated, previous or concurrent therapeutic interventions, idiopathic conditions of the patient, and route of administration. These factors can be determined by a skilled person. The practitioner responsible for administration will typically determine the concentration of the active ingredient in the composition and the appropriate dose for the individual patient. In the event of any complications, the dosage can be adjusted by the physician personally.

[1455] In certain embodiments, the therapeutically effective amount is typically between about 0.001 mg / kg to about 1000 mg / kg, about 0.01 mg / kg to about 750 mg / kg, about 100 mg / kg to about 500 mg / kg, about 1 mg / kg to about 250 mg / kg, about 10 mg / kg to about 150 mg / kg, administered in one or more doses per day for one or more days (depending, of course, on the mode of administration and the factors discussed above). Other suitable dosage ranges include 1 mg to 10,000 mg / day, 100 mg to 10,000 mg / day, 500 mg to 10,000 mg / day, and 500 mg to 1,000 mg / day. In certain embodiments, the amount is less than 10,000 mg / day, with a range of 750 mg to 9,000 mg / day.

[1456] In certain embodiments, the amount of active compound in the pharmaceutical formulation is from about 2 to about 75% by weight. In certain of these embodiments, the amount is from about 25 to about 60% by weight.

[1457] Single or multiple doses of the agent are contemplated. The desired time interval for multiple dose delivery can be determined by one of ordinary skill in the art using no more than routine experimentation. As an example, two doses can be administered to the patient daily at intervals of approximately 12 hours. In certain embodiments, the agent is administered once daily.

[1458] The medicament can be used according to the conventional schedule. The conventional schedule used herein represents a predetermined specified time period. The conventional schedule can cover the same time period, or the time period of different lengths, as long as the schedule is predetermined. For example, the conventional schedule can include using 2 times a day, 1 time a day, 1 time per two days, 1 time per three days, 1 time per four days, 1 time per five days, 1 time per six days, 1 time per week, 1 time per month, or the number of days or weeks of any setting between them. Or, the predetermined conventional schedule can include using twice a day in the first week, and then using once a day for several months. In other embodiments, the present invention stipulates that the medicament can be taken orally, and taking opportunity depends on or does not depend on food intake. Therefore, for example, the medicament can be taken every morning and / or every night, no matter when the patient has eaten or when about to eat.

[1459] IV. Combination Therapy

[1460] In addition to use as a monotherapy, the compounds of the present disclosure can also be used in combination therapy. In certain embodiments, effective combination therapy is achieved with a single composition or pharmacological formulation comprising both agents, or with the simultaneous administration of two different compositions or formulations, one of which comprises a compound of the present invention and the other comprises a second agent. Alternatively, in other embodiments, the therapy precedes or follows treatment with the other agent with an interval ranging from minutes to months.

[1461] A variety of second therapies can be used in combination with the compounds of the present disclosure. Such second therapies include, but are not limited to, surgery, immunotherapy, radiotherapy, or a second chemotherapeutic agent. In certain embodiments, the second chemotherapeutic agent is an N-terminal Hsp90 inhibitor such as geldanamycin, radicicol, the geldanamycin derivative 17AAG, NVP-AUY922, or gamitrinib. A variety of different Hsp90 inhibitors that can be used in combination with the compounds provided herein are described in Jhaveri, et al., 2012, which is incorporated herein by reference.

[1462] V. Definitions

[1463] The following definitions supersede any conflicting definitions in any reference incorporated herein by reference. However, the fact that certain terms are defined should not be construed as indicating that any undefined term is undefined. Rather, all terms used are intended to describe the present invention in a manner that allows one of ordinary skill in the art to understand the scope of the present invention and practice the invention.

[1464] A. Chemical groups

[1465] When used in the context of chemical groups: "hydrogen" means -H; "hydroxy" means -OH; "oxo" means =O; "carbonyl" means -C(=O)-; "carboxyl" means -C(=O)OH (also written as -COOH or -CO2H); "halogen" independently means -F, -Cl, -Br or -I; "amino" means -NH2; "hydroxyamino" means -NHOH; "nitro" means -NO2; imino means =NH; " "Cyano" refers to -CN; "isonitrile" refers to -N=C=O; "azido" refers to -N3; ​​in a monovalent context, "phosphate" refers to -OP(O)(OH)2 or a deprotonated form thereof; in a divalent context, "phosphate" refers to -OP(O)(OH)O- or a deprotonated form thereof; "thiol" refers to -SH; and "thio" refers to =S; "sulfonyl" refers to -S(O)2-; and "sulfinyl" refers to -S(O)-.

[1466] In the context of chemical formulae, the symbol "-" refers to a single bond, "=" refers to a double bond, and "≡" refers to a triple bond. represents an optional bond, which, if present, is a single bond or a double bond. represents a single bond or a double bond. Covering, for example, It should be understood that no single ring atom forms part of more than one double bond. Furthermore, it should be noted that the covalent bond symbol "-" does not indicate any preferred stereochemistry when connecting one or two stereogenic atoms. Rather, it encompasses all stereoisomers and mixtures thereof. Symbol When drawn vertically through a bond (e.g., for a methyl group, Indicates the point of attachment for this group. It should be noted that attachment points are usually only identified in this way for larger groups to help the reader identify the point of attachment unambiguously. refers to a single bond where the group attached to the thick end of the wedge is "coming out of the page". refers to a single bond where the group attached to the thick end of the wedge is "entering the page". =Refers to a single bond, wherein the geometry around the double bond (e.g., E or Z) is undefined. Therefore, both options and their combinations are contemplated. On the atoms of the structures shown in this application, any undefined valence implicitly represents a hydrogen atom bonded to that atom. The bold dots on carbon atoms indicate that the hydrogen attached to that carbon is facing out of the page. Finally, groups containing specific functional groups and chemical classes such as -C(O)-alkanediyl (C≤6) -, used to indicate that the two elements can appear in any order, such as -C(O)-alkanediyl (C≤6) - or -alkanediyl (C≤6)-C(O)-. Alternatively, the group containing the chemical class and the variable or second chemical class appears in the order recited.

[1467] When a variable is described as a "floating group" on a ring system, for example, the group "R" in the formula:

[1468]

[1469] The variable may replace any hydrogen atom attached to any of the ring atoms, including depicted, implied, or explicitly defined hydrogens, so long as a stable structure results. When a variable is described as a "floating group" on a fused ring system, for example, the group "R" in the formula:

[1470]

[1471] Unless otherwise stated, this variable can replace any hydrogen that is connected to any ring atom of any ring in the fused ring.Replaceable hydrogen includes depicted hydrogen (for example, hydrogen connected to nitrogen in the above formula), implicit hydrogen (for example, not shown in the above formula but understood to be hydrogen present), well-defined hydrogen, and its existence depends on the optional hydrogen of the ring atom itself (for example, when X equals -CH-, hydrogen connected to group X), as long as stable structure is formed.In the example shown, R can be located on 5 yuan or 6 yuan ring of fused ring system.In the above formula, the subscript letter " y " that follows immediately after R in brackets represents numerical variable.Unless otherwise stated, this variable can be 0,1,2 or any integer greater than 2, is only limited to the maximum number of replaceable hydrogen atoms of ring or ring system.

[1472] For chemical groups and compound classes, the number of carbon atoms in the group or class is as follows: "Cn" defines the exact number of carbon atoms (n) in the group / class. "C≤n" defines the maximum number of carbon atoms (n) that can be in the group / class, while the minimum number is as small as possible for the group / class in question. For example, it is understood that in the group "alkyl" (C≤8) ", "Cycloalkanediyl (C≤8) ", "heteroaryl (C≤8) ” and “acyl (C≤8) ", the minimum number of carbon atoms is 1; in the group "alkenyl (C≤8) ", "Alkynyl (C≤8) " and "heterocycloalkyl (C≤8) ", the minimum number of carbon atoms is 2; in the group "cycloalkyl (C≤8) ", the minimum number of carbon atoms is 3; and in the group "aryl (C≤8) ” and “aromatic diyl (C≤8)", the minimum number of carbon atoms is 6. "Cn-n'" defines the minimum number (n) and maximum number (n') of carbon atoms in the group. Thus, "alkyl" (C2-10) ” refers to those alkyl groups having 2 to 10 carbon atoms. These carbon number indicators may precede or follow the chemical group or species they modify, and they may be enclosed in brackets or not without indicating any change in meaning. Thus, the terms “C5 olefins,” “C5-olefins,” “olefins” (C5) ” and “olefins C5 Except as noted below, each carbon atom is counted to determine whether a group or compound falls within the specified number of carbon atoms. For example, the group dihexylamino is dialkylamino (C＝12) An example of a group; however, it is not a dialkylamino (C＝6) Similarly, phenethyl is an aralkyl group (C＝8) When any chemical group or compound class defined herein is modified by the term "substituted", any carbon atoms in the moiety replacing a hydrogen atom are not counted. Thus, a methoxyhexyl group having a total of seven carbon atoms is a substituted alkyl group. (C1-6) Unless otherwise indicated, any chemical group or class of compounds listed in the claims without a carbon atom limitation has a carbon atom limitation of less than or equal to 12.

[1473] When used to modify a compound or chemical group, unless described below, the term "saturated" refers to a compound or chemical group that does not have a carbon-carbon double bond and a carbon-carbon triple bond. When the term is used to modify an atom, it refers to a portion of the atom that is not a double bond or a triple bond. In the case of a substituted form of a saturated group, one or more carbon-oxygen double bonds or carbon-nitrogen double bonds may be present. And when such a bond exists, the carbon-carbon double bond that may occur as a part of a keto-enol tautomerism or an imine / enamine tautomerism is not excluded. When the term "saturated" is used to modify a solution of a substance, it refers to a substance that can no longer dissolve in the solution.

[1474] The term "aliphatic" means that the compound or chemical group so modified is an acyclic or cyclic, but non-aromatic compound or group. In an aliphatic compound / group, the carbon atoms can be linked together in straight chains, branched chains, or non-aromatic rings (alicyclic). Aliphatic compounds / groups can be saturated, i.e., linked by a single carbon-carbon bond (alkanes / alkyls), or unsaturated, having one or more carbon-carbon double bonds (alkenes / alkenyls), or having one or more carbon-carbon triple bonds (alkynes / alkynyls).

[1475] The term "aromatic" means that the modified compound or chemical group has a planar unsaturated ring of atoms containing 4n+2 electrons in a completely conjugated cyclic π system. Aromatic compounds or chemical groups can be described as a single resonance structure; however, description of one resonance structure is also used to refer to any other resonance structure. For example:

[1476] Also used to indicate Aromatic compounds can also be depicted using circles to represent the delocalized nature of electrons in a fully conjugated cyclic π system, two non-limiting examples of which are shown below:

[1477]

[1478] The term "alkyl" when used without the "substituted" modifier means a monovalent saturated aliphatic group having one carbon atom as the point of attachment, having a straight or branched acyclic structure, and having no atoms other than carbon and hydrogen. The groups -CH3(Me), -CH2CH3(Et), -CH2CH2CH3(n-Pr or propyl), -CH(CH3)2(i-Pr, i Pr or isopropyl), -CH2CH2CH2CH3(n-Bu), -CH(CH3)CH2CH3(sec-butyl), -CH2CH(CH3)2(isobutyl), -C(CH3)3(tert-butyl, t-butyl, t-Bu or tThe term "alkanediyl," when used without the "substituted" modifier, refers to a divalent saturated aliphatic radical having one or two saturated carbon atoms as points of attachment, a straight or branched acyclic structure, no carbon-carbon double or triple bonds, and no atoms other than carbon and hydrogen. The groups -CH2-(methylene), -CH2CH2-, -CH2C(CH3)2CH2-, and -CH2CH2CH2- are non-limiting examples of alkanediyl radicals. "Alkanes" refers to the class of compounds having the formula HR, where R is an alkyl radical, as that term is defined above. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -C02H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2. The following groups are non-limiting examples of substituted alkyl groups: -CH2OH, -CH2Cl, -CF3, -CH2CN, -CH2C(O)OH, -CH2C(O)OCH3, -CH2C(O)NH2, -CH2C(O)CH3, -CH2OCH3, -CH2OC(O)CH3, -CH2NH2, -CH2N(CH3)2, and -CH2CH2Cl. The term "haloalkyl" is a subset of substituted alkyl groups in which the hydrogen atom replacement is limited to halo (i.e., -F, -Cl, -Br, or -I) such that no atoms other than carbon, hydrogen, and halogen are present. The group -CH2Cl is a non-limiting example of a haloalkyl group. The term "fluoroalkyl" is a subset of substituted alkyl groups in which the hydrogen atom replacement is limited to fluoro such that no atoms other than carbon, hydrogen, and fluorine are present. The groups -CH2F, -CF3, and -CH2CF3 are non-limiting examples of fluoroalkyl groups.

[1479] The term "cycloalkyl", when used without the "substituted" modifier, means a monovalent saturated aliphatic group having one carbon atom as the point of attachment, said carbon atom forming part of one or more non-aromatic ring structures, having no carbon-carbon double or triple bonds, and having no atoms other than carbon and hydrogen. Non-limiting examples include: -CH(CH2)2 (cyclopropyl), cyclobutyl, cyclopentyl, or cyclohexyl (Cy). As used herein, the term does not exclude the presence of one or more alkyl groups attached to a carbon atom of a non-aromatic ring structure (carbon number limitations permitting). The term "cycloalkanediyl", when used without the "substituted" modifier, means a divalent saturated aliphatic group having two carbon atoms as the points of attachment, having no carbon-carbon double or triple bonds, and having no atoms other than carbon and hydrogen. Group is a non-limiting example of a cycloalkanediyl group. "Cycloalkanes" refers to the class of compounds having the formula HR, in which R is cycloalkyl, as that term is defined above. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH, -NO, -COH, -COCH, -CN, -SH, -OCH, -OCHCH, -C(O)CH, -NHCH, -NHCHCH, -N(CH), -C(O)NH, -C(O)NHCH, -C(O)N(CH), -OC(O)CH, -NHC(O)CH, -S(O)OH, or -S(O)NH.

[1480] The term "alkenyl," when used without the "substituted" modifier, means a monovalent unsaturated aliphatic radical having one carbon atom as the point of attachment, having a linear or branched acyclic structure, at least one non-aromatic carbon-carbon double bond, no carbon-carbon triple bonds, and no atoms other than carbon and hydrogen. Non-limiting examples include: -CH=CH2 (vinyl), -CH=CHCH3, -CH=CHCH2CH3, -CH2CH=CH2 (allyl), -CH2CH=CHCH3, and -CH=CHCH=CH2. The term "alkenediyl," when used without the "substituted" modifier, means a divalent unsaturated aliphatic radical having two carbon atoms as the point of attachment, having a linear or branched acyclic structure, at least one non-aromatic carbon-carbon double bond, no carbon-carbon triple bonds, and no atoms other than carbon and hydrogen. The groups -CH=CH-, -CH=C(CH3)CH2-, -CH=CHCH2-, and -CH2CH=CHCH2- are non-limiting examples of alkenediyl groups. It should be noted that although alkenediyl groups are aliphatic, once attached at both ends, this does not preclude the group from forming part of an aromatic structure. The terms "alkene" and "olefin" are synonymous and refer to the class of compounds having the formula HR, where R is an alkenyl group, as that term is defined above. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have been independently replaced with -OH, -F, -Cl, -Br, -I, -NH, -NO, -COH, -COCH, -CN, -SH, -OCH, -OCHCH, -C(O)CH, -NHCH, -NHCHCH, -N(CH), -C(O)NH, -C(O)NHCH, -C(O)N(CH), -OC(O)CH, -NHC(O)CH, -S(O)OH, or -S(O)NH. The groups -CH=CHF, -CH=CHCl, and -CH=CHBr are non-limiting examples of substituted alkenyl groups.

[1481] The term "cycloalkenyl," when used without the "substituted" modifier, means a monovalent saturated aliphatic group having one carbon atom as the point of attachment, said carbon atom forming part of one or more non-aromatic ring structures, having one or more carbon-carbon double bonds, provided that the group remains non-aromatic, has no carbon-carbon triple bonds, and has no atoms other than carbon and hydrogen. Non-limiting examples include cyclopentenyl or cyclohexenyl. As used herein, the term does not exclude the presence of one or more alkyl groups (carbon number limitations permitting) attached to a carbon atom of the non-aromatic ring structure. The term "cycloalkenediyl," when used without the "substituted" modifier, means a divalent saturated aliphatic group having two carbon atoms as the point of attachment, having one or more carbon-carbon double bonds, provided that the group remains non-aromatic, has no carbon-carbon triple bonds, and has no atoms other than carbon and hydrogen. "Cycloalkene" refers to the class of compounds having the formula HR, wherein R is cycloalkenyl, as that term is defined above. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -C02H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2.

[1482] The term "alkynyl," when used without the "substituted" modifier, refers to a monovalent unsaturated aliphatic group having one carbon atom as the point of attachment, having a straight or branched acyclic structure, at least one carbon-carbon triple bond, and no atoms other than carbon and hydrogen. As used herein, the term alkynyl does not exclude the presence of one or more non-aromatic carbon-carbon double bonds. The groups -C≡CH, -C≡CCH3, and -CH2C≡CCH3 are non-limiting examples of alkynyl groups. "Alkynes" refers to the class of compounds having the formula HR, where R is an alkynyl group. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -C02H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2.

[1483] When used in the absence of " (being) substituted " modifier, term " aryl " represents the monovalent unsaturated aromatic group with an aromatic carbon atom as attachment point, this carbon atom forms a part for one or more aromatic ring structures, each aromatic ring structure has 6 ring atoms that are all carbon, and wherein this group is not composed of the atom except carbon and hydrogen.If there is more than one ring, then the ring can be fused or not fused.Unfused ring is connected by covalent bond.As used herein, term aryl does not exclude the presence of one or more alkyl groups (carbon number restriction allows) that are connected with the first aromatic ring or any additional aromatic ring that exists.The non-limiting example of aryl group comprises phenyl (Ph), methylphenyl, (dimethyl) phenyl ,-C6H4CH2CH3(ethylphenyl), naphthyl, and the monovalent group (for example, 4-phenylphenyl) derived from biphenyl. When used without the "(substituted)" modifier, the term "arene diyl" refers to a divalent aromatic group having two aromatic carbon atoms as points of attachment, the carbon atoms forming part of one or more 6-membered aromatic ring structures, each of which has 6 ring atoms that are all carbon, and wherein the divalent group is not composed of atoms other than carbon and hydrogen. As used herein, the term "arene diyl" does not exclude the presence of one or more alkyl groups connected to the first aromatic ring or any additional aromatic rings present (carbon number limitations permitting). If there is more than one ring, the rings may be fused or unfused. Unfused rings are connected by covalent bonds. Non-limiting examples of arene diyl groups include:

[1484]

[1485] "Aromatic hydrocarbons" refers to the class of compounds having the formula HR, in which R is an aryl group, as that term is defined above. Benzene and toluene are non-limiting examples of aromatic hydrocarbons. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH, -NO, -COH, -COCH, -CN, -SH, -OCH, -OCHCH, -C(O)CH, -NHCH, -NHCHCH, -N(CH), -C(O)NH, -C(O)NHCH, -C(O)N(CH), -OC(O)CH, -NHC(O)CH, -S(O)OH, or -S(O)NH.

[1486] The term "aralkyl," when used without the "substituted" modifier, refers to the monovalent group -alkanediyl-aryl, wherein the terms alkanediyl and aryl are each used in a manner consistent with the definitions provided above. Non-limiting examples are: phenylmethyl (benzyl, Bn) and 2-phenyl-ethyl. When the term aralkyl is used with the "substituted" modifier, one or more hydrogen atoms from the alkanediyl and / or aryl groups have been independently replaced with -OH, -F, -Cl, -Br, -I, -NH, -NO, -COH, -COCH, -CN, -SH, -OCH, -OCHCH, -C(O)CH, -NHCH, -NHCHCH, -N(CH), -C(O)NH, -C(O)NHCH, -C(O)N(CH), -OC(O)CH, -NHC(O)CH, -S(O)OH, or -S(O)NH. Non-limiting examples of substituted aralkyl groups are (3-chlorophenyl)-methyl and 2-chloro-2-phenyl-eth-1-yl.

[1487] The term "heteroaryl," when used without the "substituted" modifier, means a monovalent aromatic group having an aromatic carbon or nitrogen atom as the point of attachment, the carbon or nitrogen atom forming part of one or more aromatic ring structures, each having from 3 to 8 ring atoms, wherein at least one ring atom of the aromatic ring structure is nitrogen, oxygen, or sulfur, and wherein the heteroaryl group does not consist of atoms other than carbon, hydrogen, aromatic nitrogen, aromatic oxygen, and aromatic sulfur. If more than one ring is present, the rings are fused; however, the term heteroaryl does not exclude the presence of one or more alkyl or aryl groups attached to one or more ring atoms (carbon number limitations permitting). Non-limiting examples of heteroaryls include benzoxazolyl, benzimidazolyl, furanyl, imidazolyl (Im), indolyl, indazolyl (Im), isoxazolyl, methylpyridyl, oxazolyl, oxadiazolyl, phenylpyridyl, pyridyl (pyridyl), pyrrolyl, pyrimidinyl, pyrazinyl, quinolinyl, quinazolinyl, quinoxalinyl, triazinyl, tetrazolyl, thiazolyl, thienyl and triazolyl. The term "N-heteroaryl" refers to a heteroaryl group having a nitrogen atom as the point of attachment. "Heteroarene" refers to a class of compounds having the formula HR, wherein R is a heteroaryl group. Pyridine and quinoline are non-limiting examples of heteroarene. When these terms are used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2.

[1488] The term "heteroaralkyl," when used without the "substituted" modifier, refers to the monovalent group -alkanediyl-heteroaryl, wherein the terms alkanediyl and heteroaryl are each used in a manner consistent with the definitions provided above. Non-limiting examples are: pyridylmethyl and 2-furyl-ethyl. When the term heteroaralkyl is used with the "substituted" modifier, one or more hydrogen atoms from the alkanediyl and / or heteroaryl groups have been independently replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -C02H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2.

[1489] The term "heterocycloalkyl," when used without the "substituted" modifier, means a monovalent non-aromatic group having a carbon or nitrogen atom as the point of attachment, the carbon or nitrogen atom forming part of one or more non-aromatic ring structures, each non-aromatic ring structure having from 3 to 8 ring atoms, wherein at least one ring atom of the non-aromatic ring structure is nitrogen, oxygen, or sulfur, and wherein the heterocycloalkyl group does not consist of atoms other than carbon, hydrogen, nitrogen, oxygen, and sulfur. If more than one ring is present, the rings are fused. As used herein, the term does not exclude the presence of one or more alkyl groups attached to one or more ring atoms (carbon number limitations permitting). Furthermore, the term does not exclude the presence of one or more double bonds in a ring or ring system, provided that the resulting group remains non-aromatic. The non-limiting examples of heterocycloalkyl include aziridine, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, pyranyl, oxirane and oxetanyl. The term "N-heterocycloalkyl" means a heterocycloalkyl having a nitrogen atom as a point of attachment. N-pyrrolidinyl is an example of such a group. When these terms are used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2.

[1490] When used without the "substituted" modifier, the term "acyl" refers to a group -C(O)R, where R is hydrogen, alkyl, cycloalkyl, or aryl, as defined above. The groups -CHO, -C(O)CH (acetyl, Ac), -C(O)CHCH, -C(O)CH(CH), -C(O)CH(CH), -C(O)CHH, and -C(O)CHCH are non-limiting examples of acyl groups. "Thioacyl" is defined in a similar manner, but the oxygen atom of the group -C(O)R has been replaced by a sulfur atom, -C(S)R. The term "imino" refers to a divalent group =NR, which is defined in a similar manner to "acyl" or "thioacyl". The term "aldehyde" corresponds to an alkyl group as defined above that is attached to a -CHO group. When any of these terms is used with the “substituted” modifier, one or more hydrogen atoms (including the hydrogen atom directly attached to the carbon atom of the carbonyl or thiocarbonyl group, if any) have independently been replaced with —OH, —F, —Cl, —Br, —I, —NH2, —NO2, —C02H, —CO2CH3, —CN, —SH, —OCH3, —OCH2CH3, —C(O)CH3, —NHCH3, —NHCH2CH3, —N(CH3)2, —C(O)NH2, —C(O)NHCH3, —C(O)N(CH3)2, —OC(O)CH3, —NHC(O)CH3, —S(O)2OH, or —S(O)2NH2. The groups -C(O)CH2CF3, -CO2H(carboxy), -CO2CH3(methylcarboxy), -CO2CH2CH3, -C(O)NH2(carbamoyl), and -CON(CH3)2 are non-limiting examples of substituted acyl groups.

[1491] When used without the "substituted" modifier, the term "alkoxy" refers to a group -OR, where R is alkyl, as that term is defined above. Non-limiting examples include: -OCH3 (methoxy), -OCH2CH3 (ethoxy), -OCH2CH2CH3, -OCH(CH3)2 (isopropyloxy), or -OC(CH3)3 (tert-butyloxy). When used without the "substituted" modifier, the terms "cycloalkoxy," "alkenyloxy," "alkynyloxy," "aryloxy," "aralkyloxy," "heteroaryloxy," "heterocycloalkyloxy," "acyloxy," and "iminooxy" refer to groups defined as -OR, where R is, respectively, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heterocycloalkyl, acyl, and imino. The term "alkoxydiyl" refers to a divalent group -O-alkanediyl-, -O-alkanediyl-O-, or -alkanediyl-O-alkanediyl-. The terms "alkylthio" and "acylthio" when used without the "substituted" modifier refer to the group -SR, in which R is an alkyl group and an acyl group, respectively. The term "alcohol" corresponds to an alkane as defined above, in which at least one hydrogen atom has been replaced by a hydroxy group. The term "ether" corresponds to an alkane as defined above, in which at least one hydrogen atom has been replaced by an alkoxy group. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -C02H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2.

[1492] The term "alkylamino," when used without the "substituted" modifier, refers to the group -NHR, in which R is alkyl, as that term is defined above. Non-limiting examples include: -NHCH3 and -NHCH2CH3. The term "dialkylamino," when used without the "substituted" modifier, refers to the group -NRR', in which R and R' can be the same or different alkyl groups. Non-limiting examples of dialkylamino groups include: -N(CH3)2 and -N(CH3)(CH2CH3). The terms "cycloalkylamino," "alkenylamino," "alkynylamino," "arylamino," "aralkylamino," "heteroarylamino," "heterocycloalkylamino," and "alkoxyamino," when used without the "substituted" modifier, refer to the group defined as -NHR, in which R is cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heterocycloalkyl, and alkoxy, respectively. A non-limiting example of an arylamino group is -NHC6H5. The terms "dicycloalkylamino," "dialkenylamino," "dialkynylamino," "diarylamino," "diaralkylamino," "diheteroarylamino," "diheterocycloalkylamino," and "dialkoxyamino" refer to groups defined as -NRR', where R and R' are each cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heterocycloalkyl, and alkoxy, respectively. Similarly, the term alkyl(cycloalkyl)amino refers to a group defined as -NRR', where R is alkyl and R' is cycloalkyl. The term "acylamino," when used without the "substituted" modifier, refers to the group -NHR, where R is acyl, as that term is defined above. A non-limiting example of an acylamino group is -NHC(O)CH3. The term "alkylaminodiyl" refers to the divalent group -NH-alkanediyl-, -NH-alkanediyl-NH-, or -alkanediyl-NH-alkanediyl-. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms attached to the carbon atom have been independently replaced with -OH, -F, -Cl, -Br, -I, -NH, -NO, -C0H, -C0CH, -CN, -SH, -OCH, -OCHCH, -C(O)CH, -NHCH, -NHCHCH, -N(CH), -C(O)NH, -C(O)NHCH, -C(O)N(CH), -OC(O)CH, -NHC(O)CH, -S(O)OH, or -S(O)NH. The groups -NHC(O)OCH and -NHC(O)NHCH are non-limiting examples of substituted amido groups.

[1493] The term "alkylsulfonyl," when used without the "substituted" modifier, refers to the group -S(O)2R, in which R is alkyl, as that term is defined above. The terms "cycloalkylsulfonyl," "alkenylsulfonyl," "alkynylsulfonyl," "arylsulfonyl," "aralkylsulfonyl," "heteroarylsulfonyl," and "heterocycloalkylsulfonyl" are defined in a similar manner. When any of these terms is used with the "substituted" modifier, one or more hydrogen atoms have independently been replaced with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -C02H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -OC(O)CH3, -NHC(O)CH3, -S(O)2OH, or -S(O)2NH2.

[1494] "Hydroxy protecting groups" are well understood in the art. A hydroxy protecting group is a group that blocks the reactivity of a hydroxy group during a reaction to modify some other part of a molecule and can be easily removed to generate the desired hydroxy group. Hydroxy protecting groups are described at least in Greene and Wuts, 1999, which is incorporated herein by reference. Some non-limiting examples of hydroxy protecting groups include: acyl groups such as formyl, acetyl, propionyl, pivaloyl, tert-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and the like; sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl, and the like; acyloxy groups such as benzyloxycarbonyl (Cbz), p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, Methoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenyl)-1-methylethoxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, diphenylmethoxycarbonyl, tert-butoxycarbonyl (Boc), diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl (Alloc), 2,2,2-trichloroethoxycarbonyl, 2-trimethylsilylethyloxycarbonyl (Teoc), phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl (Fmoc), cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl, etc.; aralkyl groups such as benzyl, triphenylmethyl, benzyloxymethyl, etc.; and silyl groups such as trimethylsilyl, etc. Protected hydroxyl groups are groups of the formula: -OR PGH , where R PGH is a hydroxy protecting group, which is as defined above.

[1495] B. Other Definitions

[1496] When used in conjunction with the term "comprising" in the claims and / or the specification, the use of the word "a" or "an" can mean "one", but it is also consistent with the meaning of "one or more", "at least one", and "one or more than one".

[1497] Throughout this application, the term "about" is used to indicate that a value includes the variation in error inherent in the device or method used to determine the value, or the variation that exists between study subjects. Unless otherwise defined in a manner consistent with the above, the term "about" is used to indicate a value that is within ±5% of the listed value. In certain specific embodiments, the term "about" is ±1% of the listed value.

[1498] An "active ingredient" (AI) or active pharmaceutical ingredient (API) (also referred to as active compound, active substance, active agent, pharmaceutical agent, reagent, bioactive molecule, or therapeutic compound) is the biologically active component of a drug.

[1499] The terms "comprises," "having," and "include" are open-ended linking verbs. Any form or tense of one or more of these verbs, such as "comprises," "comprising," "has," "having," "includes," and "including," are also open-ended. For example, any method that "comprises," "has," or "includes" one or more steps is not limited to having only those one or more steps and also encompasses other, unlisted steps.

[1500] The term "effective," as this term is used in this specification and / or claims, means sufficient to achieve a desired, expected, or intended result. When used in the context of treating a patient or subject with a compound, "effective amount," "therapeutically effective amount," or "pharmaceutically effective amount" means an amount of such a compound that, when administered to a patient or subject, is sufficient to achieve such treatment or prevention of a disease, as these terms are defined below.

[1501] " Excipient " is the pharmaceutically acceptable substance that is prepared together with the active ingredient of medicine, pharmaceutical composition, preparation or drug delivery system. Excipient can be used, for example, make composition stable, make composition expand (therefore when using for this purpose, often referred to as " extender ", " filler " or " diluent "), or give therapeutic enhancement to the active ingredient in final dosage form, for example, promote drug absorption, reduce viscosity or improve solubility. Excipient includes the pharmaceutically acceptable form of antiadherent, adhesive, coating agent, pigment, disintegrant, flavoring agent, glidant, lubricant, preservative, adsorbent, sweetener and vehicle. The main excipient that serves as the medium of transport active ingredient is commonly referred to as vehicle. Except auxiliary in vitro stability, such as preventing from being denatured or gathering in the expected shelf life, excipient can also be used in manufacturing process, for example, the processing of auxiliary active substance, such as by promoting powder flowability or non-stick performance to realize. The suitability of excipient usually can depend on route of administration, dosage form, active ingredient and other factors and change.

[1502] The term "hydrate," when used as a modifier of a compound, means that the compound has less than one (e.g., hemihydrate), one (e.g., monohydrate), or more than one (e.g., dihydrate) molecule of water associated with each molecule of the compound (e.g., a solid form of the compound).

[1503] The term "IC 50 ” represents the inhibitory dose that obtains 50% of the maximal response. This quantitative measure indicates the amount of a particular drug or other substance (inhibitor) required to inhibit a given biological, biochemical, or chemical process (or component of a process, i.e., an enzyme, cell, cell receptor, or microorganism) by half.

[1504] An "isomer" of a first compound is an individual compound wherein each molecule contains the same constituent atoms as the first compound, but wherein the three-dimensional configuration of those atoms is different.

[1505] As used herein, the term "patient" or "subject" refers to a living mammalian organism, such as a human, monkey, cow, sheep, goat, dog, cat, mouse, rat, guinea pig, or a transgenic species thereof. In certain embodiments, the patient or subject is a primate. Non-limiting examples of human patients are adults, adolescents, infants, and fetuses.

[1506] As used generally herein, "pharmaceutically acceptable" refers to compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues, organs and / or body fluids of humans and animals without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit / risk ratio.

[1507] "Pharmaceutically acceptable salts" refers to salts of the compounds disclosed herein that are pharmaceutically acceptable as defined above and possess the desired pharmacological activity. Such salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or organic acids such as 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, 2-naphthalenesulfonic acid, 3-phenylpropionic acid, 4,4'-methylenebis(3-hydroxy-2-ene-1-carboxylic acid), 4-methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, acetic acid, aliphatic mono- and dicarboxylic acids, aliphatic sulfuric acid, aromatic sulfuric acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, carbonic acid, Pharmaceutically acceptable salts include hydroxybenzoic acid, cinnamic acid, citric acid, cyclopentanepropionic acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, enanthic acid, caproic acid, hydroxynaphthoic acid, lactic acid, lauryl sulfuric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, muconic acid, o-(4-hydroxybenzoyl) benzoic acid, oxalic acid, p-chlorobenzenesulfonic acid, phenyl-substituted alkanoic acid, propionic acid, p-toluenesulfonic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, tartaric acid, tert-butylacetic acid, trimethylacetic acid, etc. Pharmaceutically acceptable salts also include base addition salts, which can be formed when the acidic protons present are capable of reacting with inorganic bases or organic bases. Acceptable inorganic bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide, and calcium hydroxide. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, etc. It will be appreciated that the particular anion or cation forming part of any salt of the invention is not critical so long as the salt as a whole is pharmacologically acceptable. Other examples of pharmaceutically acceptable salts and methods for their preparation and use are presented in Handbook of Pharmaceutical Salts: Properties, and Use (P.H. Stahl & C.G. Wermuth, eds., Verlag Helvetica Chimica Acta, 2002).

[1508] A "pharmaceutically acceptable carrier," "drug carrier," or simply "carrier" is a pharmaceutically acceptable substance formulated with an active ingredient drug that participates in the carriage, delivery, and / or transport of a chemical agent. Drug carriers can be used to improve the delivery and effectiveness of drugs, including, for example, controlled-release technologies to modulate drug bioavailability, reduce drug metabolism, and / or reduce drug toxicity. Some drug carriers may improve the effectiveness of drug delivery to a specific target site. Examples of carriers include: liposomes, microspheres (e.g., made of poly(lactic-co-glycolic acid) copolymers), albumin microspheres, synthetic polymers, nanofibers, protein-DNA complexes, protein conjugates, red blood cells, virosomes, and dendrimers.

[1509] A "pharmaceutical drug" (also known as a drug, drug product, pharmaceutical composition, pharmaceutical formulation, pharmaceutical product, medicinal product, medicine, medicament, or simply drug, medicament or formulation) is a composition used for the diagnosis, cure, treatment or prevention of disease, which comprises an active pharmaceutical ingredient (API) (as defined above) and, optionally, one or more inactive ingredients, which are also known as excipients (as defined above).

[1510] "Prevention" or "preventing" includes: (1) inhibiting the onset of a disease in a subject or patient, wherein the subject or patient may be at risk for and / or susceptible to the disease, but has not yet experienced or manifested any or all of the symptoms or signs of the disease; and / or (2) slowing the onset of symptoms or signs of a disease in a subject or patient, wherein the subject or patient may be at risk for and / or susceptible to the disease, but has not yet experienced or manifested any or all of the symptoms or signs of the disease.

[1511] " prodrug " refers to the compound that can be converted into the inhibitor according to the present invention by metabolism in vivo. Prodrug itself also may have or not have activity to given target protein. For example, the compound comprising hydroxyl can be used as ester, and this ester is converted into hydroxy compound by hydrolysis in vivo. The non-limiting example of the suitable ester that can be converted into hydroxy compound in vivo comprises acetate, citrate, lactate, phosphate, tartrate, malonate, oxalate, salicylate, propionate, succinate, fumarate, maleate, methylene-bis-β-hydroxy naphthoate, gentisate, isethionate, di-p-toluoyl tartrate, mesylate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexyl aminosulfonate, quinate and amino acid ester. Similarly, the compound comprising amine can be used as amide, and this amide is converted into amine compound by hydrolysis in vivo.

[1512] "Stereoisomers" or "optical isomers" are isomers of a given compound in which the same atoms are bonded to the same other atoms, but in which the three-dimensional configurations of those atoms are different. "Enantiomers" are stereoisomers of a given compound that are mirror images of each other like left and right hands. "Diastereomers" are stereoisomers of a given compound that are not enantiomers. Chiral molecules contain a chiral center (also called a stereocenter or stereocenter), which is any point (but not necessarily an atom) in a molecule that carries multiple groups such that the interchange of any two groups will produce a stereoisomer. In organic compounds, the chiral center is usually a carbon, phosphorus, or sulfur atom, but other atoms can also serve as stereocenters in organic and inorganic compounds. A molecule can have multiple stereocenters, giving rise to its many stereoisomers. In compounds whose stereoisomerism is attributable to a tetrahedral stereocenter (e.g., tetrahedral carbon), it is assumed that the total number of possible stereoisomers will not exceed 2. n , where n is the number of tetrahedral stereocenters. Molecules with symmetry often have a smaller number than the maximum possible number of stereoisomers. A 50:50 mixture of enantiomers is called a racemic mixture. Alternatively, a mixture of enantiomers can be enantiomerically enriched so that one enantiomer is present in an amount greater than 50%. Generally, enantiomers and / or diastereomers can be resolved or separated using techniques known in the art. It is expected that for any stereocenter or chiral axis whose stereochemistry has not yet been defined, the stereocenter or chiral axis can exist in its R form, S form, or as a mixture of R and S forms (including racemic mixtures and non-racemic mixtures). As used herein, the phrase "substantially free of other stereoisomers" means that the composition contains ≤15%, more preferably ≤10%, even more preferably ≤5%, or most preferably ≤1% of one or more other stereoisomers.

[1513] "Treatment" or "treating" includes (1) inhibiting the disease in a subject or patient who is experiencing or exhibiting symptoms or signs of the disease (e.g., arresting further development of the symptoms and / or signs), (2) ameliorating the disease in a subject or patient who is experiencing or exhibiting symptoms or signs of the disease (e.g., reversing the symptoms and / or signs), and / or (3) achieving any measurable reduction in the disease or its symptoms in a subject or patient who is experiencing or exhibiting symptoms or signs of the disease.

[1514] Other abbreviations used in this article are as follows: DMSO, dimethyl sulfoxide; OCR, oxygen consumption rate; ECAR, extracellular acidification rate; MRC, maximal respiratory capacity; FCCP, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; PBST, phosphate-buffered saline containing 0.1% Tween 20; HRP, horseradish peroxidase; EDTA, ethylenediaminetetraacetic acid; DMEM, Dulbecco's modified Eagle's medium; EtOAc, ethyl acetate; NMO, N-methylmorpholine N-oxide; THF, tetrahydrofuran, Me, methyl; NMR, nuclear magnetic resonance; DMF, N,N-dimethylformamide; TBAI, tetrabutylammonium iodide; GDA, geldanamycin; or, BN or Bn, benzyl.

[1515] The term "unit dose" refers to a formulation of a compound or composition that is prepared in a manner sufficient to provide a single therapeutically effective dose of the active ingredient to a patient in a single administration. Such unit dose formulations that can be used include, but are not limited to, a single tablet, capsule, or other oral formulation, or a single vial of a liquid or other injectable formulation that can be injected with a syringe.

[1516] VI. Examples

[1517] The following examples are included to demonstrate preferred embodiments of the present invention. It will be appreciated by those skilled in the art that the techniques disclosed in the following examples represent techniques discovered by the inventors to function well in the practice of the present invention and thus can be considered to constitute preferred modes for its practice. However, it will be appreciated by those skilled in the art, in view of this disclosure, that many changes can be made in the disclosed specific embodiments and still obtain similar or similar results without departing from the spirit and scope of the present invention.

[1518] A. Compounds and Synthesis

[1519] Solution 1

[1520]

[1521] Reagents and conditions: a) 3-F-PhB(OH)2, Na2CO3, Pd(PPh3)4, DME, H2O, reflux, 70%; b) NBS, CH2Cl2, CHCl3, room temperature, 75%; c) acrylamide, N,N-diisopropylethylamine, Pd(OAc)2, P(o-Tol)3, DMF, ~130-135°C, 81%; d) H2 (1 atmosphere), 10% Pd / C, THF, room temperature, 95%; e) i) NaOH, PhI(OAc)2, THF, H2O; ii) HCl, EtOAc, 77%; f) i) NaOH, EtOH, H2O, <15°C; ii) NaHCO3, Ac2O, ~0-5°C; g) NaOH, ~0-5°C, 97%.

[1522] Option 2

[1523]

[1524] Reagents and conditions: a) BnOH, AcCl, 30°C, 91%; b) 2,2-DMP, TsOH·H2O, acetone, 20-25°C, 85%; c) Me2SO4, TBAB, 40% aqueous NaOH, CPME, 20-30°C, q.s.; d) H2 (0.5 MPa), 10% Pd / C, CPME, 30°C, 85%; e) NaClO, NaBr, NaOA c) TEMPO, H2O, CH2Cl2, 20-30°C, 73%; f) MeMgBr, Et2O, CPME, 20-35°C, 88%; g) NaClO, NaBr, NaOAc, TEMPO, H2O, CH2Cl2, 20-30°C, 75%; h) DIBAL-H, CH2Cl2, -25°C to -5°C, 97%; i) 1) 732 ion exchange resin, H2O, 40°C; 2) IRA96RF, 93%; j) PhCOCl, pyridine, 0°C to room temperature, 57%.

[1525] Option 3

[1526]

[1527] Reagents and conditions: a) PhCOCl, pyridine, 15° C., 61%.

[1528] Option 4

[1529]

[1530] Reagents and conditions: a) BzCl, Py, 0-15°C, 93%; b) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature; c) NaOH, MeOH, THF, H2O, room temperature, 81% from 23.

[1531] Option 5

[1532]

[1533] Reagents and conditions: a) 2,2-DMP, acetone, TsOH·H2O, 10℃, 83%; b) NaH, THF, 0℃; MeI, 15℃, 86%; c) 0.2M aqueous H2SO4, 80℃, 90%; d) BzCl, Py, 0-15℃, 68%; e) A1, BF3·OEt2, CH2Cl2, 0℃, 69%; f) NaOH, MeOH, THF, H2O, room temperature, 89%.

[1534] Option 6

[1535]

[1536] Reagents and conditions: (a) A1, BF3·OEt2, CH2Cl2, 0°C, 61% for 31; 3% for 32; (b) K2CO3, MeOH, room temperature, 98% for T3; 80% for T4.

[1537] Option 7

[1538]

[1539] Reagents and conditions: a) 2,2-DMP, acetone, (S)-CSA, room temperature, 98%; b) FSO2CF2CO2H, CuI, MeCN, 60°C, 28%; c) 6N aqueous HCl, MeOH, 0°C, 76%.

[1540] Option 8

[1541]

[1542] Reagents and conditions: a) 2,2-DMP, acetone, (S)-CSA, room temperature, 97%; b) FSO2CF2CO2H, CuI, MeCN, 60°C, 51%; c) 6N aqueous HCl, MeOH, room temperature, 66%.

[1543] Option 9

[1544]

[1545] Reagents and conditions: a) NaH, BnBr, DMF, 0°C to room temperature, 75%; b) 6N aqueous HCl, MeOH, room temperature, 51%.

[1546] Plan 10

[1547]

[1548] Reagents and conditions: a) NaH, i-PrI, DMF, room temperature to 65°C, 37%; b) 70% AcOH aqueous solution, room temperature to 40°C, 47%.

[1549] Plan 11

[1550]

[1551] Reagents and conditions: a) DAST, CH2Cl2, 0°C, 23%; b) 6N aqueous HCl, MeOH, room temperature, 67%.

[1552] Plan 12

[1553]

[1554] Reagents and conditions: a) MeNH2·HCl, Et3N, CH2Cl2, 0°C, 12%; b) 3, DIPEA, Pd(OAc)2, tri(o-tolyl)phosphine, DMF, 135°C, 84%; c) H2, 10% Pd / C, THF, room temperature, 93%.

[1555] Plan 13

[1556]

[1557] Reagents and conditions: a) A2, BF3·OEt2, CH2Cl2, 0°C, 62% for 43; b) 1N aqueous NaOH, THF, MeOH, room temperature, 60% for T10 from 23; 95% for T11.

[1558] Plan 14

[1559]

[1560] Reagents and conditions: a) n-BuLi, (CO2Me)2, THF, -78°C, 17%; b) DAST, 1,2-dichloroethane, 60°C, 58%; c) NaBH4, EtOH, 0°C to room temperature, 97%; d) i) Tf2O, pyridine, MeCN, 0°C; ii) aqueous NH4OH, room temperature; e) Ac2O, Py, CH2Cl2, 0°C, from 46 to 79%; f) H2, 10% Pd / C, THF, room temperature, q.s.

[1561] Plan 15

[1562]

[1563] Reagents and conditions: a) A3, BF3·OEt2, CH2Cl2, 0°C; b) 1N aqueous NaOH, THF, MeOH, room temperature, 42% from 18 and 19.

[1564] Plan 16

[1565]

[1566] Reagents and conditions: a) A3, BF3·OEt2, CH2Cl2, 0°C, 42%; b) 1N aqueous NaOH, THF, MeOH, room temperature, 87%.

[1567] Plan 17

[1568]

[1569] Reagents and conditions: a) BBr3, CH2Cl2, 0℃, 90%; b) 23, BF3·OEt2, CH2Cl2, 0℃, 75%; c) NaBH4, EtOH, 0℃ to room temperature, 74%; d) i) Tf2O, pyridine, MeCN, 0℃; ii) NH4OH aqueous solution, room temperature; e) Ac2O, Py, EtOAc, 0℃, from 52 to 40%; f) 1N NaOH aqueous solution, THF, MeOH, room temperature, 76%.

[1570] Plan 18

[1571]

[1572] Reagents and conditions: a) Ac2O, Py, DMAP, 0℃ to room temperature, quant.; b) A1, BF3·OEt2, CH2Cl2, 0℃ to room temperature, 70%; c) 10% aqueous NaOH, MeOH, room temperature, 42%.

[1573] Plan 19

[1574]

[1575] Reagents and conditions: a) BzCl, Py, 0°C to room temperature, 94%; b) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 57%; c) 1N aqueous NaOH, MeOH, THF, room temperature, 71%.

[1576] Plan 20

[1577]

[1578] Reagents and conditions: a) BzCl, Py, 0°C to room temperature, 95%; b) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 50%; c) 1N aqueous NaOH, MeOH, THF, room temperature, 62%.

[1579] Plan 21

[1580]

[1581] Reagents and conditions: a) Tf2NPh, K2CO3, THF, microwave, 120°C, 62%; b) 3-F-PhB(OH)2, Pd(dppf)Cl2, K2CO3, DMF, 75°C, 97%; c) t-BuOK, isoamyl nitrite, t-BuOH, THF, room temperature, 47%; d) In, AcOH, Ac2O, THF, 70°C, 84%; e) H2, 10% Pd / C, EtOAc, room temperature, 89%.

[1582] Plan 22

[1583]

[1584] Reagents and conditions: a) A5, BF3·OEt2, CH2Cl2, room temperature, 46%; b) NaBH4, EtOH, 0°C, 94%; c) 1N aqueous NaOH, EtOH, room temperature, 81%.

[1585] Plan 23

[1586]

[1587] Reagents and conditions: a) A5, BF3·OEt2, CH2Cl2, 0°C, 24%; b) NaBH4, MeOH, 0°C, 82%; c) 1N aqueous NaOH, MeOH, room temperature, 67%.

[1588] Plan 24

[1589]

[1590] Reagents and conditions: a) A1, BF3.OEt2, toluene, 0°C, 79%; b) i) K2CO3, MeOH, room temperature, 64% for T0; ii) column chromatography.

[1591] Plan 25

[1592]

[1593] Reagents and conditions: a) NH4Br, ethylenediamine, 130°C, Biotage microwave, 97%.

[1594] Plan 26

[1595]

[1596] Reagents and conditions: a) A1, AgOTf, MS, CH2Cl2, room temperature, quant.; b) 1 N aqueous NaOH, EtOH, room temperature, 36%.

[1597] Plan 27

[1598]

[1599] Reagents and conditions: a) BBr3, CH2Cl2, 0℃ to room temperature, ≤85%; b) 3,4-dihydro-2H-pyran, PPTS, CH2Cl2, room temperature, 56%; c) K2CO3, BnBr, 0℃ to room temperature, 66%; d) 3-F-PhB(OH)2, Pd(dppf)Cl2, K2CO3, DMF, 90℃, 67%; e) MeNO2, NH4OA c, 65°C; f) LiAlH4, THF, 0°C; g) NaOAc, Ac2O, room temperature, 33% from 80; h) PPTS, EtOH, 65°C, 86%; i) 18 and 19, BF3·OEt2, CH2Cl2, room temperature, 62%; j) 1N aqueous NaOH, EtOH, 82%; k) H2, 10% Pd / C, EtOAc, room temperature, 83%.

[1600] Plan 28

[1601]

[1602] Reagents and conditions: a) BnBr, K2CO3, DMF, room temperature, quant.; b) 3-F-phenylboronic acid, K2CO3, Pd(dppf)Cl2, 1,4-dioxane, 90°C, 95%; c) pyridine HCl, DMF, microwave 200°C, 23%; d) MOMCl, DIPEA, CH2Cl2, room temperature, 95%; e) MeNO2, NH4OAc, 65°C, 97%; f) LiAlH4, THF, 45°C, 94%; g) NaOAc, Ac2O, room temperature, 31%; h) 3N aqueous HCl, THF, 67%; i) 18 and 19, BF3·OEt2, MS, CH2Cl2, room temperature, 15%; j) 1N aqueous NaOH, EtOH, room temperature, 56%; k) 10% Pd / C, H2, EtOAc, quant.

[1603] Plan 29

[1604]

[1605] Reagents and conditions: a) BnBr, K2CO3, DMF, room temperature, 50%; b) pyridine HCl, DMF, microwave 200°C, 49%; c) 3-F-PhB(OH)2, K2CO3, Pd(dppf)Cl2, 1,4-dioxane, 90°C, 79%; d) MOMCl, DIPEA, CH2Cl2, room temperature, quant.; e) MeNO2, NH4OAc, 65°C, 99%; f) LiAlH4, THF, 45°C, 95%; g) NaOAc, Ac2O, room temperature, 40%; h) 3N aqueous HCl, THF, 66%; i) 10% Pd / C, H2, EtOAc, quant.; j) 18 and 19, BF3OEt2, MS, CH2Cl2, room temperature, 15% for 104, 22% for 105; k) 1N aqueous NaOH, EtOH, room temperature, 55% for T25; 35% for T26.

[1606] Plan 30

[1607]

[1608] Reagents and conditions: a) PhMgBr, Et2O, THF, 0°C, 37% for 106; 50% for 107; b) PDC, MgSO4, CH2Cl2, room temperature, 59%; c) DIBAL-H, toluene, CH2Cl2, 0°C, 96%; d) A1, Ph3P, DIAD, THF, room temperature, 55%; e) HOAc, water, 40°C, 44% for T27; 15% for T28.

[1609] Plan 31

[1610]

[1611] Reagents and conditions: a) NaBH4, MeOH, 0°C to room temperature, quant.; b) TBDMSCl, Et3N, DMAP, CH2Cl2, room temperature, 36% for 112; 35% for 113; c) TBAF, THF, 0°C, 77%; d) IPh(OAc)2, TEMPO, CH2Cl2, room temperature, 83%; e) DIBAL-H, toluene, CH2Cl2, 0°C, 92%; f) 50W X2 hydrogen resin, MeCN, H2O, 40℃, q.s.; g) PhCOCl, DMAP, pyridine, room temperature, 70%; h) A1, BF3OEt2, MS, CH2Cl2, room temperature, 65%; i) 1N aqueous NaOH, EtOH, room temperature, 77%.

[1612] Plan 32

[1613]

[1614] Reagents and conditions: a) TBAF, THF, 0°C; b) IPh(OAc)2, TEMPO, CH2Cl2, room temperature, 74% from 113; c) DIBAL-H, toluene, CH2Cl2, 0°C, 93%; d) 50W X2 hydrogen resin, MeCN, H2O, 40℃, q.s.; e) PhCOCl, DMAP, pyridine, room temperature, 77%; f) A1, BF3OEt2, MS, CH2Cl2, rt, 65%; g) 1N aqueous NaOH, EtOH, rt, 24% for T30; 44% for T31.

[1615] Plan 33

[1616]

[1617] Reagents and conditions: a) Allylmagnesium bromide, Et2O, MTBE, room temperature; b) PDC, MgSO4, CH2Cl2, room temperature, quant.; c) DIBAL-H, toluene, CH2Cl2, 0°C, quant.; d) A1, Ph3P, DIAD, THF, room temperature, 48%; e) HOAc, water, 40°C, 18% for T32; 15% for T33; f) 10% Pd / C, H2, EtOAc, room temperature, 79% for T34; 90% for T35.

[1618] Plan 34

[1619]

[1620] Reagents and conditions: a) Grubbs Catalyst TM 2nd generation, CH2Cl2, room temperature, 81%; b) 50W X2 hydrogen resin, MeCN, H2O, room temperature, 93%; c) PhCOCl, DMAP, pyridine, room temperature, 85%; d) A1, BF3OEt2, MS, CH2Cl2, room temperature, 32%; e) 1N aqueous NaOH, EtOH, room temperature, 49%; f) 10% Pd / C, H2, EtOAc, room temperature, 63%.

[1621] Plan 35

[1622]

[1623] Reagents and conditions: a) Allylmagnesium bromide, Et2O, THF, 0°C to rt, 66%; b) NaBH4, MeOH, 0°C to rt, quant.; c) IPh(OAc)2, TEMPO, CH2Cl2, rt, 28% for 136; 24% for 137.

[1624] Plan 36

[1625]

[1626] Reagents and conditions: a) DIBAL-H, toluene, CH2Cl2, 0°C, 92%; b) 50W X2 hydrogen resin, MeCN, water, 40 ° C, 91%; c) PhCOCl, DMAP, pyridine, room temperature, 76%; d) H2, 10% Pd / C, EtOAc, room temperature, 89%; e) A1, BF3OEt2, MS, CH2Cl2, rt, 56%; f) 1N aqueous NaOH, EtOH, rt, 30% for T38; 12% for T39.

[1627] Plan 37

[1628]

[1629] Reagents and conditions: a) Ac2O, pyridine, room temperature; b) A1, BF3OEt2, MS, CH2Cl2, room temperature, 66% from 143; c) NaOMe, MeOH, 50°C, 63%.

[1630] Plan 38

[1631]

[1632] Reagents and conditions: a) Tf2O, pyridine, CH2Cl2, 0℃, 71%; b) CsF, t-pentanol, 110℃, 57%; c) A1, BF3·OEt2, MS, CH2Cl2, room temperature, 83%; d) NaOMe, MeOH, room temperature, 58%.

[1633] Plan 39

[1634]

[1635] Reagents and conditions: a) allyl alcohol, Sc(OTf)3, 100℃, 50%; b) 2,2-DMP, acetone, CH2Cl2, p-TsOH·H2O, room temperature, 95%; c) NaH, PhCH2Cl, DMF, 0℃ to room temperature, 89%; d) 50W X2 hydrogen resin, MeCN, H2O, 45°C, 98%; e) i) Wilkinson catalyst, 1,4-diazobicyclo[2.2.2]octane, EtOH, benzene, H2O, 80°C; ii) 1N aqueous HCl, acetone, 60°C, 85%; f) Ac2O, pyridine, room temperature, 69%; g) A1, BF3·OEt2, MS, CH2Cl2, rt, 57%; h) NaOMe, MeOH, rt, 79%.

[1636] Plan 40

[1637]

[1638] Reagents and conditions: a) isobutylmagnesium bromide, THF, room temperature, 62%; b) NaBH4, EtOH, 0°C to room temperature, 84%; c) TBSCl, Et3N, DMAP, CH2Cl2, room temperature, 39% for 159; 35% for 160.

[1639] Plan 41

[1640]

[1641] Reagents and conditions: a) TBAF, THF, room temperature, quant.; b) PhI(OAc)2, TEMPO, CH2Cl2, room temperature, 88%; c) DIBAL-H, toluene, CH2Cl2, room temperature, 98%; d) AG50X-W2 resin, MeCN / water, 40°C, quant.; e) BzCl, pyridine, room temperature, 86%; f) A1, BF3·OEt2, MS, room temperature, 62%; g) 1 N aqueous NaOH, EtOH, room temperature, 26% for T45; 35% for T46.

[1642] Plan 42

[1643]

[1644] Reagents and conditions: a) TBAF, THF, room temperature, quant.; b) PhI(OAc)2, TEMPO, CH2Cl2, room temperature, 69%; c) DIBAL-H, toluene, CH2Cl2, room temperature, 98%; d) AG50X-W2 resin, MeCN, water, 40°C, 99%; e) BzCl, pyridine, room temperature, 93%; f) A1, BF3·OEt2, MS, room temperature, 61%; g) 1 N aqueous NaOH solution, EtOH, room temperature, 86%.

[1645] Plan 43

[1646]

[1647] Reagents and conditions: a) TBDMSCl, Et3N, DMAP, CH2Cl2, 61%; b) i-BuMgBr, THF, room temperature, 92%; c) TBAF, THF, room temperature, 67%; d) PhI(OAc)2, TEMPO, CH2Cl2, room temperature, 74%; e) DIBAL-H, toluene, CH2Cl2, room temperature, quant.; f) AG50X-W2 resin, MeCN, water, 40°C, quant.; g) BzCl, pyridine, room temperature, 93%; h) Al, BF3·OEt2, MS, room temperature, 20%; i) 1N aqueous NaOH solution, EtOH, room temperature, 34%.

[1648] Plan 44

[1649]

[1650] Reagents and conditions: a) Allylmagnesium bromide, THF, room temperature, 93%; b) NaBH4, EtOH, MeOH, 0°C to room temperature, quant.; c) TBSCl, Et3N, DMAP, CH2Cl2, room temperature, 33% for 183; 42% for 184.

[1651] Plan 45

[1652]

[1653] Reagents and conditions: a) TBAF, THF, room temperature, quant.; b) PhI(OAc)2, TEMPO, CH2Cl2, room temperature, 66%; c) DIBAL-H, toluene, CH2Cl2, room temperature, 97%; d) AG50X-W2 resin, MeCN / water, 40°C, 87%; e) BzCl, pyridine, room temperature, 70%; f) A1, BF3·OEt2, MS, room temperature, 39%; g) 1N aqueous NaOH, EtOH, room temperature, 29% for T49; 20% for T50; h) O3 / O2, CH2Cl2:MeOH, -78°C; NaBH4, -78°C to room temperature, 45% for T40; 47% for T41.

[1654] Plan 46

[1655]

[1656] Reagents and conditions: a) TBAF, THF, room temperature, quant.; b) PhI(OAc)2, TEMPO, CH2Cl2, room temperature, 63%; c) DIBAL-H, toluene, CH2Cl2, room temperature, quant.; d) AG50X-W2 resin, MeCN / water, 40°C, 93%; e) BzCl, pyridine, room temperature, 78%; f) A1, BF3·OEt2, MS, rt, 59%; g) 1N aqueous NaOH, EtOH, rt, 98%; h) H2, 10% Pd / C, EtOAc, rt, 92%.

[1657] Plan 47

[1658]

[1659] Reagents and conditions: a) O3 / O2, CH2Cl2, MeOH, -78°C; NaBH4, -78°C to room temperature, 44%.

[1660] Plan 48

[1661]

[1662] Reagents and conditions: a) i) TsCl, pyridine, 0°C to room temperature; ii) Ac2O, room temperature, 97%; b) NaI, acetone, reflux, 92%; c) H2, 10% Pd / C, MeOH, room temperature; Ac2O, pyridine, room temperature, 31%; d) Al, BF3OEt2, MS, CH2Cl2, room temperature, 69%; e) NaOMe, MeOH, room temperature, 71%.

[1663] Plan 49

[1664]

[1665] Reagents and conditions: a) PhCH2Br, Ag2O, benzene, room temperature, 24%; b) A1, BF3OEt2, MS, CH2Cl2, room temperature, 76%; c) NaOMe, MeOH, room temperature, 51%.

[1666] Plan 50

[1667]

[1668] Reagents and conditions: a) 3-F-PhB(OH)2, Ba(OH)2·8H2O, Pd(dppf)Cl2, 1,4-dioxane, H2O, 80℃, 27%; b) i) Zn(BD4)2, THF, toluene, reflux; ii) saturated NaHCO3 aqueous solution, Ac2O, EtOAc, 0℃, 50%; c) BBr3, CH2Cl2, 0℃, 76%.

[1669] Plan 51

[1670]

[1671] Reagents and conditions: a) A6, BF3·OEt2, CH2Cl2, 0°C, 74%; c) K2CO3, MeOH, room temperature, 76%.

[1672] Plan 52

[1673]

[1674] Reagents and conditions: a) benzyl acrylate, Pd(OAc)2, P(o-Tol)3, DIPEA, DMF, room temperature to 130°C, 91%; b) 10% Pd / C, EtOAc, H2, 96%; c) 18, BF3·OEt2, CH2Cl2, 0°C, 57%; d) i) (COCl)2, DMF, CH2Cl2, 0°C to room temperature. ii) NH2CH3·HCl, Et3N, CH2Cl2, room temperature, 76%; e) K2CO3, MeOH, room temperature, 49%.

[1675] Plan 53

[1676]

[1677] Reagents and conditions: a) Ac2O, Py, DMAP, 0℃ to room temperature, 79%; b) A1, BF3·OEt2, CH2Cl2, 0℃ to room temperature, 54%; c) 1N aqueous NaOH, MeOH, THF, room temperature, 52%.

[1678] Plan 54

[1679]

[1680] Reagents and conditions: a) Ac2O, Py, DMAP, 0℃ to room temperature, 84%; b) A1, BF3·OEt2, CH2Cl2, 0℃ to room temperature, 45%; c) 1N aqueous NaOH, MeOH, THF, room temperature, 61%.

[1681] Plan 55

[1682]

[1683] Reagents and conditions: a) Ac2O, Py, DMAP, 0℃ to room temperature, 94%.; b) A1, BF3·OEt2, CH2Cl2, 0℃ to room temperature, 67%; c) 1N aqueous NaOH, MeOH, room temperature, 75%.

[1684] Plan 56

[1685]

[1686] Reagents and conditions: a) Ac2O, Py, DMAP, 0°C to room temperature, 94%; b) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 24% for 220; 20% for 221; c) 1N aqueous NaOH, MeOH, THF, room temperature, 68% for T61; 80% for T62.

[1687] Plan 57

[1688]

[1689] Reagents and conditions: a) NaOMe, MeOH, THF, 0°C, appropriate amount (quant.)

[1690] Plan 58

[1691]

[1692] Reagents and conditions: a) NaH, DMF, BnBr, 0°C to room temperature, quant.; b) 2N aqueous HCl, AcOH, H2O, 95°C, 78%; c) MeMgCl, Et2O, THF, 0°C to room temperature, 97%; d) DMSO, (COCl)2, CH2Cl2, -78°C; Et3N, -78°C to room temperature, quant.; e) LDA, THF, hexanes, -78°C, 37% for 227; f) POCl3, Py, 0°C to room temperature, 67%; g) CuBr·Me2S, AlMe3, THF, 0°C to room temperature Room temperature, 92%; h) Zn(BH4)2, Et2O, 0°C, 96%; i) Tf2O, Py, CH2Cl2, 0°C, 88%; j) 222, 18-crown-6, DMF, 0°C, 24%; k) H2, 10% Pd / C, THF, room temperature, 91%; l) 2,2-DMP, acetone, (S)-CSA, room temperature, 87%; m) NaH, MeI, DMF, 0°C; n) NaH, MeI, DMF, room temperature, 99%; o) 6N aqueous HCl, MeOH, room temperature, 37% for T64 from 234; 84% for T65 from 236.

[1693] Plan 59

[1694]

[1695] Reagents and conditions: a) Tf2NPh, Et3N, CH2Cl2, 0°C to room temperature, quant.; b) Bis(pinacolato)diboron, KOAc, Pd(dppf)Cl2, DMF, 130°C, 61%; c) NaIO4, THF, water, 1N aqueous HCl, room temperature, 83%.

[1696] Plan 60

[1697]

[1698] Reagents and conditions: a) Co(acac)3, TMEDA, 2-methyl-1-propenylmagnesium bromide, THF, 0°C to room temperature, 26%; b) 1N aqueous NaOH, MeOH, 0°C to room temperature, 77%; c) NaH, BnBr, DMF, 0°C to room temperature, 88%; d) i) O3, MeOH, CH2Cl2, -78°C; ii) NaBH4, 0°C to room temperature, 68%; e) CBr4, PPh3, pyridine, room temperature to 65°C, 88%; f) 239, NiI2, trans-2-aminocyclohexane alcohol hydrochloride, NaHMDS, 2-BuOH, 60°C, 54%; g) H2, 10% Pd / C, THF, room temperature, 95%;

[1699] Plan 61

[1700]

[1701] Reagents and conditions: a) Tebbe's reagent, pyridine, toluene, THF, -45°C to 0°C, 53%; b) i) 9-BBN, THF, 0°C to room temperature; ii) NaHCO3, water, room temperature; iii) 237, Pd(dppf)Cl2, DMF, room temperature to 60°C; c) 6M aqueous HCl, MeOH, room temperature, 8% for T67 from 247; 15% for T68 from 247.

[1702] Plan 62

[1703]

[1704] Reagents and conditions: a) Pd2(dba)3,4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), i-Pr2EtN, 2-ethylhexyl 3-mercaptopropionate, 1,4-dioxane, reflux, 92%; b) NaOMe, MeOH, room temperature, 50%.

[1705] Plan 63

[1706]

[1707] Reagents and conditions: a) 250, BF3·OEt2, CH2Cl2, 0°C, 80%; b) K2CO3, MeOH, room temperature, 68% for T69; 9% for T70.

[1708] Plan 64

[1709]

[1710] Reagents and conditions: a) 250, BF3.OEt2, CH2Cl2, 0°C to room temperature, 55% for the major anomer; b) K2CO3, MeOH, room temperature, 95%.

[1711] Plan 65

[1712]

[1713] Reagents and conditions: a) BF3·OEt2, CH2Cl2, 0°C to RT, 59% for 253; 73% for 254; b) H2, 10% Pd / C, EtOAc, RT, 76% for 255; 61% for 256; c) Ac2O, NaOAc, RT, quantitative for 257; 95% for 258; d) K2CO3, THF, MeOH, RT, 10% for T72; 23% for T73.

[1714] Plan 66

[1715]

[1716] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature; c) NaOH, MeOH, H2O, room temperature, from 259 to 50%.

[1717] Plan 67

[1718]

[1719] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 64%; c) NaOH, MeOH, THF, H2O, room temperature, 71%.

[1720] Plan 68

[1721]

[1722] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 56%; c) NaOH, MeOH, THF, H2O, room temperature, 75%.

[1723] Plan 69

[1724]

[1725] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 35%; c) NaOH, MeOH, THF, H2O, room temperature, 49%.

[1726] Plan 70

[1727]

[1728] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 76%; c) NaOH, MeOH, THF, H2O, room temperature, 77%.

[1729] Plan 71

[1730]

[1731] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 74%; c) NaOH, MeOH, THF, H2O, room temperature, 58%.

[1732] Plan 72

[1733]

[1734] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 15%; c) NaOH, MeOH, THF, H2O, room temperature, 12%.

[1735] Plan 73

[1736]

[1737] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C-reflux, 19%; c) NaOH, MeOH, THF, H2O, room temperature, 29%.

[1738] Plan 74

[1739]

[1740] Reagents and conditions: a) A1, BF3·OEt2, CH2Cl2, 0°C to room temperature, 41%; c) NaOH, MeOH, THF, H2O, room temperature, 15%.

[1741] B. Characterization

[1742] Unless otherwise stated, commercial reagents were used as received, and all reactions were performed under nitrogen. Formamidines were prepared from the corresponding nitrile or carboxylic acid ester using the procedures reported in the literature (Garigipati, 1990), unless otherwise stated. All solvents were HPLC or ACS grade. Spectrophotometers were used at 400 MHz ( 1 H NMR) or 100 MHz ( 13 Nuclear magnetic resonance (NMR) spectra are recorded at the operating frequency of the CNMR. Chemical shifts (δ) are expressed relative to the residual solvent (usually chloroform, for 1H NMR is given in ppm (δ = 7.26 ppm), and coupling constants (J) are given in Hz. Multiplicities are tabulated as: s for singlet, d for doublet, t for triplet, q for quartet, and m for multiplet. Mass spectra were recorded on a Waters Micromass ZQ or Agilent 6120 mass spectrometer.

[1743] Compound 2: A flask containing compound 1 (2818 g, 10.71 mol), (3-fluorophenyl)boronic acid (1574 g, 11.25 mol) and Na2CO3 (1135.1 g, 10.71 mol, 1 equivalent) was evacuated and refilled with argon three times. Deionized water (5.6 L), DME (14 L) and Pd(PPh3)4 (123.8 g, 0.107 mol) were added in sequence. The resulting mixture was degassed and refilled with argon three times, then refluxed for 7 h. The suspension was passed through The mixture was filtered through a plug of 500 g. The filtrate was a two-phase mixture. The organic phase was separated. The aqueous phase was extracted with EtOAc (10 L). The combined organic extracts were dried over Na2SO4 (3 kg), filtered, and concentrated. Half of the crude product was purified by column chromatography (silica gel, eluted with 20% CH2Cl2 in hexanes) to obtain compound 2 (1040 g, 70% yield) as a white solid.

[1744] Compound 3: To a solution of 2 (1020 g, 3.67 mol) in CHCl (6.12 L, 6 vol) and chloroform (510 mL) was added NBS (717.8 g, 4.04 mol) in one portion. The mixture was stirred at room temperature for 38 h. HPLC indicated that the reaction proceeded to completion. The mixture was washed with a 10% aqueous NaSO solution (6 L) and water (3×6 L). The organic phase was dried over NaSO (650 g), filtered, and concentrated. The residue was recrystallized from hexane (3 L), filtered, and washed with hexane (500 mL) to afford compound 3 (980.4 g, 75% yield) as a white solid. 1 H NMR (400MHz, CDCl3) δ7.54 (d, J=8.8Hz, 1H), 7.45-7.32 (m, 6H), 7.17 (ddd, J=7.7, 1.7, 1.0H z, 1H), 7.15-7.04 (m, 2H), 6.95 (d, J = 3.1Hz, 1H), 6.86 (dd, J = 8.8, 3.1Hz, 1H), 5.07 (s, 2H).

[1745] Compound 4: A flask was charged with compound 3 (104.6 g, 292.82 mmol), Pd(OAc)2 (658 mg, 2.93 mmol, 1 mol%), P(o-Tol)3 (1.79 g, 5.88 mmol) and DMF (520 mL). The stirred mixture was evacuated and refilled with argon four times. Acrylamide (24.98 g, 351.44 mmol) and N,N-diisopropylethylamine (45.42 g, 351.44 mmol) were then added. The resulting mixture was heated at about 130-135°C for 16 h. The mixture was cooled to room temperature and then passed through (26g) plug. The product of 4-nitropropene (5-nitropropene) (5-nitropropene) (6-nitropropene) (7-nitropropene) (8-nitropropene) (9-nitropropene) (10-nitropropene) (30-nitropropene) (8-nitropropene) (9-nitropropene) (8 ...

[1746] Compound 5: To a solution of compound 4 (530 g, 1.53 mol) in THF (6.90 L) was added 10% Pd / C (25 g). The mixture was stirred at room temperature under H2 (1 atm) for 28 h. An additional amount of 10% Pd / C (7.4 g) was added. The mixture was hydrogenated for another 8 h. The mixture was passed through The mixture was filtered through a plug of celite (100 g) and the filter cake was washed with THF (500 mL). The filtrate was concentrated to give compound 5 (377.9 g, 95% yield) as a viscous oil which solidified upon standing. m / z = 260.1 (M+1).

[1747] Compound 6: Compound 5 (388.7 g, 1.50 mol) was suspended in THF (2.33 L) and cooled to 0°C. A solution of NaOH (390 g, 9.75 mol) in water (1.17 L) was added while maintaining the reaction mixture below 15°C. The mixture was then cooled to 0°C and PhI(OAc)2 (531.5 g, 1.65 mol) was added portionwise. The reaction mixture was stirred at about 0-5°C for 2.5 h and then quenched by dropwise addition of HCl (12N aqueous solution, 570 mL, 6.84 mol) while maintaining the reaction temperature at about 0-5°C. After the addition was complete, the pH of the reaction mixture was about 8-9. The mixture was allowed to stand for 10 min. The resulting two phases were separated. The aqueous phase was extracted with EtOAc (2×2 L). The combined organic phases were washed with brine (2 L) and concentrated to dryness. The residue was suspended in EtOAc (2 L) and treated with HCl (4 M in EtOAc, 2 L). The mixture was vigorously stirred for 5 h and filtered. The filter cake was washed with EtOAc (1 L) and dried at 50 ° C to give compound 6 (309.2 g, 77% yield) as a brown solid. m / z = 232.1 (M + 1 of the free amine).

[1748] A1: Compound 6 (348.1 g, 1.30 mol) suspended in EtOH (2.09 L) was cooled to 0°C. A solution of NaOH (57.2 g, 1.43 mol) in water (700 mL) was added. During the addition, the internal temperature was maintained below 15°C. The mixture was stirred at 0-5°C for 0.5 h. NaHCO₃ (229.3 g, 2.73 mmol) was then added, and the mixture was stirred for 0.5 h. Ac₂O (139.4 g, 1.37 mol) was added dropwise at approximately 0-5°C, and the resulting suspension was stirred for 0.5 h. HPLC analysis indicated that compound 6 was consumed to yield a mixture of compound A1 (95.1%) and compound 7 (3.6%). NaOH (130 g, 3.25 mol) was then added portionwise at approximately 0-5°C. The mixture was stirred for 0.5 h. HCl (12 M, 300 mL, 3.6 mol) was added dropwise. The mixture was concentrated to remove most of the EtOH. The residue was diluted with water (700 mL) and extracted with ethyl acetate (1.7 L, then 2×350 mL). The combined organic extracts were dried over Na 2 SO 4 , filtered, and concentrated to afford Compound A1 (346.5 g, 97% yield) as a brown oil. m / z=274.1 (M+1); 1H NMR (400MHz, CD3CN) δ7.35(td,J=8.0,6.0Hz,1H),7.12(d,J=8.3Hz,1H),7.09-7.00(m,2H),6.97(ddd,J=9.6,2.6,1.6Hz,1H),6.80(d d,J=8.3,2.7Hz,1H),6.71(d,J=2.7Hz,1H),6.35(s,1H),5.36(m,1H),3.27(td,J=7.3,6.0Hz,2H),2.71(t,J=7.2Hz,2H),1.88(s,3H).

[1749] Compound 9: At 10-15°C under N2, a 20 L flask was charged with benzyl alcohol (2.5 L). Acetyl chloride (393 g, 5.01 mol) was added at 10-15°C over 30 min. The mixture was heated to 30°C and stirred for 1 h. Compound 8 (500 g, 3.33 mol) was added. The mixture was stirred at 30°C for 18 h. MTBE (5 L) was added. The mixture was stirred at 30°C for 18 h and then filtered. The filter cake was transferred to a 20 L flask and slurried with MTBE (5 L) at 30°C for 18 h and filtered. The resulting filter cake was slurried again with MTBE (5 L) at 30°C for 18 h and filtered. The filter cake was dried under vacuum at 35°C for 20 h to obtain compound 9 (730 g, 91% yield) as a white solid.

[1750] Compound 10: A reaction flask equipped with an overhead stirrer and temperature probe was charged with compound 9 (500 g, 2.08 mol) and acetone (2.5 L) at 15°C. The mixture was stirred for 5 minutes, and p-toluenesulfonic acid monohydrate (19.76 g, 0.10 mol) and 2,2-dimethoxypropane (1.08 kg, 10.37 mol) were added sequentially at 20-25°C. The mixture was stirred for 2.5 hours, and 5% aqueous NaHCO3 (2.5 L) was added over 30 minutes. CPME (5 L) was added, and the mixture was stirred for 20 minutes. The organic layer was separated and washed with water (3.75 L + 1.5 L) and 10% aqueous NaCl (2.5 L). The solution containing compound 10 (498.6 g, 85% yield) was used directly in the next step. 1H NMR (400MHz, CDCl3) δ7.46-7.28(m,5H),4.93(d,J=3.6Hz,1H),4.79(d,J=11.7Hz,1H),4.55(d,J=11.7Hz,1H),4.27-4.17(m,2H),4.01( dd,J=13.2,2.6Hz,1H),3.93(dd,J=13.2,1.3Hz,1H),3.80(ddd,J=7.4,6.3,3.6Hz,1H),2.21(d,J=7.7Hz,1H),1.53(s,3H),1.36(s,3H).

[1751] Compound 11: A reaction flask equipped with an overhead stirrer and a temperature probe was charged with a solution of compound 10 (344 g, 1.23 mol) obtained in the last step in CPME at room temperature. 40% aqueous NaOH (1.72 L), tetrabutylammonium bromide (39.65 g, 0.12 mol), and dimethyl sulfate (264 g, 2.09 mol) were added sequentially at 20-30°C. The mixture was stirred at 20-25°C for 20 h. Aqueous ammonia (approximately 25%-28% by weight, 689 g, 4.92 mol) was added. The mixture was stirred for 1 h, cooled to 0-5°C, and washed sequentially with water (1.72 L), 10% aqueous citric acid (1.03 L), 5% aqueous NaHCO₃ (1.03 L), and 10% aqueous NaCl (1.03 L). The organic layer was mixed with NaSO (344 g) and activated charcoal (3.44 g) and stirred at 20-30°C for 10 h. The mixture was filtered, and the filter cake was washed with CPME. The combined filtrate and washings contained compound 11 (380.6 g, quantitative yield). The solution was used directly in the next step.

[1752] Compound 12: An autoclave was charged with a solution of compound 11 (706 g, 2.40 mol) in CPME and 10% Pd / C (70.6 g) at room temperature. The autoclave was purged with N2 and then with H2. The mixture was hydrogenated at 0.5 MPa ...

Claims

1. A compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ; R8, R9 and R 10 are independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 is hydrogen, carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ; R8 and R9 are each independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; R 10 is amino or alkylamino (C≤6) , dialkylamino (C≤12) , acylamino (C≤12) or a substituted form of any of these three groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 is carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ; R7′ is hydrogen, carboxyl or alkyl (C3-8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ;or R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; R8, R9 and R 10 are independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2 or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ; R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; R8, R9 and R 10 are independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 0, 1, or 2; Y1 is a substituted -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or substituted -C(O)-alkanediyl (C≤6) -; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ;or R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; R8, R9 and R 10 are independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 1 or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ;or R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ; R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ;or R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; R8 is halogen, alkoxy (C3-6) , acyloxy (C≤6) , aralkyloxy (C≤12) or a substituted form of any of these groups; R9 and R 10 are independently halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 and R7' are each independently hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ; R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; R8, R9 and R 10 are independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ; R7′ is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ; R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; R8 is halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Or a compound of the formula: in: R 16 It is an alkyl (C≤12) , Cycloalkyl (C≤12) , aromatic (C≤18) , heteroaryl (C≤18) or a substituted form thereof; R 17 and R 18 are independently hydrogen, alkyl (C≤8) or substituted alkyl (C≤8) ; R 19 Is carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted R 19 ' is hydrogen, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ; R 20 , R 21 and R 22 are independently halogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups, or a protected hydroxyl group; Or a pharmaceutically acceptable salt of any one of the above formulae.

2. The compound according to claim 1, further defined as: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ; R8, R9 and R 10 are independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or a pharmaceutically acceptable salt of said formula.

3. The compound according to any one of claims 1 to 2, further defined as: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) - or a substituted form of any of these groups; Y2 is CH2, O or S; R3 is -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; R7 is carboxyl or alkyl (C≤6) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is an alkyl (C≤12) , substituted alkyl (C≤12) , arylalkyl (C≤12) or substituted aralkyl (C≤12) ;and R8, R9 and R 10 are independently hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups; or a pharmaceutically acceptable salt of said formula.

4. The compound according to any one of claims 1 to 3, wherein the compound is further defined as: or a pharmaceutically acceptable salt of any of these formulae.

5. A pharmaceutical composition comprising: (A) the compound according to any one of claims 1 to 4; and (B) Excipients.

6. A method of treating a disease or disorder in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or composition according to any one of claims 1 to 5.

7. A method for inducing the expression of Hsp70 protein, comprising contacting the protein with an effective amount of the compound or composition according to any one of claims 1 to 5, which is sufficient to induce the expression of the Hsp70 protein.

8. A method for inhibiting Hsp90 protein, comprising contacting the protein with an effective amount of the compound or composition according to any one of claims 1 to 5, which is sufficient to inhibit the activity of the Hsp90 protein.

9. A compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) -, -alkanediyl (C≤6) -C(O)R 17 or a substituted form of any of these groups, wherein: R 17 It is an alkyl (C≤6) or substituted alkyl (C≤6) ; Y2 is a hydroxyl group or a thiol group; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is carboxyl, -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently absent, hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , aralkyloxy (C≤12) , substituted aralkyloxy (C≤12) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; and X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; Provided that the compound is not a compound of the formula:

10. A method for preparing a compound according to any one of claims 1 to 4, comprising reacting (a) with (b) in the presence of a coupling agent: (a) a compound of the formula: in: n is 0, 1, or 2; Y1 is -alkanediyl (C≤6) -、-C(O)-alkanediyl (C≤6) -, -alkanediyl (C≤6) -C(O)R 17 or a substituted form of any of these groups, wherein: R 17 It is an alkyl (C≤6) or substituted alkyl (C≤6) ; Y2 is a hydroxyl group or a thiol group; R1 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , acylamino (C≤6) , alkoxy (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 is hydrogen, amino, halogen, hydroxy, carboxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , arylalkyl (C≤12) , acylamino (C≤6) , alkoxy (C≤6) , alkylthio (C≤6) , alkylsulfonyl (C≤6) or a substituted form of any of these groups; R2 and R 15 together and is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; R3 is carboxyl, -NR 11 R 11 ' or -C(O)NR 12 R 12 ',in: R 11 and R 11 ' are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) or substituted acyl (C≤6) ; R 12 and R 12 ' are each independently hydrogen, alkyl (C≤6) or substituted alkyl (C≤6) ; R4, R5 and R6 are each independently absent, hydrogen, halogen, alkyl (C≤6) , substituted alkyl (C≤6) , alkoxy (C≤6) , substituted alkoxy (C≤6) , aralkyloxy (C≤12) , substituted aralkyloxy (C≤12) , acyloxy (C≤6) or substituted acyloxy (C≤6) ; X1 is CR 14 or N, where: R 14 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; or R 14 and R 15 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; X2 is CR 15 or N, where: R 15 is hydrogen, halogen, hydroxyl or alkyl (C≤6) , alkenyl (C≤6) , alkynyl (C≤6) , alkoxy (C≤6) , alkylamino (C≤6) , -alkanediyl (C≤6) -Heterocycloalkyl (C≤8) or a substituted form of any of these groups; R 15 and R 14 together and is an alkanediyl (C≤6) , olefin diyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; or R 15 Together with R2, it is an alkanediyl (C≤6) , alkoxydiyl (C≤6) , alkylaminodiyl (C≤6) or a substituted form of any of these groups; (b) a compound of the formula: in: n is 0, 1, or 2; Y3 is hydroxyl, halogen, acyloxy (C≤8) , iminooxy (C≤8) or a substituted form of any of these groups; R7 and R7' are each independently hydrogen, hydroxy, carboxyl or alkyl (C≤8) , alkenyl (C≤8) , alkynyl (C≤8) , Cycloalkyl (C≤8) , heterocycloalkyl (C≤8) , aromatic (C≤12) , heteroaryl (C≤12) , arylalkyl (C≤12) , heteroarylalkyl (C≤12) , -alkanediyl (C≤6) -OR 13 or a substituted form of any of these groups, wherein: R 13 It is aralkyl (C≤12) or substituted aralkyl (C≤12) ; R7 and R7' are together and are -alkanediyl (C≤7) -, -Olefindiyl (C≤7) - or a substituted form of any of these groups; and R8, R9 and R 10 are independently hydrogen, hydroxy or alkyl (C≤6) , alkoxy (C≤6) , acyl (C≤6) , acyloxy (C≤6) , arylalkyl (C≤12) , aralkyloxy (C≤12) or a substituted form of any of these groups.

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