Novel functionalized lactams as modulators of 5-hydroxytryptamine receptor 7 and method of using the same

Abstract

To provide methods of treating diseases.SOLUTION: Pharmaceutical compositions of the invention comprise functionalized lactam derivatives of a formula (I) having a disease-modifying action in treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity. A is selected from a group consisting of (group) and (group). As described in detail and specifically demonstrated herein, surprisingly, a remarkable effect is achieved according to the present invention, and this remarkable effect has not been able to be easily predicted from a prior art by those skilled in the art.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 62 / 670,116, filed May 11, 2018, which is incorporated herein by reference in its entirety.

[0002] Statement of Federally Funded Research The U.S. Government has a paid-up license in this invention and, in limited circumstances, the right to require the patent owner to license it to others on reasonable terms, as provided for in Grant No. 143DK115254-01 awarded by the National Institute of Diabetes and Digestive and Kidney Disease, and Grant No. HHSN-271-2008-00025-C awarded by the National Institute of Mental Health.

[0003] Embodiments of the present invention are directed to novel compounds useful as modulators of 5-hydroxytryptamine receptor 7 (5-HT7) activity, and methods of use thereof. Embodiments are further directed to novel chemical species useful in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity. [Background technology]

[0004] Serotonin, discovered in the late 1940s, is present in both the peripheral and central nervous systems [Physiol.Res.,60(2011)15-25; Psychopharmacology,213(2011)167-169]. Serotonin, or 5-hydroxytryptamine (5-HT), is an indolealkylamine monoamine neurotransmitter that acts at neuronal synapses. Seven distinct families of serotonin receptors have been identified, and at least 20 subgroups have been cloned based on sequence similarity, signaling binding, and pharmacological properties. The seven 5-HT receptor families are named 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7, and each of these receptors, in turn, has subfamilies or subgroups. The signaling mechanisms of all seven members of the family have been studied, and it is known that activation of 5-HT1 and 5-HT5 receptors decreases intracellular cAMP, while activation of 5-HT2, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors increases intracellular IP3 and DAG. The 5-HT pathway in the brain is an important target for drug development in the field of CNS disorders. This neurotransmitter binds to G protein-coupled receptors and is involved in, among other things, cognition, mood, anxiety, attention, appetite, cardiovascular function, vasoconstriction, and sleep (ACS Medicinal Chemistry). Letters, 2011, 2, 929-932, Physiological Research, 2011, 60, 15-25), inflammatory bowel disease (IBD), and enteritis (WO2012 / 058769, Khan, WI, et. al. Journal of Immunology, 2013, 190, 4795-4804), epilepsy, seizure disorders (Epilepsy Research (2007) 75, 39), drug and alcohol addiction (Hauser, SR et. al. Frontiers in Neuroscience, 2015, 8, 1-9). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2012 / 058769 [Non-patent literature]

[0006] [Non-Patent Document 1] Physiol.Res,60(2011)15-25 [Non-patent document 2] Psychopharmacology 213(2011)167-169 [Non-patent document 3] ACS Medicinal Chemistry Letters,2011,2,929-932, [Non-patent document 4] Physiological Research,2011,60,15-25 [Non-patent document 5] Khan,WI,et.al.Journal of Immunology,2013,190,4795-4804 [Non-patent document 6] Epilepsy Research (2007) 75, 39 [Non-Patent Document 7] Hauser,SRet.al.Frontiers in Neuroscience,2015,8,1-9 Summary of the Invention [Means for solving the problem]

[0007] The present invention relates to a compound of formula (I), which is a novel 5-hydroxytryptamine receptor 7 (5-HT7) activity modulator: [ka] The present invention is directed to enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof, wherein: A, [ka] is selected from the group consisting of R 1 But hydrogen, C 1-6 Straight chain alkyl, C 3-7 branched alkyl; R 2 But hydrogen, C 1-6 Straight chain alkyl, C 3-7 branched alkyl; Or R 1 and R 2 together with the atoms to which they are attached form a ring having 5 to 7 ring atoms, optionally containing a double bond, or or R 1 and R 2 together with the atoms to which they are attached, form O, S, SO, SO2, and NR 7 forming a ring having 6 to 8 ring atoms containing a moiety selected from the group consisting of R 3 optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, and [ka] is selected from the group consisting of R 4 optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, and [ka] is selected from the group consisting of R 5optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, and [ka] is selected from the group consisting of R 6 is selected from the group consisting of optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, and optionally substituted 4-pyridyl; R 7 is H, C1-6 straight chain alkyl, C3-7 branched alkyl, C3-7 cycloalkyl, optionally substituted phenyl, optionally substituted benzyl, COR 8 , CO2R 9 ,CONR 10a R 10b , SO2NR 10a R 10b , and SO2R 10c is selected from the group consisting of R 8 But H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 9 But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 10a But H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 10b But H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R10c But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C1-6 straight-chain haloalkyl, C3-7 branched haloalkyl, -(CH2) q CN, -(CH2) q SO2R 11 , -(CH2) q OR 12 , [ka] is selected from the group consisting of R 11 But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 12 But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 1a , R 1b , R 1c , R 1d , and R 1e independently in each occurrence: H, OH, NO2, halogen, CN, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, -S(C 1-6 Straight chain alkyl), S(C 3-7 Branched alkyl), -S(C 3-7 cycloalkyl), COR 13 , CO2R 14 ,CONR 15a R 15b , SO2NR 15a R 15b , N.R. 16a R16b , N.R. 16a COR 17 , N.R. 16a SO2R 18 , and N.R. 16a SO2NR 19a R 19b is selected from the group consisting of R 13 But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 14 but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 15a But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 15b But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 16a But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 16b But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 17 But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 18but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 19a but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 19b but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl; n is 1, 2, 3, or 4; m is 1, 2, or 3. In an embodiment, A is [ka] In embodiments, n is 1, 2, or 3. In embodiments, n is 1 or 2. In embodiments, n is 1. In embodiments, n is 2. In embodiments, R 1 and R 2 Each of the 1-6 alkyl (e.g., R 1 and R 2 is methyl or R 1 and R 2 and each of R is ethyl. 1 and R 2 together with the atoms to which they are attached form a 5- to 8-membered ring (e.g., C3-C8 cycloalkyl, C5-C8 cycloalkenyl, or NR 7 In one embodiment, R 1 and R 2together with the atom to which they are attached form cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, pyrrolidinyl, or piperidinyl, and the nitrogen atom in the pyrrolidinyl or piperidinyl group is NR 7 In an embodiment, R 7 is alkylsulfonyl-SO2R 10c (e.g., -SO2Me), or acyl-COR 8 (e.g., acetyl). In embodiments, R 3 is phenyl or pyridyl. In embodiments, R 3 is unsubstituted. In embodiments, R 3 is substituted (e.g., phenyl substituted with 1, 2, 3, 4, or 5 substituents, or pyridyl substituted with 1, 2, 3, or 4 substituents). In embodiments, the substituents are -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino. In an embodiment, A is [ka] In embodiments, n is 1, 2, or 3. In embodiments, n is 1 or 2. In embodiments, n is 1. In embodiments, n is 2. In embodiments, R 1 and R 2 Each of the 1-6 alkyl (e.g., R 1 and R 2 is methyl or R 1 and R 2 and each of R is ethyl. 1 and R 2together with the atoms to which they are attached form a 5- to 8-membered ring (e.g., C3-C8 cycloalkyl, C5-C8 cycloalkenyl, or NR 7 In one embodiment, R 1 and R 2 together with the atom to which they are attached form cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, pyrrolidinyl, or piperidinyl, and the nitrogen atom in the pyrrolidinyl or piperidinyl group is NR 7 In an embodiment, R 7 is alkylsulfonyl-SO2R 10c (e.g., -SO2Me), or acyl-COR 8 (e.g., acetyl). In embodiments, R 4 is phenyl or pyridyl. In embodiments, R 4 is unsubstituted. In embodiments, R 4 is substituted (e.g., phenyl substituted with 1, 2, 3, 4, or 5 substituents, or pyridyl substituted with 1, 2, 3, or 4 substituents). In embodiments, the substituents are -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i Pr, -CF3, cyclopentyl, cyclohexyl The aryl group is selected from the group consisting of xyl, pyrrolidinyl, piperidinyl, and morpholino.

[0008] In an embodiment, A is [ka] In embodiments, n is 1, 2, or 3. In embodiments, n is 1 or 2. In embodiments, n is 1. In embodiments, n is 2. In embodiments, R 1 and R 2Each of the 1-6 alkyl (e.g., R 1 and R 2 is methyl or R 1 and R 2 and each of R is ethyl. 1 and R 2 together with the atoms to which they are attached form a 5- to 8-membered ring (e.g., C3-C8 cycloalkyl, C5-C8 cycloalkenyl, or NR 7 In one embodiment, R 1 and R 2 together with the atom to which they are attached form cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, pyrrolidinyl, or piperidinyl, and the nitrogen atom in the pyrrolidinyl or piperidinyl group is NR 7 In an embodiment, R 7 is alkylsulfonyl-SO2R 10c (e.g., -SO2Me), or acyl-COR 8 (e.g., acetyl). In embodiments, R 5 is phenyl or pyridyl. In embodiments, R 5 is unsubstituted. In embodiments, R 5 is substituted (e.g., phenyl substituted with 1, 2, 3, 4, or 5 substituents, or pyridyl substituted with 1, 2, 3, or 4 substituents). In embodiments, the substituents are -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0009] In embodiments, the compound is according to any formula described herein, or a pharmaceutically acceptable salt thereof. In embodiments, the compound is any compound described herein, or a pharmaceutically acceptable salt thereof (e.g., a compound described in any of Tables 1-39 described herein, or a pharmaceutically acceptable salt thereof). In embodiments, the compound is a compound described in any of Tables 34-39, or a pharmaceutically acceptable salt thereof.

[0010] In embodiments, the compound has the S-configuration at the nitrogen-substituted carbon of the lactam. In embodiments, the compound has the R-configuration at the nitrogen-substituted carbon of the lactam.

[0011] The present invention provides It further relates to a composition comprising an effective amount of one or more compounds according to the invention and an excipient.

[0012] The present invention also relates to a method for treating or preventing a disease associated with dysregulated 5-hydroxytryptamine receptor 7 activity, including, for example, circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders, attention-deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcoholism, breast cancer, liver fibrosis, chronic liver damage, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury, the method comprising administering to a subject an effective amount of a compound or composition according to the present invention.

[0013] The present invention further relates to a method for treating or preventing a disease associated with dysregulated 5-hydroxytryptamine receptor 7 activity, including, for example, circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders, attention-deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcoholism, breast cancer, liver fibrosis, chronic liver damage, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury, the method comprising administering to a subject a composition comprising an effective amount of one or more compounds according to the present invention and an excipient.

[0014] The present invention also relates to a method for treating or preventing diseases or symptoms associated with circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders, attention-deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcoholism, breast cancer, liver fibrosis, chronic liver damage, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury, as well as diseases associated with dysregulated 5-hydroxytryptamine receptor 7 activity. The method comprises administering an effective amount of a compound or composition according to the present invention to a subject.

[0015] The present invention further relates to a method for treating or preventing a disease or condition associated with circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders, attention-deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enterocolitis, epilepsy, seizure disorders, drug addiction, alcoholism, breast cancer, liver fibrosis, chronic liver damage, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury, as well as diseases involving dysregulation of 5-hydroxytryptamine receptor 7 activity, the method comprising administering to a subject a composition comprising an effective amount of one or more compounds according to the present invention and an excipient.

[0016] The present invention also relates to a method for treating or preventing a disease or condition associated with dysregulated 5-hydroxytryptamine receptor 7 activity, comprising administering to a subject an effective amount of a compound or composition according to the present invention.

[0017] The present invention further relates to a method for treating or preventing a disease or condition associated with dysregulation of 5-hydroxytryptamine receptor 7 activity, the method comprising administering to a subject a composition comprising an effective amount of one or more compounds according to the present invention and an excipient.

[0018] The present invention further relates to a process for preparing the 5-hydroxytryptamine receptor 7 activity modulators of the present invention.

[0019] In embodiments, the disease or condition is inflammatory bowel disease (IBD).

[0020] These and other objects, features, and advantages will become apparent to those skilled in the art upon reading the following detailed description and the appended claims. All percentages, ratios, and proportions herein are by weight unless otherwise specified. All temperatures are in degrees Celsius (°C) unless otherwise specified. All documents cited are, in relevant part, incorporated herein by reference, but the citation of any document should not be construed as an admission that it is prior art relevant to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0021] Evidence exists suggesting a role for the 5-HT7 receptor in a variety of medical disorders. Modulators of 5-HT7 receptor activity are likely to have beneficial effects on patients suffering from these disorders. Disorders in which 5-HT7 dysregulation plays a role and in which modulation of 5-HT7 receptor activity by therapeutic agents may be a viable approach for therapeutic relief include circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, and migraine (Vanhoenacker, P. et al., Trends in Pharmacology, 2014). Sciences, 2000, 21, 2, 70-77), neuropathic pain, peripheral pain, allodynia (EP1875899), thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders (WO2010 / 0197700), attention deficit hyperactivity disorder (ADHD) (WO2010 / 0069390), anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder (WO2004 / 0229874), inflammatory bowel disease (IBD), enteritis (WO2012 / 058769, Khan, WI, et. al. Journal of Immunology, 2013, 190, 4795-4804), epilepsy, seizure disorders Research (2007) 75, 39), drug addiction, alcoholism (Hauser, SR et. al. Frontiers in Neuroscience, 2015, 8, 1-9), breast cancer (Gautam, J. Molecular Cancer, 2016, 15, 75, 1-14, Gautam, J. Breast Cancer Research and Treatment, 2017, 161, 29-40), liver fibrosis, chronic liver damage (Halici, Z. International Immunopharmacology, 2017, 43, 227-235), hepatocellular carcinoma (Bian, Z. Molecular Oncology, 2016, 10, 195-212), small intestinal neuroendocrine tumors (Modlin, IMCarcancer Science, 2013, 104, 7, 844) -855), and lung injury (Halici, Z. Immunology, 2013, 1271-1283).

[0022] There is a long-felt need for novel 5-HT7 modulators that will provide therapeutic relief to patients suffering from diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity. The present invention addresses the need to identify novel 5-HT7 modulators that can treat diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity. The present invention addresses the need to develop novel therapeutic agents for the treatment and prevention of circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disabilities, memory disorders, hippocampal signaling disorders, sleep disorders, attention deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcoholism, breast cancer, liver fibrosis, chronic liver damage, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury.

[0023] The 5-hydroxytryptamine receptor 7 activity modulators of the present invention can treat and prevent diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity, such as circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disorders, memory disorders, hippocampal signal transduction disorders, sleep disorders, attention-deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcoholism, breast cancer, liver fibrosis, chronic liver damage, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury. The 5-hydroxytryptamine receptor 7 has been shown to play a role in many medical disorders, and therefore, modulators of 5-HT7 receptor activity are likely to have beneficial effects on patients suffering from these disorders. Disorders for which modulation of 5-HT7 receptor activity by therapeutic agents may be a viable approach for therapeutic relief include circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, and migraine (Vanhoenacker, P. et al., Trends in Pharmacology, 2014). Sciences, 2000, 21, 2, 70-77), neuropathic pain, peripheral pain, allodynia (EP1875899), thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders (WO2010 / 0197700), attention deficit hyperactivity disorder (ADHD) (WO2010 / 0069390), anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder (WO2004 / 0229874), inflammatory bowel disease (IBD), enteritis (WO2012 / 058769), epilepsy, seizure disorders (Epilepsy Research (2007) 75, 39), drug dependence, alcohol dependence (Hauser, SR et. al. Frontiers in Neuroscience, 2015, 8, 1-9), breast cancer (Gautam, J. Molecular Cancer, 2016, 15, 75, 1-14; Gautam, J. Breast Cancer Research and Treatment, 2017, 161, 29-40), liver fibrosis, chronic liver injury (Halici, Z. International Immunopharmacology, 2017, 43, 227-235), hepatocellular carcinoma (Bian, Z. Molecular Oncology, 2016, 10, 195-212), small intestinal neuroendocrine tumors (Modlin, I. M. Cancer Science, 2013, 104, 7, 844-855), and lung injury (Halici, Z. Immunology, 2013, 1271-1283).

[0024] Without wishing to be limited by theory, it is believed that the 5-hydroxytryptamine receptor 7 activity modulators of the present invention can improve, ameliorate, or control diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity, including, but not limited to, circadian rhythm disorders, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders, attention-deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphoric disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcoholism, breast cancer, liver fibrosis, chronic liver damage, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury.

[0025] In embodiments, the disease is depression, schizophrenia, an anxiety disorder, or a bipolar disorder. In embodiments, the disease is depression. In embodiments, the disease is schizophrenia. In embodiments, the disease is an anxiety disorder. In embodiments, the disease is a bipolar disorder.

[0026] In embodiments, the disease is attention deficit / hyperactivity disorder.

[0027] In embodiments, the disease is avoidant personality disorder.

[0028] In embodiments, the disease is seasonal affective disorder.

[0029] In embodiments, the disease is a circadian rhythm disorder or a hippocampal signaling disorder. In embodiments, the disease is a circadian rhythm disorder. In embodiments, the disease is a hippocampal signaling disorder.

[0030] In embodiments, the disease is neurogenic inflammation.

[0031] In embodiments, the disorder is neuropathic pain, peripheral pain, or allodynia. In embodiments, the disorder is neuropathic pain. In embodiments, the disorder is peripheral pain. In embodiments, the disorder is allodynia.

[0032] In an embodiment, the disease is migraine.

[0033] In embodiments, the disease is epilepsy or a seizure disorder. In embodiments, the disease is epilepsy. In embodiments, the disease is a seizure disorder.

[0034] In embodiments, the disorder is a learning disorder or a memory disorder. In embodiments, the disorder is a learning disorder. In embodiments, the disorder is a memory disorder.

[0035] In embodiments, the disease is an eating disorder.

[0036] In embodiments, the disease is drug or alcohol addiction.

[0037] In an embodiment, the disease is a sleep disorder.

[0038] In embodiments, the disease is hypertension or peripheral vascular disease. In embodiments, the disease is hypertension. In embodiments, the disease is peripheral vascular disease.

[0039] In embodiments, the disease is a thermoregulatory disorder.

[0040] In an embodiment, the disease is premature ejaculation.

[0041] In embodiments, the disease is premenstrual syndrome or premenstrual dysphoric disorder. In embodiments, the disease is premenstrual syndrome. In embodiments, the disease is premenstrual dysphoric disorder.

[0042] In embodiments, the disease is inflammatory bowel disease (IBD) or enteritis. In embodiments, the disease is inflammatory bowel disease (IBD). In embodiments, the disease is enteritis.

[0043] In an embodiment, the disease is breast cancer.

[0044] In embodiments, the disease is liver fibrosis, chronic liver damage, or hepatocellular carcinoma. In embodiments, the disease is liver fibrosis. In embodiments, the disease is chronic liver damage. In embodiments, the disease is hepatocellular carcinoma.

[0045] In embodiments, the disease is a small intestinal neuroendocrine tumor.

[0046] In embodiments, the disease is lung injury.

[0047] In embodiments, the disease is inflammatory bowel disease (IBD).

[0048] In embodiments, the compounds described herein are selective modulators of serotonin 5HT7 receptors.In embodiments, the compounds described herein can bind serotonin 5HT7 receptors more strongly than other targets (for example, other serotonin receptors).In embodiments, the compounds can selectively bind serotonin 5HT7 receptors in specific tissues or organs.

[0049] In embodiments, the compounds described herein may have particularly advantageous properties for effective therapy (e.g., of any of the diseases or conditions described herein). For example, CN In the treatment of CNS or psychiatric disorders, the compounds described herein can advantageously exhibit effective blood-brain barrier permeability. Alternatively, in the treatment of non-CNS or non-psychiatric disorders, the compounds described herein do not have high blood-brain barrier permeability (e.g., reduce off-target effects).Without being bound by theory, the molecular elements of the compound can be an effective strategy for achieving desired biological targeting.

[0050] For example, the compounds described herein can selectively bind to serotonin 5HT7 receptors in the intestine of a subject. Thus, the compounds can be used to treat or prevent inflammatory bowel disease (IBD) or intestinal inflammation.

[0051] Throughout this specification, when a composition is described as having, comprising, or including particular components, or a process is described as having, comprising, or including particular process steps, it is contemplated that the compositions of the present teachings also consist essentially of or consist of the recited components, and that the processes of the present teachings also consist essentially of or consist of the recited process steps.

[0052] Whenever an element or component is described herein as being included in and / or selected from a recited list of elements or components, it is understood that the element or component can be any one of the recited elements or components, or can be selected from a group consisting of two or more of the recited elements or components.

[0053] The use of the singular herein includes the plural (and vice versa) unless otherwise specified. Furthermore, when the term "about" is used before a quantitative value, the present teachings also include the particular quantitative value itself, unless otherwise specified.

[0054] It should be understood that the order of steps or order for performing certain actions is immaterial so long as the present teachings remain operable. Moreover, two or more steps or actions may be conducted simultaneously.

[0055] As used herein, the term "halogen" means chlorine, bromine, fluorine, and iodine.

[0056] As used herein, unless otherwise specified, "alkyl" and / or "aliphatic," whether used alone or as part of another group, refer to straight and branched carbon chains having 1 to 20 carbon atoms, or any number within this range, e.g., 1 to 6 carbon atoms or 1 to 4 carbon atoms. 1-6) independently refers to the number of carbon atoms in the alkyl moiety or to the alkyl portion of a larger alkyl-containing substituent. Non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, and the like. Alkyl groups can be optionally substituted. Non-limiting examples of substituted alkyl groups include hydroxymethyl, chloromethyl, trifluoromethyl, aminomethyl, 1-chloroethyl, 2-hydroxyethyl, 1,2-difluoroethyl, 3-carboxypropyl, and the like. (C 1-6 In substituents having multiple alkyl groups, such as alkyl)2amino, the alkyl groups may be the same or different.

[0057] As used herein, the terms "alkenyl" and "alkynyl" groups, whether used alone or as part of another group, refer to straight and branched carbon chains having two or more carbon atoms, preferably from 2 to 20 carbon atoms, wherein an alkenyl chain has at least one double bond in the chain and an alkynyl chain has at least one The alkenyl and alkynyl groups have a triple bond of 1 to 3. The alkenyl and alkynyl groups can be optionally substituted. Non-limiting examples of alkenyl groups include ethenyl, 3-propenyl, 1-propenyl (also known as 2-methylethenyl), isopropenyl (also known as 2-methylethen-2-yl), buten-4-yl, and the like. Non-limiting examples of substituted alkenyl groups include 2-chloroethenyl (also known as 2-chlorovinyl), 4-hydroxybuten-1-yl, 7-hydroxy-7-methyloct-4-en-2-yl, 7-hydroxy-7-methyloct-3,5-dien-2-yl, and the like. Non-limiting examples of alkynyl groups include ethynyl, prop-2-ynyl (also known as propargyl), propyn-1-yl, and 2-methyl-hex-4-yn-1-yl. Non-limiting examples of substituted alkynyl groups include 5-hydroxy-5-methylhex-3-ynyl, 6-hydroxy-6-methylhept-3-yn-2-yl, 5-hydroxy-5-ethylhept-3-ynyl, and the like.

[0058] As used herein, "cycloalkyl," whether used alone or as part of another group, refers to a non-aromatic carbon-containing ring, including, for example, cyclized alkyl, alkenyl, and alkynyl groups having 3 to 14 ring carbon atoms, preferably 3 to 7 or 3 to 6 ring carbon atoms, or 3 to 4 ring carbon atoms, and optionally containing one or more (e.g., 1, 2, or 3) double or triple bonds. Cycloalkyl groups can be monocyclic (e.g., cyclohexyl) or polycyclic (e.g., containing fused, bridged, and / or spiro ring systems), with carbon atoms located inside or outside the ring system. Any suitable ring position of a cycloalkyl group can be covalently linked to the defined chemical structure. Cycloalkyl rings can be optionally substituted. Non-limiting examples of cycloalkyl groups include cyclopropyl, 2-methyl-cyclopropyl, cyclopropenyl, cyclobutyl, 2,3-dihydroxycyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclopentadienyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctanyl, decalinyl, 2,5-dimethylcyclopentyl, 3,5-dichlorocyclohexyl, 4-hydroxycyclohexyl, 3,3,5-trimethylcyclohex-1-yl, octahydropentalenyl, octahydro-1H-indenyl, 3a,4,5,6,7,7a-hexahydro-3H-inden-4-yl, decahydroazulenyl, bicyclo[6.2.0]decanyl, decahydronaphthalenyl, and dodecahydro-1H-fluorenyl. The term "cycloalkyl" also includes carbocyclic rings that are bicyclic hydrocarbon rings, non-limiting examples of which include bicyclo-[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, 1,3-dimethyl[2.2.1]heptan-2-yl, bicyclo[2.2.2]octanyl, and bicyclo[3.3.3]undecanyl.

[0059] "Haloalkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms substituted with one or more halogens. Haloalkyl groups include perhaloalkyl groups in which all hydrogen atoms of the alkyl group are replaced with halogens (e.g., -CF3, -CF2CF3). Haloalkyl groups may be optionally substituted with one or more substituents in addition to halogens. Examples of haloalkyl groups include, but are not limited to, fluoromethyl, dichloroethyl, trifluoromethyl, trichloromethyl, pentafluoroethyl, and pentachloroethyl groups.

[0060] The term "alkoxy" refers to the group -O-alkyl, where alkyl is as defined above. The alkoxy group may be optionally substituted. The term C3-C6 cyclic alkoxy refers to a ring containing 3 to 6 carbon atoms and at least one oxygen atom (e.g., tetrahydrofuran, tetrahydro-2H-pyran). The C3-C6 cyclic alkoxy group may be optionally substituted.

[0061] The term "haloalkoxy" refers to the group -O haloalkyl, where haloalkyl is as defined above. Examples of haloalkoxy groups include, but are not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, and pentafluoroethoxyl.

[0062] The term "aryl," used alone or as part of another group, is defined herein as an unsaturated aromatic monocyclic ring of 6 carbon members or an unsaturated aromatic polycyclic ring of 10 to 14 carbon members. The aryl ring may be, for example, a phenyl ring or a naphthyl ring, each optionally substituted with one or more moieties capable of replacing one or more hydrogen atoms. Non-limiting examples of aryl groups include phenyl, naphthylene-1-yl, naphthylene-2-yl, 4-fluorophenyl, 2-hydroxyphenyl, 3-methylphenyl, 2-amino-4-fluorophenyl, 2-(N,N-diethylamino)phenyl, 2-cyanophenyl, 2,6-di-tert-butylphenyl, 3-methoxyphenyl, 8-hydroxynaphthylene-2-yl, 4,5-dimethoxynaphthylene-1-yl, and 6-cyanonaphthylene-1-yl. Aryl groups also include, for example, phenyl or naphthyl rings fused with one or more saturated or partially saturated carbocyclic rings (e.g., bicyclo[4.2.0]octa-1,3,5-trienyl, indanyl), which may be substituted at one or more carbon atoms of the aromatic and / or saturated or partially saturated rings.

[0063] The term "arylalkyl" or "aralkyl" refers to the group -alkyl-aryl, where the alkyl and aryl groups are as defined herein. The aralkyl groups of the present invention are optionally substituted. Examples of arylalkyl groups include, for example, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 2-phenylpropyl, fluorenylmethyl, and the like.

[0064] The terms "heterocyclic" and / or "heterocycle" and / or "heterosilyl," whether used alone or as part of another group, are defined herein as one or more rings having 3 to 20 atoms, wherein at least one atom in at least one ring is a heteroatom selected from nitrogen (N), oxygen (O), or sulfur (S), and further, the heteroatom-containing ring is non-aromatic. In heterocyclic groups containing two or more fused rings, the non-heteroatom-bearing ring can be aryl (e.g., indolinyl, tetrahydroquinolinyl, chromanyl). Exemplary heterocyclic groups have 3 to 14 ring atoms, 1 to 5 of which are heteroatoms independently selected from nitrogen (N), oxygen (O), or sulfur (S). One or more N or S atoms in a heterocyclic group can be oxidized. A heterocyclic group can be optionally substituted.

[0065] Non-limiting examples of heterocyclic units having a single ring include diazirinyl, aziridinyl, urazolyl, azetidinyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolidinyl, isothiazolyl, isothiazolinyl, oxathiozolidinonyl, oxazolidinonyl, hydantoinyl, tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperazinyl, piperidinyl, dihydropyranyl, tetrahydropyranyl, piperidin-2-onyl (valerolactam), 2,3,4,5-tetrahydro-1H-azepinyl, 2,3-dihydro-1H-indole, and 1,2,3,4-tetrahydro-quinoline. Non-limiting examples of heterocyclic units having two or more rings include hexahydro-1H-pyrrolidinyl, 3a,4,5,6,7a-hexahydro-1H-benzo[d]imidazolyl, 3a,4,5,6,7a-hexahydro-1H-indolyl, 1,2,3,4-tetrahydroquinolinyl, chromanyl, isochromanyl, indolinyl, isoindolinyl, and decahydro-1H-cycloocta[b]pyrrolyl.

[0066] The term "heteroaryl," whether used alone or as part of another group, is defined herein as one or more rings having 5 to 20 atoms, wherein at least one atom in at least one ring is a heteroatom selected from nitrogen (N), oxygen (O), or sulfur (S), and at least one ring containing a heteroatom is aromatic. In heteroaryl groups containing two or more fused rings, the non-heteroatom-bearing ring can be carbocyclic (e.g., 6,7-dihydro-5H-cyclopentapyrimidine) or aryl (e.g., benzofuranyl, benzothiophenyl, indolyl). Exemplary heteroaryl groups have 5 to 14 ring atoms and contain 1 to 5 ring heteroatoms independently selected from nitrogen (N), oxygen (O), or sulfur (S). One or more N or S atoms in a heteroaryl group can be oxidized. Heteroaryl groups can be substituted. Non-limiting examples of heteroaryl rings containing a single ring include 1,2,3,4-tetrazolyl, [1,2,3]triazolyl, [1,2,4]triazolyl, triazinyl, thiazolyl, 1H-imidazolyl, oxazolyl, furanyl, thiopheneyl, pyrimidinyl, 2-phenylpyrimidinyl, pyridinyl, 3-methylpyridinyl, and 4-dimethylaminopyridinyl. Non-limiting examples of heteroaryl rings containing two or more fused rings include benzofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, cinnolinyl, naphthyridinyl, phenanthridinyl, 7H-purinyl, 9H-purinyl, 6-amino-9H-purinyl, 5H-pyrrolo[3,2-d]pyrimidinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, pyr ... 1H-benzo[d]imidazol-2(3H)-onyl, 1H-benzo[d]imidazolyl, and isoquinolinyl.

[0067] One non-limiting example of the heteroaryl group is C1-C5 heteroaryl, which has 1 to 5 carbon ring atoms and at least one additional ring atom that is a heteroatom independently selected from nitrogen (N), oxygen (O), or sulfur (S) (preferably, 1 to 4 additional ring atoms that are heteroatoms). Examples of C1-C5 heteroaryl include, but are not limited to, triazinyl, thiazol-2-yl, thiazol-4-yl, imidazol-1-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, isoxazolin-5-yl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl.

[0068] Unless otherwise specified, two substituents taken together form a ring having a specified number of ring atoms (e.g., R 2 and R 3 together with the nitrogen (N) to which they are attached to form a ring having 3 to 7 ring members, the ring can have carbon atoms and, optionally, one or more (e.g., 1 to 3) additional heteroatoms independently selected from nitrogen (N), oxygen (O), or sulfur (S). The ring can be saturated or partially saturated and can be optionally substituted.

[0069] For purposes of this invention, fused ring units as well as spirocyclic rings, bicyclic rings, and the like, containing a single heteroatom are considered to belong to the ring group corresponding to the heteroatom-containing ring. For example, rings of the formula: [ka] is considered a heterocyclic unit for purposes of the present invention. [ka] For purposes of the present invention, 6,7-dihydro-5H-cyclopentapyrimidine having the formula: is considered a heteroaryl unit. When a fused ring unit contains heteroatoms in both the saturated ring and the aryl ring, the aryl ring will dominate and determine the type of category to which the ring is assigned. For example, [ka] is considered a heteroaryl unit for purposes of this invention.

[0070] When a term or any of its prefix roots appears in the name of a substituent, the name should be interpreted as including those limitations provided herein. For example, when the term "alkyl" or "aryl," or any of their prefix roots, appears in the name of a substituent (e.g., arylalkyl, alkylamino), the name should be interpreted as including those limitations set forth above for "alkyl" and "aryl."

[0071] The term "substituted" is used throughout this specification. The term "substituted" is defined herein as a moiety, whether acyclic or cyclic, having one or more hydrogen atoms replaced with a substituent or several (e.g., 1 to 10) substituents as defined below. Substituents can replace one or two hydrogen atoms of a single moiety at a time. Furthermore, these substituents can replace two hydrogen atoms on two adjacent carbons to form the substituent, new moiety, or unit. For example, substitution units requiring the replacement of a single hydrogen atom include halogen, hydroxyl, etc. Replacement of two hydrogen atoms includes carbonyl, oximino, etc. Replacement of two hydrogen atoms from adjacent carbon atoms includes epoxy, etc. The term "substituted" is used throughout this specification to indicate that a moiety can have one or more hydrogen atoms replaced by a substituent. When a moiety is described as "substituted," any number of hydrogen atoms can be replaced. For example, difluoromethyl is a substituted C1 alkyl, trifluoromethyl is a substituted C1 alkyl, 4-hydroxyphenyl is a substituted aromatic ring, (N,N-dimethyl-5-amino)octanyl is a substituted C8 alkyl, 3-guanidinopropyl is a substituted C3 alkyl, and 2-carboxypyridinyl is a substituted heteroaryl.

[0072] Variable groups as defined herein, for example, alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, aryloxy, aryl, heterocyclic, and heteroaryl groups as defined herein, whether used alone or as part of another group, can be optionally substituted. Optionally substituted groups are so designated.

[0073] Non-limiting examples of substituents that can be substituted for hydrogen atoms on a moiety include: halogen (chlorine (Cl), bromine (Br), fluorine (F), and iodine (I)), -CN, -NO2, oxo (=O), -OR 26 , -SR 26, -N(R 26 )2, -NR 26 C(O)R 2 6 , -SO2R 26 , -SO2OR 26 , -SO2N(R 26 )2, -C(O)R 26 , -C(O)OR 26 , -C(O)N(R 26 )2, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 2-8 Alkenyl, C 2-8 Alkynyl, C 3-14 cycloalkyl, aryl, heterocycle, or heteroaryl, and each of alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocycle, and heteroaryl is selected from halogen, —CN, —NO, oxo, and R 26 optionally substituted with 1 to 10 (e.g., 1 to 6 or 1 to 4) groups independently selected from 26 independently in each occurrence, hydrogen, -OR 27 , -SR 27 , -C(O)R 27 , -C(O)OR 27 , -C(O)N(R 27 )2, -SO2R 27 , -S(O)2OR 27 , -N(R 27 )2, -NR 27 C(O)R 27 , C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-8 Alkenyl, C 2-8 Alkynyl, cycloalkyl (e.g., C 3-6 cycloalkyl), aryl, heterocycle, or heteroaryl, or two R 26 units, together with the atom(s) to which they are attached, form an optionally substituted carbocyclic or heterocyclic ring, wherein the carbocyclic or heterocyclic ring has 3 to 7 ring atoms; R 27 independently in each occurrence: hydrogen, C 1-6Alkyl, C 1-6 Haloalkyl, C 2-8 Alkenyl, C 2-8 Alkynyl, cycloalkyl (e.g., C 3-6 cycloalkyl), aryl, heterocycle, or heteroaryl, or two R 27 The units, together with the atom(s) to which they are attached, form an optionally substituted carbocyclic or heterocyclic ring, wherein the carbocyclic or heterocyclic ring has from 3 to 7 ring atoms.

[0074] In some embodiments, the substituent is i)-OR 28 ;for example, -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3; ii)-C(O)R 28 ;for example, -COCH3, -COCH2CH3, -COCH2CH2CH3; iii)-C(O)OR 28 ;for example, -CO2CH3, -CO2CH2CH3, -CO2CH2CH2CH3; iv)-C(O)N(R 28 )2; e.g., -CONH2, -CONHCH3, -CON(CH3)2; v)-N(R 28 )2; for example, -NH2, -NHCH3, -N(CH3)2, -NH(CH2CH3); vi) halogens: -F, -Cl, -Br, and -I; vii)-CH e X g wherein X is a halogen, m is 0-2, and e+g=3; for example, —CH2F, —CHF2, —CF3, —CCl3, or —CBr3; viii)-SO2R 28 ;For example, -SO2H;-SO2CH3;-SO2C6H5; ix) C1-C6 straight chain, branched, or cyclic alkyl; x) cyano; xi) nitro; xii)N(R 28 )C(O)R 28 ; xiii) oxo(=O); xiv) heterocycles; and xv) heteroaryl; In the formula, each R 28 are independently hydrogen, optionally substituted C1-C6 straight chain or branched alkyl (e.g., optionally substituted C1-C4 straight chain or branched alkyl), or optionally substituted C3-C6 cycloalkyl (e.g., optionally substituted C3-C4 cycloalkyl), or two R 28 The units can, together, form a ring containing 3 to 7 ring atoms. In certain embodiments, each R 28 are independently hydrogen, C1-C6 straight or branched alkyl optionally substituted with halogen, or C3-C6 cycloalkyl, or C3-C6 cycloalkyl.

[0075] At various places in the present specification, substituents of compounds are disclosed in groups or in ranges. It is specifically intended that the description include each individual subbond of the members of such groups and ranges. For example, "C 1-6 The term "alkyl" is specifically intended to individually disclose C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6 alkyl.

[0076] For purposes of the present invention, the terms "compound," "analog," and "composition of matter" refer equally well to the 5-hydroxytryptamine receptor 7 activity modulators described herein, including all enantiomeric forms, diastereomeric forms, salts, etc., and these terms "compound," "analog," and "composition of matter" are used interchangeably throughout this specification.

[0077] The compounds described herein may contain asymmetric atoms (also called chiral centers), and some compounds may contain one or more asymmetric atoms or centers, thus giving rise to optical isomers (enantiomers) and diastereomers. The present teachings and compounds disclosed herein include such enantiomers and diastereomers, as well as racemic and resolved, enantiomerically pure R and S stereoisomers, as well as mixtures of other R and S stereoisomers and pharmaceutically acceptable salts thereof. Optical isomers can be obtained in pure form by standard procedures known to those skilled in the art, including, but not limited to, diastereomeric salt formation, kinetic resolution, and asymmetric synthesis. The present teachings also encompass cis and trans isomers of compounds containing alkenyl moieties (e.g., alkenes and imines). It is also understood that the present teachings encompass all possible positional isomers, and mixtures thereof, which can be obtained in pure form by standard separation procedures known to those skilled in the art, including, but not limited to, column chromatography, thin layer chromatography, and high performance liquid chromatography.

[0078] Pharmaceutically acceptable salts of the compounds of the present teachings can have an acidic moiety and can be formed using organic and inorganic bases.Depending on the number of acidic hydrogens available for deprotonation, both monoanionic and polyanionic salts are contemplated.Suitable salts formed using bases include metal salts, such as alkali metal salts or alkaline earth metal salts, for example, sodium salts, potassium salts, or magnesium salts; ammonia salts and organic amine salts, such as salts formed with morpholine, thiomorpholine, piperidine, pyrrolidine, mono-, di-, or tri-lower alkylamines (e.g., ethyl-tert-butylamine, diethylamine, diisopropylamine, triethylamine, or dimethylpropylamine), or mono-, di-, or tri-hydroxy-lower alkylamines (e.g., monoethanolamine, diethanolamine, or triethanolamine). Specific, non-limiting examples of inorganic bases include NaHCO3, Na2CO3, KHCO3, K2CO3, Cs2CO3, LiOH, NaOH, KOH, NaH2PO4, Na2HPO4, and Na3PO4. Internal salts can also be formed. Similarly, when the compounds disclosed herein contain a basic moiety, salts can be formed using organic and inorganic acids. For example, salts can be formed with the following acids: acetic acid, propionic acid, lactic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, tartaric acid, succinic acid, dichloroacetic acid, ethenesulfonic acid, formic acid, fumaric acid, gluconic acid, glutamic acid, hippuric acid, hydrobromic acid, hydrochloric acid, isethionic acid, lactic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, naphthalenesulfonic acid, nitric acid, and the like. , oxalic acid, pamoic acid, pantothenic acid, phosphoric acid, phthalic acid, propionic acid, succinic acid, sulfuric acid, tartaric acid, toluenesulfonic acid, and camphorsulfonic acid, as well as other known pharmaceutically acceptable acids.

[0079] When any variable occurs more than one time in any constituent or in any formula, its definition on each occurrence is independent of its definition at every other occurrence (e.g., N(R 9 )2, each R 9 (may be the same or different). Combinations of substituents and / or variables are permissible only if such combinations result in stable compounds.

[0080] As used herein, the terms "treat" and "treating" and "treatment" refer to partially or completely alleviating, suppressing, ameliorating, and / or relieving symptoms from which a patient is suspected to be suffering.

[0081] As used herein, "therapeutically effective" and "effective dose" refer to a substance or amount that elicits a desired biological activity or effect.

[0082] Unless otherwise specified, the terms "subject" or "patient" are used interchangeably and refer to mammals, such as human patients and non-human primates, as well as laboratory animals such as rabbits, rats, and mice, and other animals. Thus, as used herein, the term "subject" or "patient" refers to any mammalian patient or subject to which the compounds of the present invention can be administered. In exemplary embodiments of the present invention, to identify subject patients for treatment with the methods of the present invention, generally accepted screening methods are used to determine risk factors associated with the targeted or suspected disease or condition, or to determine the subject's existing disease or condition status. These screening methods include, for example, conventional workups to determine risk factors that may be associated with the targeted or suspected disease or condition. These and other routine methods allow clinicians to select patients in need of treatment using the methods and compounds of the present invention.

[0083] 5-Hydroxytryptamine receptor 7 activity modulators The present invention relates to a compound of formula (I), which is a novel 5-hydroxytryptamine receptor 7 (5-HT7) activity modulator: [ka] The present invention is directed to enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof, wherein: A, [ka] is selected from the group consisting of R 1 But hydrogen, C 1-6 Straight chain alkyl, C 3-7 branched alkyl; R 2 But hydrogen, C 1-6 Straight chain alkyl, C 3-7 branched alkyl Ruka, Or R 1 and R 2 together with the atoms to which they are attached form a ring having 5 to 7 ring atoms, optionally containing a double bond, or or R 1 and R 2 together with the atoms to which they are attached, form O, S, SO, SO2, and NR 7 forming a ring having 6 to 8 ring atoms containing a moiety selected from the group consisting of R 3 optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, and [ka] is selected from the group consisting of R 4optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, and [ka] is selected from the group consisting of R 5 optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, and [ka] is selected from the group consisting of R 6 is selected from the group consisting of optionally substituted phenyl, optionally substituted naphthylene-1-yl, optionally substituted naphthylene-2-yl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, and optionally substituted 4-pyridyl; R 7 is H, C1-6 straight chain alkyl, C3-7 branched alkyl, C3-7 cycloalkyl, optionally substituted phenyl, optionally substituted benzyl, COR 8 , CO2R 9 ,CONR 10a R 10b , SO2NR 10a R 10b , and SO2R 10c is selected from the group consisting of R 8 But H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 9 But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 10a But H, C1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 10b But H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 10c But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C1-6 straight-chain haloalkyl, C3-7 branched haloalkyl, -(CH2) q CN, -(CH2) q SO2R 11 , -(CH2) q OR 12 , [ka] is selected from the group consisting of R 11 But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 12 But C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 1a , R 1b , R 1c , R 1d , and R 1e independently in each occurrence: H, OH, NO2, halogen, CN, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6Straight chain haloalkoxy, -S(C 1-6 Straight chain alkyl), S(C 3-7 Branched alkyl), -S(C 3-7 cycloalkyl), COR 13 , CO2R 14 ,CONR 15a R 15b , SO2NR 15a R 15b , N.R. 16a R 16b , N.R. 16a COR 17 , N.R. 16a SO2R 18 , and N.R. 16a SO2NR 19a R 19b is selected from the group consisting of R 13 But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 14 but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 15a But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 15b But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 16a But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 16b But independently in each occurrence, H, C 1-6 Straight chain alkyl, C3-7 Branched alkyl, and C 3-7 cycloalkyl; R 17 But independently in each occurrence, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 18 but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 19a but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 19b but independently in each occurrence, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and and C 3-7 cycloalkyl; n is 1, 2, 3, or 4; m is 1, 2, or 3.

[0084] In an embodiment, A, [ka] and Each R 1 and R 2 But independently, C 1-6 Straight chain alkyl or C 3-7 branched alkyl or R 1 and R 2 form a 5- to 8-membered ring together with the atoms to which they are attached, The 5- to 8-membered ring is saturated or contains a carbon-carbon double bond and / or O, S, SO, SO2, or NR 7 and containing ring atoms which are Each R3 , R 4 , and R 5 is independently optionally substituted phenyl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, or optionally substituted 4-pyridyl; R 6 is independently optionally substituted phenyl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, or optionally substituted 4-pyridyl; R 7 However, independently, H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, COR 8 , or SO2R 10c and R 8 But H, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 10c But C 1-6 Straight chain alkyl or C 3-7 is a branched alkyl; n is 1, 2, 3, or 4; m is 1, 2, or 3.

[0085] In embodiments, n is 1, 2, or 3. In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 3.

[0086] An embodiment of the present invention has formula (II): [ka] This includes compounds including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0087] In embodiments, the compound has formula (XLII): [ka] or a pharmaceutically acceptable salt thereof.

[0088] In embodiments, the compound has formula (XLIII): [ka] or a pharmaceutically acceptable salt thereof.

[0089] In embodiments, n is 1, 2, or 3. In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 3. In embodiments, n is 1 or 2.

[0090] In embodiments, R 1 and R 2 Each of the 1-6 In embodiments, R 1 and R 2 Each of R is ethyl. 1 and R 2 Each of is methyl.

[0091] In embodiments, R 1 and R 2 together with the atoms to which they are attached, form one carbon-carbon double bond and / or O, S, SO, SO2, and NR 7 and forming a 5- to 8-membered ring optionally containing ring atoms selected from the group consisting of:

[0092] In embodiments, R 1 and R 2 together with the atoms to which they are attached form a C3-C8 cycloalkyl or a C5-C8 cycloalkenyl.

[0093] In embodiments, R 1 and R 2are taken together with the atoms to which they are attached to form a C3-C8 cycloalkyl or C5-C8 cycloalkenyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, and cyclooctenyl. In embodiments, the C3-C8 cycloalkyl or C5-C8 cycloalkenyl is unsubstituted. In embodiments, the C3-C8 cycloalkyl or C5-C8 cycloalkenyl is substituted with 1, 2, 3, or 4 substituents (e.g., 1 or 2 substituents described herein). In embodiments, the substituent is oxo (=O), hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In embodiments, the substituents are selected from -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0094] In embodiments, the compound has a structure according to formula (XXXXIIIa): [ka] or and pharmaceutically acceptable salts thereof, [ka] represents a single or double bond.

[0095] In an embodiment, [ka] represents a single bond.

[0096] In an embodiment, [ka] represents a double bond.

[0097] In embodiments, the nitrogen-substituted lactam stereocenter has the R configuration.

[0098] In embodiments, the nitrogen-substituted lactam stereocenter has the S configuration.

[0099] In embodiments, R 1 and R 2 together with the atoms to which they are attached, form NR 7 In embodiments, the 5-8 membered ring is not further substituted. In embodiments, the 5-8 membered ring further comprises 1, 2, 3, or 4 substituents (e.g., 1 or 2 substituents described herein). In embodiments, the substituents are oxo (=O), hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In embodiments, the substituents are selected from -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0100] In embodiments, R 1 and R 2 are taken together and the nitrogen atom is NR 7In embodiments, the pyrrolidinyl or piperidinyl group is not further substituted. In embodiments, the pyrrolidinyl or piperidinyl group further comprises one, two, three, or four substituents described herein.

[0101] In an embodiment, the compound has formula (XLIIIb) [ka] or a pharmaceutically acceptable salt thereof.

[0102] In an embodiment, the compound has formula (XLIV) [ka] or a pharmaceutically acceptable salt thereof.

[0103] In an embodiment, the compound has formula (XLV): [ka] or a pharmaceutically acceptable salt thereof.

[0104] In embodiments, n is 1, 2, or 3. In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 3. In embodiments, n is 1 or 2.

[0105] In embodiments, R 7 is COR 8 and R 8 is a C1-6 straight chain alkyl.

[0106] In embodiments, R 7 is acetyl.

[0107] In embodiments, R 7 is SO2R 10c and R 10c is a C1-6 straight chain alkyl.

[0108] In embodiments, R 10c is methyl (i.e., R 7 is SO2Me).

[0109] In embodiments, R 3 is unsubstituted phenyl.

[0110] In embodiments, R 3 is substituted phenyl. In embodiments, R 3 is phenyl substituted with 1, 2, 3, 4, or 5 substituents (e.g., phenyl substituted with 1 or 2 substituents as described herein). In embodiments, the substituents are hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In an embodiment, the substituents are selected from the group consisting of -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0111] In embodiments, R 3 is selected from the group consisting of hydroxylphenyl, fluorophenyl, chlorophenyl, bromophenyl, cyanophenyl, tolyl, methoxylphenyl, difluorophenyl, dichlorophenyl, chloro-fluorophenyl, dimethylphenyl, trifluoromethylphenyl, di(trifluoromethyl)phenyl.

[0112] In embodiments, R 3 are 4-hydroxyphenyl, 3-fluorophenyl, and 4-fluorophenyl. and 4-methyl-2-morpholinophenyl, 4-methyl-3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 4-fluoro-3-chlorophenyl, 4-cyanophenyl, 2-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-isopropylphenyl, 4-trifluoromethylphenyl, 2-morpholinophenyl, and 4-methyl-2-morpholinophenyl.

[0113] In embodiments, R 3 is 2-pyridyl. In embodiments, R 3 is 3-pyridyl. In embodiments, R 3 is 4-pyridyl. In embodiments, the pyridyl is unsubstituted. In embodiments, the pyridyl is substituted with 1, 2, 3, or 4 substituents (e.g., pyridyl substituted with 1 or 2 substituents as described herein). In embodiments, the substituents are hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In an embodiment, the substituents are selected from the group consisting of -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0114] An embodiment of the present invention has the formula (IIa): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , and R 20e at least three of are hydrogen.

[0115] An embodiment of the present invention has the formula (IIb): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0116] An embodiment of the present invention has the formula (IIc): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2is 1 or 2.

[0117] An embodiment of the present invention has the formula (IId): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0118] An embodiment of the present invention has the formula (IId-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0119] An embodiment of the present invention has the formula (IId-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0120] An embodiment of the present invention has the formula (IId-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0121] An embodiment of the present invention has the formula (IId-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0122] An embodiment of the present invention has the formula (IId-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0123] An embodiment of the present invention has the formula (IIe): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20d are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least three of are hydrogen.

[0124] An embodiment of the present invention has the formula (IIf): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0125] An embodiment of the present invention has the formula (IIg): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0126] An embodiment of the present invention has the formula (IIh): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0127] An embodiment of the present invention has the formula (IIh-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0128] An embodiment of the present invention has the formula (IIh-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0129] An embodiment of the present invention has the formula (IIh-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2is 1 or 2.

[0130] An embodiment of the present invention has the formula (IIh-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0131] An embodiment of the present invention has the formula (IIh-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0132] An embodiment of the present invention has the formula (IIi): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20e at least two of are hydrogen.

[0133] An embodiment of the present invention has the formula (IIj): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0134] An embodiment of the present invention has the formula (IIk): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0135] An embodiment of the present invention has the formula (IIL): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0136] An embodiment of the present invention has the formula (IIL-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0137] An embodiment of the present invention has the formula (IIL-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0138] An embodiment of the present invention has the formula (IIL-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0139] An embodiment of the present invention has the formula (IIL-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0140] An embodiment of the present invention has the formula (IIL-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0141] An embodiment of the present invention has the formula (IIm): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20cd , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least three of are hydrogen.

[0142] An embodiment of the present invention has the formula (IIn): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0143] An embodiment of the present invention has the formula (IIo): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0144] An embodiment of the present invention has the formula (IIp): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0145] An embodiment of the present invention has the formula (IIp-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0146] An embodiment of the present invention has the formula (IIp-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0147] An embodiment of the present invention has the formula (IIp-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0148] An embodiment of the present invention has the formula (IIp-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0149] An embodiment of the present invention has the formula (IIp-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0150] An embodiment of the present invention has the formula (IIq): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0151] An embodiment of the present invention has the formula (IIr): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0152] An embodiment of the present invention has the formula (IIs): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0153] An embodiment of the present invention has the formula (IIt): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0154] An embodiment of the present invention has the formula (IIt-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0155] An embodiment of the present invention has the formula (IIt-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0156] An embodiment of the present invention has the formula (IIt-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0157] An embodiment of the present invention has the formula (IIt-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q2 is 1 or 2.

[0158] An embodiment of the present invention has the formula (IIt-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0159] An embodiment of the present invention has the formula (IIu): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d, R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0160] An embodiment of the present invention has the formula (IIv): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0161] An embodiment of the present invention has the formula (IIw): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0162] An embodiment of the present invention has the formula (IIx): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0163] An embodiment of the present invention has the formula (IIx-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0164] An embodiment of the present invention has the formula (IIx-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0165] An embodiment of the present invention has the formula (IIx-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0166] An embodiment of the present invention has the formula (IIx-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0167] An embodiment of the present invention has the formula (IIx-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0168] An embodiment of the present invention has formula (III): [ka] This includes compounds including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0169] An embodiment of the present invention has the formula (IIIa): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , and R 20e at least three of are hydrogen.

[0170] An embodiment of the present invention has the formula (IIIb): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0171] An embodiment of the present invention has the formula (IIIc): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0172] An embodiment of the present invention has the formula (IIId): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0173] An embodiment of the present invention has the formula (IIId-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0174] An embodiment of the present invention has the formula (IIId-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0175] An embodiment of the present invention has the formula (IIId-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0176] An embodiment of the present invention has the formula (IIId-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0177] An embodiment of the present invention has the formula (IIId-5): [ka] Hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts thereof, and and complexes, wherein Q 1 is 1 or 2, Q 2 is 1 or 2.

[0178] An embodiment of the present invention has the formula (IIIe): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20d are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0179] An embodiment of the present invention has the formula (IIIf): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0180] An embodiment of the present invention has the formula (IIIg): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0181] An embodiment of the present invention has the formula (IIIh): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0182] An embodiment of the present invention has the formula (IIIh-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0183] An embodiment of the present invention has the formula (IIIh-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0184] An embodiment of the present invention has the formula (IIIh-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0185] An embodiment of the present invention has the formula (IIIh-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0186] An embodiment of the present invention has the formula (IIIh-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0187] An embodiment of the present invention has the formula (IIIi): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20eat least two of are hydrogen.

[0188] An embodiment of the present invention has the formula (IIIj): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0189] An embodiment of the present invention has the formula (IIIk): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0190] An embodiment of the present invention has the formula (IIIL): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0191] An embodiment of the present invention has the formula (IIIL-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0192] An embodiment of the present invention has the formula (IIIL-2): [ka] Hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts thereof, and and complexes, wherein Q 1 is 1 or 2, Q 2 is 1 or 2.

[0193] An embodiment of the present invention has the formula (IIIL-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0194] An embodiment of the present invention has the formula (IIIL-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0195] An embodiment of the present invention has the formula (IIIL-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0196] An embodiment of the present invention has the formula (IIIm): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24, C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0197] An embodiment of the present invention has the formula (IIIn): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0198] An embodiment of the present invention has the formula (IIIo): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0199] An embodiment of the present invention has the formula (IIIp): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0200] An embodiment of the present invention has the formula (IIIp-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1is 1 or 2, Q 2 is 1 or 2.

[0201] An embodiment of the present invention has the formula (IIIp-2): [ka] Hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts thereof, and and complexes, wherein Q 1 is 1 or 2, Q 2 is 1 or 2.

[0202] An embodiment of the present invention has the formula (IIIp-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0203] An embodiment of the present invention has the formula (IIIp-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0204] An embodiment of the present invention has the formula (IIIp-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0205] An embodiment of the present invention has the formula (IIIq): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0206] An embodiment of the present invention has the formula (IIIr): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0207] An embodiment of the present invention has the formula (IIIs): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0208] An embodiment of the present invention has the formula (IIIt): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0209] An embodiment of the present invention has the formula (IIIt-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1is 1 or 2, Q 2 is 1 or 2.

[0210] An embodiment of the present invention has the formula (IIIt-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0211] An embodiment of the present invention has the formula (IIIt-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0212] An embodiment of the present invention has the formula (IIIt-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0213] An embodiment of the present invention has the formula (IIIt-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0214] An embodiment of the present invention has the formula (IIIu): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0215] An embodiment of the present invention has the formula (IIIv): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0216] An embodiment of the present invention has the formula (IIIw): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0217] An embodiment of the present invention has the formula (IIIx): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0218] An embodiment of the present invention has the formula (IIIx-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1is 1 or 2, Q 2 is 1 or 2.

[0219] An embodiment of the present invention has the formula (IIIx-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0220] An embodiment of the present invention has the formula (IIIx-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0221] An embodiment of the present invention has the formula (IIIx-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0222] An embodiment of the present invention has the formula (IIIx-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0223] An embodiment of the present invention has formula (IV): [ka] This includes compounds including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0224] In embodiments, the compound has a structure according to formula (XLVII): [ka] , or a pharmaceutically acceptable salt thereof.

[0225] In embodiments, the compound has a structure according to formula (XLVII): [ka] or a pharmaceutically acceptable salt thereof.

[0226] In embodiments, n is 1, 2, or 3. In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 1 or 2.

[0227] In embodiments, R 1 and R 2 Each of the 1-6 In embodiments, R 1 and R 2 Each of R is ethyl. 1 and R 2 Each of is methyl.

[0228] In embodiments, R1 and R 2 together with the atoms to which they are attached, form one carbon-carbon double bond and / or O, S, SO, SO2, and NR 7 and forming a 5- to 8-membered ring optionally containing ring atoms selected from the group consisting of:

[0229] In embodiments, R 1 and R 2 together with the atoms to which they are attached form a C3-C8 cycloalkyl or a C5-C8 cycloalkenyl.

[0230] In embodiments, R 1 and R 2 are taken together with the atoms to which they are attached to form a C3-C8 cycloalkyl or C5-C8 cycloalkenyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, and cyclooctenyl. In embodiments, the C3-C8 cycloalkyl or C5-C8 cycloalkenyl is unsubstituted. In embodiments, the C3-C8 cycloalkyl or C5-C8 cycloalkenyl is substituted with 1, 2, 3, or 4 substituents (e.g., 1 or 2 substituents described herein). In embodiments, the substituent is oxo (=O), hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In embodiments, the substituents are selected from -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0231] In embodiments, R 1 and R 2 together with the atoms to which they are attached, form NR 7 In embodiments, the 5-8 membered ring is not further substituted. In embodiments, the 5-8 membered ring further comprises 1, 2, 3, or 4 substituents (e.g., 1 or 2 substituents described herein). In embodiments, the substituents are oxo (=O), hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In embodiments, the substituents are selected from -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0232] In embodiments, R 1 and R 2 are taken together and the nitrogen atom is NR 7 In embodiments, the pyrrolidinyl or piperidinyl group is The group is not further substituted. In embodiments, the pyrrolidinyl or piperidinyl group further comprises 1, 2, 3, or 4 substituents described herein.

[0233] In embodiments, R 7 is COR 8 and R 8 is a C1-6 straight chain alkyl.

[0234] In embodiments, R 7 is acetyl.

[0235] In embodiments, R 7 is SO2R 10c and R 10c is a C1-6 straight chain alkyl.

[0236] In embodiments, R 10c is methyl (i.e., R 7 is SO2Me).

[0237] In embodiments, R 4 is phenyl.

[0238] In embodiments, R 4 is substituted phenyl. In embodiments, R 4 is phenyl substituted with 1, 2, 3, 4, or 5 substituents (e.g., phenyl substituted with 1 or 2 substituents as described herein). In embodiments, the substituents are hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In an embodiment, the substituents are selected from the group consisting of -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0239] In embodiments, R 4 is selected from the group consisting of hydroxylphenyl, fluorophenyl, chlorophenyl, bromophenyl, cyanophenyl, tolyl, methoxylphenyl, difluorophenyl, dichlorophenyl, chloro-fluorophenyl, dimethylphenyl, trifluoromethylphenyl, di(trifluoromethyl)phenyl.

[0240] In embodiments, R4 is selected from the group consisting of 4-hydroxyphenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 4-fluoro-3-chlorophenyl, 4-cyanophenyl, 2-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-isopropylphenyl, 4-trifluoromethylphenyl, 2-morpholinophenyl, and 4-methyl-2-morpholinophenyl.

[0241] In embodiments, R 4 is pyridyl. In embodiments, R 4 is 2-pyridyl. In embodiments, R 4 is 3-pyridyl. In embodiments, R 4 is 4-pyridyl. In embodiments, the pyridyl is unsubstituted. In embodiments, the pyridyl is substituted with 1, 2, 3, or 4 substituents (e.g., pyridyl substituted with 1 or 2 substituents as described herein). In embodiments, the substituents are hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In an embodiment, the substituents are selected from the group consisting of -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0242] An embodiment of the present invention has formula (IVa): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , and R 20e at least three of are hydrogen.

[0243] An embodiment of the present invention has formula (IVb): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0244] An embodiment of the present invention has formula (IVc): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0245] An embodiment of the present invention has the formula (IVd): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0246] An embodiment of the present invention has the formula (IVd-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0247] An embodiment of the present invention has the formula (IVd-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0248] An embodiment of the present invention has the formula (IVd-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0249] An embodiment of the present invention has the formula (IVd-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0250] An embodiment of the present invention has the formula (IVd-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0251] An embodiment of the present invention has formula (IVe): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R20b , R 20c , and R 20d are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0252] An embodiment of the present invention has the formula (IVf): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0253] An embodiment of the present invention has the formula (IVg): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2is 1 or 2.

[0254] An embodiment of the present invention has the formula (IVh): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0255] An embodiment of the present invention has the formula (IVh-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0256] An embodiment of the present invention has the formula (IVh-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0257] An embodiment of the present invention has the formula (IVh-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0258] An embodiment of the present invention has the formula (IVh-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0259] An embodiment of the present invention has the formula (IVh-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0260] An embodiment of the present invention has formula (IVi): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20e at least two of are hydrogen.

[0261] An embodiment of the present invention has formula (IVj): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0262] An embodiment of the present invention has the formula (IVk): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0263] An embodiment of the present invention has the formula (IVL): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0264] An embodiment of the present invention has the formula (IVL-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0265] An embodiment of the present invention has the formula (IVL-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0266] An embodiment of the present invention has the formula (IVL-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0267] An embodiment of the present invention has the formula (IVL-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0268] An embodiment of the present invention has the formula (IVL-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0269] An embodiment of the present invention has the formula (IVm): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0270] An embodiment of the present invention has the formula (IVn): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0271] An embodiment of the present invention has the formula (IVo): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0272] An embodiment of the present invention has the formula (IVp): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0273] An embodiment of the present invention has the formula (IVp-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0274] An embodiment of the present invention has the formula (IVp-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0275] An embodiment of the present invention has the formula (IVp-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0276] An embodiment of the present invention has the formula (IVp-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0277] An embodiment of the present invention has the formula (IVp-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0278] An embodiment of the present invention has formula (IVq): [ka] Hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts thereof, and and complexes, wherein R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0279] An embodiment of the present invention has the formula (IVr): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0280] An embodiment of the present invention has formula (IVs): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0281] An embodiment of the present invention has the formula (IVt): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0282] An embodiment of the present invention has the formula (IVt-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0283] An embodiment of the present invention has formula (IVt-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0284] An embodiment of the present invention has the formula (IVt-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0285] An embodiment of the present invention has formula (IVt-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0286] An embodiment of the present invention has the formula (IVt-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0287] An embodiment of the present invention has the formula (IVu): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0288] An embodiment of the present invention has formula (IVv): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0289] An embodiment of the present invention has the formula (IVw): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0290] An embodiment of the present invention has the formula (IVx): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0291] An embodiment of the present invention has the formula (IVx-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0292] An embodiment of the present invention has formula (IVx-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0293] An embodiment of the present invention has the formula (IVx-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0294] An embodiment of the present invention has the formula (IVx-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0295] An embodiment of the present invention has the formula (IVx-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0296] An embodiment of the present invention has formula (V): [ka] This includes compounds including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0297] An embodiment of the present invention has the formula (Va): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , and R 20e at least three of are hydrogen.

[0298] An embodiment of the present invention has the formula (Vb): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0299] An embodiment of the present invention has the formula (Vc): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0300] An embodiment of the present invention has the formula (Vd): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0301] An embodiment of the present invention has the formula (Vd-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0302] An embodiment of the present invention has the formula (Vd-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0303] An embodiment of the present invention has the formula (Vd-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0304] An embodiment of the present invention has the formula (Vd-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0305] An embodiment of the present invention has the formula (Vd-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0306] An embodiment of the present invention has the formula (Ve): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20d are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloa Lukil, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0307] An embodiment of the present invention has the formula (Vf): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0308] An embodiment of the present invention has the formula (Vg): [ka] Hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts thereof, and and complexes, wherein Q 1 is 1 or 2, Q 2 is 1 or 2.

[0309] An embodiment of the present invention has the formula (Vh): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0310] An embodiment of the present invention has the formula (Vh-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0311] An embodiment of the present invention has the formula (Vh-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0312] An embodiment of the present invention has the formula (Vh-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0313] An embodiment of the present invention has the formula (Vh-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0314] An embodiment of the present invention has the formula (Vh-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0315] An embodiment of the present invention has the formula (Vi): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 cycloalkoxy , C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20e at least two of are hydrogen.

[0316] An embodiment of the present invention has the formula (Vj): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0317] An embodiment of the present invention has the formula (Vk): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0318] An embodiment of the present invention has the formula (VL): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0319] An embodiment of the present invention has the formula (VL-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0320] An embodiment of the present invention has the formula (VL-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0321] An embodiment of the present invention has the formula (VL-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0322] An embodiment of the present invention has the formula (VL-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0323] An embodiment of the present invention has the formula (VL-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0324] An embodiment of the present invention has the formula (Vm): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22, -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0325] An embodiment of the present invention has the formula (Vn): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0326] An embodiment of the present invention has the formula (Vo): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0327] An embodiment of the present invention has the formula (Vp): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0328] An embodiment of the present invention has the formula (Vp-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0329] An embodiment of the present invention has the formula (Vp-2): [ka] Hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts thereof, and and complexes, wherein Q 1 is 1 or 2, Q 2 is 1 or 2.

[0330] An embodiment of the present invention has the formula (Vp-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0331] An embodiment of the present invention has the formula (Vp-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0332] An embodiment of the present invention has the formula (Vp-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0333] An embodiment of the present invention has the formula (Vq): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0334] An embodiment of the present invention has the formula (Vr): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0335] An embodiment of the present invention has the formula (Vs): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0336] An embodiment of the present invention has the formula (Vt): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0337] An embodiment of the present invention has the formula (Vt-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0338] An embodiment of the present invention has the formula (Vt-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0339] An embodiment of the present invention has the formula (Vt-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0340] An embodiment of the present invention has the formula (Vt-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0341] An embodiment of the present invention has the formula (Vt-5): [ka] Hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts thereof, and and complexes, wherein Q 1 is 1 or 2, Q 2 is 1 or 2.

[0342] An embodiment of the present invention has the formula (Vu): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0343] An embodiment of the present invention has the formula (Vv): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0344] An embodiment of the present invention has the formula (Vw): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0345] An embodiment of the present invention has the formula (Vx): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0346] An embodiment of the present invention has the formula (Vx-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0347] An embodiment of the present invention has the formula (Vx-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0348] An embodiment of the present invention has the formula (Vx-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0349] An embodiment of the present invention has the formula (Vx-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0350] An embodiment of the present invention has the formula (Vx-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0351] An embodiment of the present invention has formula (VI): [ka] This includes compounds including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0352] In embodiments, the compound has a structure according to formula (XLVI): [ka] or a pharmaceutically acceptable salt thereof.

[0353] In embodiments, the compound has a structure according to formula (XLVIa): [ka] or a pharmaceutically acceptable salt thereof.

[0354] In embodiments, n is 1, 2, or 3. In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 1 or 2.

[0355] In embodiments, R 1 and R 2 Each of the 1-6 In embodiments, R 1 and R 2 Each of R is ethyl. 1 and R 2 Each of is methyl.

[0356] In embodiments, R 1 and R 2 together with the atoms to which they are attached, form one carbon-carbon double bond and / or O, S, SO, SO2, and NR 7 and forming a 5- to 8-membered ring optionally containing ring atoms selected from the group consisting of:

[0357] In embodiments, R 1 and R 2 together with the atoms to which they are attached form a C3-C8 cycloalkyl or a C5-C8 cycloalkenyl.

[0358] In embodiments, R 1 and R 2 are taken together with the atoms to which they are attached to form a C3-C8 cycloalkyl or C5-C8 cycloalkenyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, and cyclooctenyl. In embodiments, the C3-C8 cycloalkyl or C5-C8 cycloalkenyl is unsubstituted. In embodiments, the C3-C8 cycloalkyl or C5-C8 cycloalkenyl is substituted with 1, 2, 3, or 4 substituents (e.g., 1 or 2 substituents described herein). In embodiments, the substituent is oxo (=O), hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In embodiments, the substituents are selected from -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - iIt is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0359] In embodiments, R 1 and R 2 together with the atoms to which they are attached, form NR 7 In embodiments, the 5-8 membered ring is not further substituted. In embodiments, the 5-8 membered ring further comprises 1, 2, 3, or 4 substituents (e.g., 1 or 2 substituents described herein). In embodiments, the substituents are oxo (=O), hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In embodiments, the substituents are selected from -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0360] In embodiments, R 1 and R 2 are taken together and the nitrogen atom is NR 7 In embodiments, the pyrrolidinyl or piperidinyl group is not further substituted. In embodiments, the pyrrolidinyl or piperidinyl group further comprises one, two, three, or four substituents described herein.

[0361] In embodiments, R 7 is COR 8 and R 8 is a C1-6 straight chain alkyl.

[0362] In embodiments, R 7 is acetyl.

[0363] In embodiments, R 7 is SO2R 10c and R 10c is a C1-6 straight chain alkyl.

[0364] In embodiments, R 10c is methyl (i.e., R 7 is SO2Me).

[0365] In embodiments, R 5 is phenyl.

[0366] In embodiments, R 5 is substituted phenyl. In embodiments, R 5 is phenyl substituted with 1, 2, 3, 4, or 5 substituents (e.g., phenyl substituted with 1 or 2 substituents as described herein). In embodiments, the substituents are hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In an embodiment, the substituents are selected from the group consisting of -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - i It is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0367] In embodiments, R 5is selected from the group consisting of hydroxylphenyl, fluorophenyl, chlorophenyl, bromophenyl, cyanophenyl, tolyl, methoxylphenyl, difluorophenyl, dichlorophenyl, chloro-fluorophenyl, dimethylphenyl, trifluoromethylphenyl, di(trifluoromethyl)phenyl.

[0368] In embodiments, R 5 is selected from the group consisting of 4-hydroxyphenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 4-fluoro-3-chlorophenyl, 4-cyanophenyl, 2-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-isopropylphenyl, 4-trifluoromethylphenyl, 2-morpholinophenyl, and 4-methyl-2-morpholinophenyl.

[0369] In embodiments, R 5 is pyridyl. In embodiments, R 5 is 2-pyridyl. In embodiments, R 5 is 3-pyridyl. In embodiments, R 5 is 4-pyridyl. In embodiments, the pyridyl is unsubstituted. In embodiments, the pyridyl is substituted with 1, 2, 3, or 4 substituents (e.g., pyridyl substituted with 1 or 2 substituents as described herein). In embodiments, the substituents are hydroxyl, halo, cyano, C 1-6 Alkoxy, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 1-6 Haloalkyl, C 3-8 In an embodiment, the substituents are selected from the group consisting of -OH, -F, -Cl, -Br, -I, -CN, -OMe, -OEt, -O n Pr, -O i Pr, -OCF3, -Me, -Et, - n Pr, - iIt is selected from the group consisting of Pr, -CF3, cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, and morpholino.

[0370] An embodiment of the present invention has formula (VIa): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , and R 20e at least three of are hydrogen.

[0371] An embodiment of the present invention has formula (VIb): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1is 1 or 2, Q 2 is 1 or 2.

[0372] An embodiment of the present invention has formula (VIc): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0373] An embodiment of the present invention has formula (VId): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0374] An embodiment of the present invention has the formula (Vid-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0375] An embodiment of the present invention has the formula (Vid-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0376] An embodiment of the present invention has the formula (Vid-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0377] An embodiment of the present invention has the formula (Vid-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0378] An embodiment of the present invention has the formula (Vid-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0379] An embodiment of the present invention has formula (VIe): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20d are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0380] An embodiment of the present invention has the formula (VIf): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0381] An embodiment of the present invention has the formula (VIg): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0382] An embodiment of the present invention has formula (VIh): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0383] An embodiment of the present invention has formula (VIh-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0384] An embodiment of the present invention has formula (VIh-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1is 1 or 2, Q 2 is 1 or 2.

[0385] An embodiment of the present invention has formula (VIh-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0386] An embodiment of the present invention has the formula (VIh-): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0387] An embodiment of the present invention has formula (VIh-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0388] An embodiment of the present invention has formula (VIi): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20e at least two of are hydrogen.

[0389] An embodiment of the present invention has formula (VIj): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0390] An embodiment of the present invention has the formula (VIk): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0391] An embodiment of the present invention has the formula (VIL): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0392] An embodiment of the present invention has the formula (VIL-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0393] An embodiment of the present invention has the formula (VIL-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0394] An embodiment of the present invention has the formula (VIL-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0395] An embodiment of the present invention has the formula (VIL-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0396] An embodiment of the present invention has the formula (VIL-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0397] An embodiment of the present invention has the formula (VIm): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R20b , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0398] An embodiment of the present invention has the formula (VIn): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0399] An embodiment of the present invention has formula (VIo): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2is 1 or 2.

[0400] An embodiment of the present invention has the formula (VIp): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0401] An embodiment of the present invention has the formula (VIp-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0402] An embodiment of the present invention has the formula (VIp-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0403] An embodiment of the present invention has the formula (VIp-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0404] An embodiment of the present invention has the formula (VIp-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0405] An embodiment of the present invention has the formula (VIp-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0406] An embodiment of the present invention has formula (VIq): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20gare independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, Call C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0407] An embodiment of the present invention has the formula (VIr): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0408] An embodiment of the present invention has formula (VIs): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q2 is 1 or 2.

[0409] An embodiment of the present invention has the formula (VIt): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0410] An embodiment of the present invention has the formula (VIt-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0411] An embodiment of the present invention has formula (VIt-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0412] An embodiment of the present invention has the formula (VIt-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0413] An embodiment of the present invention has the formula (VIt-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0414] An embodiment of the present invention has the formula (VIt-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0415] An embodiment of the present invention has formula (VIu): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20gare independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0416] An embodiment of the present invention has formula (VIv): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0417] An embodiment of the present invention has the formula (VIw): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2is 1 or 2.

[0418] An embodiment of the present invention has the formula (VIx): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0419] An embodiment of the present invention has formula (VIx-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0420] An embodiment of the present invention has formula (VIx-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0421] An embodiment of the present invention has formula (VIx-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0422] An embodiment of the present invention has formula (VIx-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0423] An embodiment of the present invention has formula (VIx-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0424] An embodiment of the present invention has formula (VII): [ka] This includes compounds including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0425] An embodiment of the present invention has formula (VIIa): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , and R 20e at least three of are hydrogen.

[0426] An embodiment of the present invention has formula (VIIb): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0427] An embodiment of the present invention has formula (VIIc): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0428] An embodiment of the present invention has formula (VIId): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0429] An embodiment of the present invention has formula (VIId-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0430] An embodiment of the present invention has formula (VIId-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0431] An embodiment of the present invention has formula (VIId-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0432] An embodiment of the present invention has formula (VIId-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0433] An embodiment of the present invention has formula (VIId-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0434] An embodiment of the present invention has formula (VIIe): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a, R 20b , R 20c , and R 20d are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0435] An embodiment of the present invention has formula (VIIf): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0436] An embodiment of the present invention has formula (VIIg): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2is 1 or 2.

[0437] An embodiment of the present invention has formula (VIIh): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0438] An embodiment of the present invention has formula (VIIh-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0439] An embodiment of the present invention has formula (VIIh-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0440] An embodiment of the present invention has formula (VIIh-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0441] An embodiment of the present invention has formula (VIIh-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0442] An embodiment of the present invention has formula (VIIh-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0443] An embodiment of the present invention has formula (VIIi): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20e at least two of are hydrogen.

[0444] An embodiment of the present invention has formula (VIIj): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0445] An embodiment of the present invention has formula (VIIk): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0446] An embodiment of the present invention has the formula (VIIL): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0447] An embodiment of the present invention has the formula (VIIL-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0448] An embodiment of the present invention has the formula (VIIL-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0449] An embodiment of the present invention has the formula (VIIL-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0450] An embodiment of the present invention has the formula (VIIL-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0451] An embodiment of the present invention has the formula (VIIL-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0452] An embodiment of the present invention has the formula (VIIm): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20d , and R 20e are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , and R 20d at least two of are hydrogen.

[0453] An embodiment of the present invention has the formula (VIIn): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0454] An embodiment of the present invention has formula (VIIo): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0455] An embodiment of the present invention has formula (VIIp): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X1 O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0456] An embodiment of the present invention has the formula (VIIp-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0457] An embodiment of the present invention has formula (VIIp-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0458] An embodiment of the present invention has formula (VIIp-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0459] An embodiment of the present invention has formula (VIIp-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0460] An embodiment of the present invention has the formula (VIIp-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0461] An embodiment of the present invention has formula (VIIq): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C3-7 Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0462] An embodiment of the present invention has formula (VIIr): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0463] An embodiment of the present invention has formula (VIIs): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0464] An embodiment of the present invention has formula (VIIt): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1O, S, SO, SO2, and NR 7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0465] An embodiment of the present invention has formula (VIIt-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0466] An embodiment of the present invention has formula (VIIt-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0467] An embodiment of the present invention has formula (VIIt-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0468] An embodiment of the present invention has formula (VIIt-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0469] An embodiment of the present invention has the formula (VIIt-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0470] An embodiment of the present invention has formula (VIIu): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g are independently hydrogen, -CN, -NO2, -OH, halogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, C 3-7 Cycloalkyl, C 1-6 Linear alkoxy, C 3-7 Branched alkoxy, C 3-7 Cycloalkoxy, C 1-6 Straight chain haloalkyl, C 3-7 Branched haloalkyl, C 1-6 Straight chain haloalkoxy, C 3-7Branched haloalkoxy, SH, SC 1-6 Straight chain alkyl, SC 3-7 Branched alkyl, SC 3-7 Cycloalkyl, SO2C 1-6 Linear alkyl, SO2C 3-7 Branched alkyl, SO2C 3-7 Cycloalkyl, SO2NH2, SO2NHR 21 , NHSO2R 22 , -NR 23a R 23b , NHC(O)R 24 , C(O)NHR 24 , C(O)N(R 24 )2, morpholino, and [ka] is selected from the group consisting of R 21 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 22 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23a independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 23b independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 24 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R25 independently in each occurrence: hydrogen, C 1-6 Straight chain alkyl, C 3-7 Branched alkyl, and C 3-7 cycloalkyl; R 20a , R 20b , R 20c , R 20d , R 20e , R 20f , and R 20g at least five of which are hydrogen.

[0471] An embodiment of the present invention has formula (VIIv): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0472] An embodiment of the present invention has formula (VIIw): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0473] An embodiment of the present invention has formula (VIIx): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: X 1 O, S, SO, SO2, and NR7 is selected from the group consisting of Q 1 is 1 or 2, Q 2 is 1 or 2.

[0474] An embodiment of the present invention has formula (VIIx-1): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0475] An embodiment of the present invention has formula (VIIx-2): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0476] An embodiment of the present invention has formula (VIIx-3): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0477] An embodiment of the present invention has formula (VIIx-4): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0478] An embodiment of the present invention has formula (VIIx-5): [ka] including hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof, wherein: Q 1 is 1 or 2, Q 2 is 1 or 2.

[0479] In some embodiments, A is [ka] is.

[0480] In some embodiments, A is [ka] is.

[0481] In some embodiments, A is [ka] is.

[0482] In some embodiments, R 1 is hydrogen.

[0483] In some embodiments, R 1 is C 1-6 It is a straight chain alkyl.

[0484] In some embodiments, R 1 is C 3-7 It is a branched alkyl.

[0485] In some embodiments, R 2 is hydrogen.

[0486] In some embodiments, R 2 is C 1-6 It is a straight chain alkyl.

[0487] In some embodiments, R 2 is C 3-7 It is a branched alkyl.

[0488] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 5 ring atoms.

[0489] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring having 5 ring atoms and containing a double bond.

[0490] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 6 ring atoms.

[0491] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring having 6 ring atoms and containing a double bond.

[0492] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 7 ring atoms.

[0493] In some embodiments, R1 and R 2 together with the atoms to which they are attached form a ring having seven ring atoms and containing a double bond.

[0494] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 6 ring atoms (one of which is O).

[0495] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 7 ring atoms (one of which is O).

[0496] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 8 ring atoms (one of which is O).

[0497] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 6 ring atoms (one of which is S).

[0498] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 7 ring atoms (one of which is S).

[0499] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 8 ring atoms (one of which is S).

[0500] In some embodiments, R 1 and R 2together with the atoms to which they are attached form a ring with 6 ring atoms (one of which is SO).

[0501] In some embodiments, R 1 and R 2 together with the atoms to which they are bonded, It forms a ring with 7 ring atoms, one of which is SO.

[0502] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with 8 ring atoms (one of which is SO).

[0503] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with six ring atoms (one of which is SO2).

[0504] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with seven ring atoms (one of which is SO2).

[0505] In some embodiments, R 1 and R 2 together with the atoms to which they are attached form a ring with eight ring atoms (one of which is SO2).

[0506] In some embodiments, R 1 and R 2 together with the atoms to which they are attached, form six ring atoms (one of which is NR 7 The ring is formed with

[0507] In some embodiments, R 1 and R 2together with the atoms to which they are attached, form seven ring atoms (one of which is NR 7 The ring is formed with

[0508] In some embodiments, R 1 and R 2 together with the atoms to which they are attached, form eight ring atoms (one of which is NR 7 The ring is formed with

[0509] In some embodiments, R 3 is optionally substituted phenyl.

[0510] In some embodiments, R 3 is an optionally substituted naphthylene-1-yl.

[0511] In some embodiments, R 3 is an optionally substituted naphthylene-2-yl.

[0512] In some embodiments, R 3 is an optionally substituted 2-pyridyl.

[0513] In some embodiments, R 3 is an optionally substituted 3-pyridyl.

[0514] In some embodiments, R 3 is an optionally substituted 4-pyridyl.

[0515] In some embodiments, R 3 teeth, [ka] is.

[0516] In some embodiments, R 4 is optionally substituted phenyl.

[0517] In some embodiments, R 4 is an optionally substituted naphthylene-1-yl.

[0518] In some embodiments, R 4 is an optionally substituted naphthylene-2-yl.

[0519] In some embodiments, R 4 is an optionally substituted 2-pyridyl.

[0520] In some embodiments, R 4 is an optionally substituted 3-pyridyl.

[0521] In some embodiments, R 4 is an optionally substituted 4-pyridyl.

[0522] In some embodiments, R 4 teeth, [ka] is.

[0523] In some embodiments, R 5 is optionally substituted phenyl.

[0524] In some embodiments, R 5 is an optionally substituted naphthylene-1-yl.

[0525] In some embodiments, R 5 is an optionally substituted naphthylene-2-yl.

[0526] In some embodiments, R 5 is an optionally substituted 2-pyridyl.

[0527] In some embodiments, R 5 is an optionally substituted 3-pyridyl.

[0528] In some embodiments, R 5 is an optionally substituted 4-pyridyl.

[0529] In some embodiments, R 5 teeth, [ka] is.

[0530] In some embodiments, R6 is optionally substituted phenyl.

[0531] In some embodiments, R 6 is an optionally substituted naphthylene-1-yl.

[0532] In some embodiments, R 6 is an optionally substituted naphthylene-2-yl.

[0533] In some embodiments, R 6 is an optionally substituted 2-pyridyl.

[0534] In some embodiments, R 6 is an optionally substituted 3-pyridyl.

[0535] In some embodiments, R 6 is an optionally substituted 4-pyridyl.

[0536] In some embodiments, R 7 is H.

[0537] In some embodiments, R 7 is C 1-6 It is a straight chain alkyl.

[0538] In some embodiments, R 7 is C 3-7 It is a branched alkyl.

[0539] In some embodiments, R7 is C 3-7 It is cycloalkyl.

[0540] In some embodiments, R 7 is optionally substituted phenyl.

[0541] In some embodiments, R 7 is optionally substituted benzyl.

[0542] In some embodiments, R 7 is COR 8 is.

[0543] In some embodiments, R 7 is CO2R 9 is.

[0544] In some embodiments, R 7 CONR 10a R 10b is.

[0545] In some embodiments, R 7 is SO2NR 10a R 10b is.

[0546] In some embodiments, R 7 is SO2R 10c is.

[0547] In some embodiments, R 8 is the selected H.

[0548] In some embodiments, R 8 is C 1-6 It is a straight chain alkyl.

[0549] In some embodiments, R 8 is C 3-7 It is a branched alkyl.

[0550] In some embodiments, R 8 is C3-7 It is cycloalkyl.

[0551] In some embodiments, R 9 is C 1-6 It is a straight chain alkyl.

[0552] In some embodiments, R 9 is C 3-7 It is a branched alkyl.

[0553] In some embodiments, R 9 is C 3-7 It is cycloalkyl.

[0554] In some embodiments, R 10a is H.

[0555] In some embodiments, R 10a is C 1-6 It is a straight chain alkyl.

[0556] In some embodiments, R 10a is C 3-7 It is a branched alkyl.

[0557] In some embodiments, R 10a is C 3-7 It is cycloalkyl.

[0558] In some embodiments, R 10b is H.

[0559] In some embodiments, R 10b is C 1-6 It is a straight chain alkyl.

[0560] In some embodiments, R 10b is C 3-7 It is a branched alkyl.

[0561] In some embodiments, R 10b is C 3-7 It is cycloalkyl.

[0562] In some embodiments, R 10c is C 1-6 It is a straight chain alkyl.

[0563] In some embodiments, R 10c is C 3-7 It is a branched alkyl.

[0564] In some embodiments, R 10c is C 3-7 It is cycloalkyl.

[0565] In some embodiments, R 10c is C 1-6 It is a straight chain haloalkyl.

[0566] In some embodiments, R 10c is C 3-7 It is a branched haloalkyl.

[0567] In some embodiments, R 10c is -(CH2) q It is CN.

[0568] In some embodiments, R 10c is -(CH2) q SO2R 11 is.

[0569] In some embodiments, R 10c is -(CH2) q OR 12 is.

[0570] In some embodiments, R 10c teeth, [ka] is.

[0571] In some embodiments, R 10c teeth, [ka] is.

[0572] In some embodiments, R 10c teeth, [ka] is.

[0573] In some embodiments, R 10c teeth, [ka] is.

[0574] In some embodiments, R 10c teeth, [ka] is.

[0575] In some embodiments, R 10c teeth, [ka] is.

[0576] In some embodiments, R 10c teeth, [ka] is.

[0577] In some embodiments, R 10c teeth, [ka] is.

[0578] In some embodiments, R 10c teeth, [ka] is.

[0579] In some embodiments, R 10c teeth, [ka] is.

[0580] In some embodiments, R 10c teeth, [ka] is.

[0581] In some embodiments, R 10c teeth, [ka] is.

[0582] In some embodiments, R 11 is C 1-6 It is a straight chain alkyl.

[0583] In some embodiments, R 11 is C 3-7 It is a branched alkyl.

[0584] In some embodiments, R 11 is C 3-7 It is cycloalkyl.

[0585] In some embodiments, R 12 is C 1-6 It is a straight chain alkyl.

[0586] In some embodiments, R 12 is C 3-7 It is a branched alkyl.

[0587] In some embodiments, R 12 is C 3-7 It is cycloalkyl.

[0588] In some embodiments, R 1a is H.

[0589] In some embodiments, R 1a is OH.

[0590] In some embodiments, R 1a is NO2.

[0591] In some embodiments, R 1a is a halogen.

[0592] In some embodiments, R 1a is CN.

[0593] In some embodiments, R 1a is C 1-6 It is a straight chain alkyl.

[0594] In some embodiments, R 1a is C 3-7 It is a branched alkyl.

[0595] In some embodiments, R 1a is C 3-7 It is cycloalkyl.

[0596] In some embodiments, R 1a is C 1-6 It is a straight chain alkoxy.

[0597] In some embodiments, R 1a is C 3-7 It is a branched alkoxy.

[0598] In some embodiments, R 1a is C 3-7 It is cycloalkoxy.

[0599] In some embodiments, R 1a is C 1-6 It is a straight chain haloalkyl.

[0600] In some embodiments, R 1a is C 3-7 It is a branched haloalkyl.

[0601] In some embodiments, R 1a is C 1-6 It is a straight chain haloalkoxy.

[0602] In some embodiments, R 1a is -S(C 1-6 (straight-chain alkyl).

[0603] In some embodiments, R 1a is S(C 3-7 branched alkyl).

[0604] In some embodiments, R 1a is -S(C 3-7 cycloalkyl).

[0605] In some embodiments, R 1a is COR 13 is.

[0606] In some embodiments, R 1a is CO2R 14 is.

[0607] In some embodiments, R 1a CONR 15a R 15b is.

[0608] In some embodiments, R 1a is SO2NR 15a R 15b is.

[0609] In some embodiments, R 1a is NR 16a R 16b is.

[0610] In some embodiments, R 1a is NR16a COR 17 is.

[0611] In some embodiments, R 1a is NR 16a SO2R 18 is.

[0612] In some embodiments, R 1a is NR 16a SO2NR 19a R 19b is.

[0613] In some embodiments, R 1b is H.

[0614] In some embodiments, R 1b is OH.

[0615] In some embodiments, R 1b is NO2.

[0616] In some embodiments, R 1b is a halogen.

[0617] In some embodiments, R 1b is CN.

[0618] In some embodiments, R 1b is C 1-6 It is a straight chain alkyl.

[0619] In some embodiments, R 1b is C 3-7 It is a branched alkyl.

[0620] In some embodiments, R 1b is C 3-7 It is cycloalkyl.

[0621] In some embodiments, R 1b is C 1-6 It is a straight chain alkoxy.

[0622] In some embodiments, R 1b is C 3-7 It is a branched alkoxy.

[0623] In some embodiments, R 1b is C 3-7 It is cycloalkoxy.

[0624] In some embodiments, R 1b is C 1-6 It is a straight chain haloalkyl.

[0625] In some embodiments, R 1b is C 3-7 It is a branched haloalkyl.

[0626] In some embodiments, R 1b is C 1-6 It is a straight chain haloalkoxy.

[0627] In some embodiments, R 1b is -S(C 1-6 (straight-chain alkyl).

[0628] In some embodiments, R 1b is S(C 3-7 branched alkyl).

[0629] In some embodiments, R 1b is -S(C 3-7 cycloalkyl).

[0630] In some embodiments, R 1b is COR 13 is.

[0631] In some embodiments, R 1b is CO2R 14 is.

[0632] In some embodiments, R 1b CONR 15a R15b is.

[0633] In some embodiments, R 1b is SO2NR 15a R 15b is.

[0634] In some embodiments, R 1b is NR 16a R 16b is.

[0635] In some embodiments, R 1b is NR 16a COR 17 is.

[0636] In some embodiments, R 1b is NR 16a SO2R 18 is.

[0637] In some embodiments, R 1b is NR 16a SO2NR 19a R 19b is.

[0638] In some embodiments, R 1c is H.

[0639] In some embodiments, R 1c is OH.

[0640] In some embodiments, R 1c is NO2.

[0641] In some embodiments, R 1c is a halogen.

[0642] In some embodiments, R 1c is CN.

[0643] In some embodiments, R 1c is C 1-6 It is a straight chain alkyl.

[0644] In some embodiments, R 1c is C 3-7 It is a branched alkyl.

[0645] In some embodiments, R 1c is C 3-7 It is cycloalkyl.

[0646] In some embodiments, R 1c is C 1-6 It is a straight chain alkoxy.

[0647] In some embodiments, R 1c is C 3-7 It is a branched alkoxy.

[0648] In some embodiments, R 1c is C 3-7 It is cycloalkoxy.

[0649] In some embodiments, R 1c is C 1-6 It is a straight chain haloalkyl.

[0650] In some embodiments, R 1c is C 3-7 It is a branched haloalkyl.

[0651] In some embodiments, R 1c is C 1-6 It is a straight chain haloalkoxy.

[0652] In some embodiments, R 1c is -S(C 1-6 (straight-chain alkyl).

[0653] In some embodiments, R 1c is S(C 3-7 branched alkyl).

[0654] In some embodiments, R 1c is -S(C3-7 cycloalkyl).

[0655] In some embodiments, R 1c is COR 13 is.

[0656] In some embodiments, R 1c is CO2R 14 is.

[0657] In some embodiments, R 1c CONR 15a R 15b is.

[0658] In some embodiments, R 1c is SO2NR 15a R 15b is.

[0659] In some embodiments, R 1c is NR 16a R 16b is.

[0660] In some embodiments, R 1c is NR 16a COR 17 is.

[0661] In some embodiments, R 1c is NR 16a SO2R 18 is.

[0662] In some embodiments, R 1c is NR 16a SO2NR 19a R 19b is.

[0663] In some embodiments, R 1d is H.

[0664] In some embodiments, R 1d is OH.

[0665] In some embodiments, R 1d is NO2.

[0666] In some embodiments, R 1d is a halogen.

[0667] In some embodiments, R 1d is CN.

[0668] In some embodiments, R 1d is C 1-6 It is a straight chain alkyl.

[0669] In some embodiments, R 1d is C 3-7 It is a branched alkyl.

[0670] In some embodiments, R 1d is C 3-7 It is cycloalkyl.

[0671] In some embodiments, R 1d is C 1-6 It is a straight chain alkoxy.

[0672] In some embodiments, R 1d is C 3-7 It is a branched alkoxy.

[0673] In some embodiments, R 1d is C 3-7 It is cycloalkoxy.

[0674] In some embodiments, R 1d is C 1-6 It is a straight chain haloalkyl.

[0675] In some embodiments, R 1d is C 3-7 It is a branched haloalkyl.

[0676] In some embodiments, R 1d is C1-6 It is a straight chain haloalkoxy.

[0677] In some embodiments, R 1d is -S(C 1-6 (straight-chain alkyl).

[0678] In some embodiments, R 1d is S(C 3-7 branched alkyl).

[0679] In some embodiments, R 1d is —S(C3-7 cycloalkyl).

[0680] In some embodiments, R 1d is COR 13 is.

[0681] In some embodiments, R 1d is CO2R 14 is.

[0682] In some embodiments, R 1d CONR 15a R 15b is.

[0683] In some embodiments, R 1d is SO2NR 15a R 15b is.

[0684] In some embodiments, R 1d is NR 16a R 16b is.

[0685] In some embodiments, R 1d is NR 16a COR 17 is.

[0686] In some embodiments, R 1d is NR 16a SO2R 18 is.

[0687] In some embodiments, R 1d is NR 16a SO2NR 19a R 19b is.

[0688] In some embodiments, R 1e is H.

[0689] In some embodiments, R 1e is OH.

[0690] In some embodiments, R 1e is NO2.

[0691] In some embodiments, R 1e is a halogen.

[0692] In some embodiments, R 1e is CN.

[0693] In some embodiments, R 1e is C 1-6 It is a straight chain alkyl.

[0694] In some embodiments, R 1e is C 3-7 It is a branched alkyl.

[0695] In some embodiments, R 1e is C 3-7 It is cycloalkyl.

[0696] In some embodiments, R 1e is C 1-6 It is a straight chain alkoxy.

[0697] In some embodiments, R 1e is C 3-7 It is a branched alkoxy.

[0698] In some embodiments, R 1e is C3-7 It is cycloalkoxy.

[0699] In some embodiments, R 1e is C 1-6 It is a straight chain haloalkyl.

[0700] In some embodiments, R 1e is C 3-7 It is a branched haloalkyl.

[0701] In some embodiments, R 1e is C 1-6 It is a straight chain haloalkoxy.

[0702] In some embodiments, R 1e is -S(C 1-6 (straight-chain alkyl).

[0703] In some embodiments, R 1e is S(C 3-7 branched alkyl).

[0704] In some embodiments, R 1e is —S(C3-7 cycloalkyl).

[0705] In some embodiments, R 1e is COR 13 is.

[0706] In some embodiments, R 1e is CO2R 14 is.

[0707] In some embodiments, R 1e CONR 15a R 15b is.

[0708] In some embodiments, R 1e is SO2NR 15a R 15b is.

[0709] In some embodiments, R 1e is NR 16a R 16b is.

[0710] In some embodiments, R 1e is NR 16a COR 17 is.

[0711] In some embodiments, R 1e is NR 16a SO2R 18 is.

[0712] In some embodiments, R 1e is NR 16a SO2NR 19a R 19b is.

[0713] In some embodiments, R 13 is H.

[0714] In some embodiments, R 13 is C 1-6 It is a straight chain alkyl.

[0715] In some embodiments, R 13 is C 3-7 It is a branched alkyl.

[0716] In some embodiments, R 13 is C 3-7 It is cycloalkyl.

[0717] In some embodiments, R 14 is C 1-6 It is a straight chain alkyl.

[0718] In some embodiments, R 14 is C 3-7 It is a branched alkyl.

[0719] In some embodiments, R 14 is C 3-7It is cycloalkyl.

[0720] In some embodiments, R 15a is H.

[0721] In some embodiments, R 15a is C 1-6 It is a straight chain alkyl.

[0722] In some embodiments, R 15a is C 3-7 It is a branched alkyl.

[0723] In some embodiments, R 15a is C 3-7 It is cycloalkyl.

[0724] In some embodiments, R 15b is H.

[0725] In some embodiments, R 15b is C 1-6 It is a straight chain alkyl.

[0726] In some embodiments, R 15b is C 3-7 It is a branched alkyl.

[0727] In some embodiments, R 15b is C 3-7 It is cycloalkyl.

[0728] In some embodiments, R 16a is H.

[0729] In some embodiments, R 16a is C 1-6 It is a straight chain alkyl.

[0730] In some embodiments, R 16a is C 3-7 It is a branched alkyl.

[0731] In some embodiments, R 16a is C 3-7 It is cycloalkyl.

[0732] In some embodiments, R 16b is H.

[0733] In some embodiments, R 16b is C 1-6 It is a straight chain alkyl.

[0734] In some embodiments, R 16b is C 3-7 It is a branched alkyl.

[0735] In some embodiments, R 16b is C 3-7 It is cycloalkyl.

[0736] In some embodiments, R 17 is H.

[0737] In some embodiments, R 17 is C 1-6 It is a straight chain alkyl.

[0738] In some embodiments, R 17 is C 3-7 It is a branched alkyl.

[0739] In some embodiments, R 17 is C 3-7 It is cycloalkyl.

[0740] In some embodiments, R 18 is C 1-6 It is a straight chain alkyl.

[0741] In some embodiments, R 18 is C 3-7 It is a branched alkyl.

[0742] In some embodiments, R 18 is C3-7 It is cycloalkyl.

[0743] In some embodiments, R 19a is C 1-6 It is a straight chain alkyl.

[0744] In some embodiments, R 19a is C 3-7 It is a branched alkyl.

[0745] In some embodiments, R 19a is C 3-7 It is cycloalkyl.

[0746] In some embodiments, R 19b is C 1-6 It is a straight chain alkyl.

[0747] In some embodiments, R 19b is C 3-7 It is a branched alkyl.

[0748] In some embodiments, R 19b is C 3-7 It is cycloalkyl.

[0749] In some embodiments, n is 1.

[0750] In some embodiments, n is 2.

[0751] In some embodiments, n is 3.

[0752] In some embodiments, n is 4.

[0753] In some embodiments, m is 1.

[0754] In some embodiments, m is 2.

[0755] In some embodiments, m is 3.

[0756] In some embodiments, R 20a is hydrogen.

[0757] In some embodiments, R 20a is -CN.

[0758] In some embodiments, R 20a is -NO2.

[0759] In some embodiments, R 20a is -OH.

[0760] In some embodiments, R 20a is a halogen.

[0761] In some embodiments, R 20a is C 1-6 It is a straight chain alkyl.

[0762] In some embodiments, R 20a is C 3-7 It is a branched alkyl.

[0763] In some embodiments, R 20a is C 3-7 It is cycloalkyl.

[0764] In some embodiments, R 20a is C 1-6 It is a straight chain alkoxy.

[0765] In some embodiments, R 20a is C 3-7 It is a branched alkoxy.

[0766] In some embodiments, R 20a is C 3-7 It is cycloalkoxy.

[0767] In some embodiments, R 20a is C 1-6 It is a straight chain haloalkyl.

[0768] In some embodiments, R 20a is C 3-7 It is a branched haloalkyl.

[0769] In some embodiments, R 20a is C 1-6 It is a straight chain haloalkoxy.

[0770] In some embodiments, R 20a is C 3-7 It is a branched haloalkoxy.

[0771] In some embodiments, R 20a is SH.

[0772] In some embodiments, R 20a is SC 1-6 It is a straight chain alkyl.

[0773] In some embodiments, R 20a is SC 3-7 It is a branched alkyl.

[0774] In some embodiments, R 20a is SC 3-7 It is cycloalkyl.

[0775] In some embodiments, R 20a is SO2C 1-6 It is a straight chain alkyl.

[0776] In some embodiments, R 20a is SO2C 3-7 It is a branched alkyl.

[0777] In some embodiments, R 20a is SO2C 3-7 It is cycloalkyl.

[0778] In some embodiments, R 20a is SO2NH2.

[0779] In some embodiments, R 20a is SO2NHR 21 is.

[0780] In some embodiments, R 20a is NHSO2R 22 is.

[0781] In some embodiments, R 20a is -NR 23a R 23b is.

[0782] In some embodiments, R 20a is NHC(O)R 24 is.

[0783] In some embodiments, R 20a is C(O)NHR 24 is.

[0784] In some embodiments, R 20a is C(O)N(R 24 )2.

[0785] In some embodiments, R 20a is a morpholino.

[0786] In some embodiments, R 20a teeth, [ka] is.

[0787] In some embodiments, R 20b is hydrogen.

[0788] In some embodiments, R 20b is -CN.

[0789] In some embodiments, R 20b is -NO2.

[0790] In some embodiments, R 20b is -OH.

[0791] In some embodiments, R 20b is a halogen.

[0792] In some embodiments, R 20b is C 1-6 It is a straight chain alkyl.

[0793] In some embodiments, R 20b is C 3-7 It is a branched alkyl.

[0794] In some embodiments, R 20b is C 3-7 It is cycloalkyl.

[0795] In some embodiments, R 20b is C 1-6 It is a straight chain alkoxy.

[0796] In some embodiments, R 20b is C 3-7 It is a branched alkoxy.

[0797] In some embodiments, R 20b is C 3-7 It is cycloalkoxy.

[0798] In some embodiments, R 20b is C 1-6 It is a straight chain haloalkyl.

[0799] In some embodiments, R 20b is C 3-7 It is a branched haloalkyl.

[0800] In some embodiments, R 20b is C 1-6 It is a straight chain haloalkoxy.

[0801] In some embodiments, R 20b is C 3-7 It is a branched haloalkoxy.

[0802] In some embodiments, R 20b is SH.

[0803] In some embodiments, R 20b is SC 1-6 It is a straight chain alkyl.

[0804] In some embodiments, R 20b is SC 3-7 It is a branched alkyl.

[0805] In some embodiments, R 20b is SC 3-7 It is cycloalkyl.

[0806] In some embodiments, R 20b is SO2C 1-6 It is a straight chain alkyl.

[0807] In some embodiments, R 20b is SO2C 3-7 It is a branched alkyl.

[0808] In some embodiments, R 20b is SO2C 3-7 It is cycloalkyl.

[0809] In some embodiments, R 20b is SO2NH2.

[0810] In some embodiments, R 20b is SO2NHR 21 is.

[0811] In some embodiments, R 20b is NHSO2R 22 is.

[0812] In some embodiments, R 20b is -NR 23a R 23b is.

[0813] In some embodiments, R 20b is NHC(O)R 24 is.

[0814] In some embodiments, R 20b is C(O)NHR 24 is.

[0815] In some embodiments, R 20b is C(O)N(R 24 )2.

[0816] In some embodiments, R 20b is a morpholino.

[0817] In some embodiments, R 20b teeth, [ka] is.

[0818] In some embodiments, R 20c is hydrogen.

[0819] In some embodiments, R 20c is -CN.

[0820] In some embodiments, R 20c is -NO2.

[0821] In some embodiments, R 20c is -OH.

[0822] In some embodiments, R 20c is a halogen.

[0823] In some embodiments, R 20c is C1-6 It is a straight chain alkyl.

[0824] In some embodiments, R 20c is C 3-7 It is a branched alkyl.

[0825] In some embodiments, R 20c is C 3-7 It is cycloalkyl.

[0826] In some embodiments, R 20c is C 1-6 It is a straight chain alkoxy.

[0827] In some embodiments, R 20c is C 3-7 It is a branched alkoxy.

[0828] In some embodiments, R 20c is C 3-7 It is cycloalkoxy.

[0829] In some embodiments, R 20c is C 1-6 It is a straight chain haloalkyl.

[0830] In some embodiments, R 20c is C 3-7 It is a branched haloalkyl.

[0831] In some embodiments, R 20c is C 1-6 It is a straight chain haloalkoxy.

[0832] In some embodiments, R 20c is C 3-7 It is a branched haloalkoxy.

[0833] In some embodiments, R 20c is SH.

[0834] In some embodiments, R 20c is SC1-6 It is a straight chain alkyl.

[0835] In some embodiments, R 20c is SC 3-7 It is a branched alkyl.

[0836] In some embodiments, R 20c is SC 3-7 It is cycloalkyl.

[0837] In some embodiments, R 20c is SO2C 1-6 It is a straight chain alkyl.

[0838] In some embodiments, R 20c is SO2C 3-7 It is a branched alkyl.

[0839] In some embodiments, R 20c is SO2C 3-7 It is cycloalkyl.

[0840] In some embodiments, R 20c is SO2NH2.

[0841] In some embodiments, R 20c is SO2NHR 21 is.

[0842] In some embodiments, R 20c is NHSO2R 22 is.

[0843] In some embodiments, R 20c is -NR 23a R 23b is.

[0844] In some embodiments, R 20c is NHC(O)R 24 is.

[0845] In some embodiments, R 20cis C(O)NHR 24 is.

[0846] In some embodiments, R 20c is C(O)N(R 24 )2.

[0847] In some embodiments, R 20c is a morpholino.

[0848] In some embodiments, R 20c teeth, [ka] is.

[0849] In some embodiments, R 20d is hydrogen.

[0850] In some embodiments, R 20d is -CN.

[0851] In some embodiments, R 20d is -NO2.

[0852] In some embodiments, R 20d is -OH.

[0853] In some embodiments, R 20d is a halogen.

[0854] In some embodiments, R 20d is C 1-6 It is a straight chain alkyl.

[0855] In some embodiments, R 20d is C 3-7 It is a branched alkyl.

[0856] In some embodiments, R 20d is C 3-7 It is cycloalkyl.

[0857] In some embodiments, R 20d is C 1-6 It is a straight chain alkoxy.

[0858] In some embodiments, R 20d is C 3-7 It is a branched alkoxy.

[0859] In some embodiments, R 20d is C 3-7 It is cycloalkoxy.

[0860] In some embodiments, R 20d is C 1-6 It is a straight chain haloalkyl.

[0861] In some embodiments, R 20d is C 3-7 It is a branched haloalkyl.

[0862] In some embodiments, R 20d is C 1-6 It is a straight chain haloalkoxy.

[0863] In some embodiments, R 20d is C 3-7 It is a branched haloalkoxy.

[0864] In some embodiments, R 20d is SH.

[0865] In some embodiments, R 20d is SC 1-6 It is a straight chain alkyl.

[0866] In some embodiments, R 20d is SC 3-7 It is a branched alkyl.

[0867] In some embodiments, R 20d is SC 3-7 It is cycloalkyl.

[0868] In some embodiments, R 20d is SO2C 1-6 It is a straight chain alkyl.

[0869] In some embodiments, R 20d is SO2C 3-7 It is a branched alkyl.

[0870] In some embodiments, R 20d is SO2C 3-7 It is cycloalkyl.

[0871] In some embodiments, R 20d is SO2NH2.

[0872] In some embodiments, R 20d is SO2NHR 21 is.

[0873] In some embodiments, R 20d is NHSO2R 22 is.

[0874] In some embodiments, R 20d is -NR 23a R 23b is.

[0875] In some embodiments, R 20d is NHC(O)R 24 is.

[0876] In some embodiments, R 20d is C(O)NHR 24 is.

[0877] In some embodiments, R 20d is C(O)N(R 24 )2.

[0878] In some embodiments, R 20d is a morpholino.

[0879] In some embodiments, R 20d teeth, [ka] is.

[0880] In some embodiments, R 20e is hydrogen.

[0881] In some embodiments, R 20e is -CN.

[0882] In some embodiments, R 20e is -NO2.

[0883] In some embodiments, R 20e is -OH.

[0884] In some embodiments, R 20e is a halogen.

[0885] In some embodiments, R 20e is C 1-6 It is a straight chain alkyl.

[0886] In some embodiments, R 20e is C 3-7 It is a branched alkyl.

[0887] In some embodiments, R 20e is C 3-7 It is cycloalkyl.

[0888] In some embodiments, R 20e is C 1-6 It is a straight chain alkoxy.

[0889] In some embodiments, R 20e is C 3-7 It is a branched alkoxy.

[0890] In some embodiments, R20e is C 3-7 It is cycloalkoxy.

[0891] In some embodiments, R 20e is C 1-6 It is a straight chain haloalkyl.

[0892] In some embodiments, R 20e is C 3-7 It is a branched haloalkyl.

[0893] In some embodiments, R 20e is C 1-6 It is a straight chain haloalkoxy.

[0894] In some embodiments, R 20e is C 3-7 It is a branched haloalkoxy.

[0895] In some embodiments, R 20e is SH.

[0896] In some embodiments, R 20e is SC 1-6 It is a straight chain alkyl.

[0897] In some embodiments, R 20e is SC 3-7 It is a branched alkyl.

[0898] In some embodiments, R 20e is SC 3-7 It is cycloalkyl.

[0899] In some embodiments, R 20e is SO2C 1-6 It is a straight chain alkyl.

[0900] In some embodiments, R 20e is SO2C 3-7 It is a branched alkyl.

[0901] In some embodiments, R 20e is SO2C 3-7 It is cycloalkyl.

[0902] In some embodiments, R 20e is SO2NH2.

[0903] In some embodiments, R 20e is SO2NHR 21 is.

[0904] In some embodiments, R 20e is NHSO2R 22 is.

[0905] In some embodiments, R 20e is -NR 23a R 23b is.

[0906] In some embodiments, R 20e is NHC(O)R 24 is.

[0907] In some embodiments, R 20e is C(O)NHR 24 is.

[0908] In some embodiments, R 20e is C(O)N(R 24 )2.

[0909] In some embodiments, R 20e is a morpholino.

[0910] In some embodiments, R 20e teeth, [ka] is.

[0911] In some embodiments, R 20f is hydrogen.

[0912] In some embodiments, R 20f is -CN.

[0913] In some embodiments, R 20f is -NO2.

[0914] In some embodiments, R 20f is -OH.

[0915] In some embodiments, R 20f is a halogen.

[0916] In some embodiments, R 20f is C 1-6 It is a straight chain alkyl.

[0917] In some embodiments, R 20f is C 3-7 It is a branched alkyl.

[0918] In some embodiments, R 20f is C 3-7 It is cycloalkyl.

[0919] In some embodiments, R 20f is C 1-6 It is a straight chain alkoxy.

[0920] In some embodiments, R 20f is C 3-7 It is a branched alkoxy.

[0921] In some embodiments, R 20f is C 3-7 It is cycloalkoxy.

[0922] In some embodiments, R 20f is C 1-6 It is a straight chain haloalkyl.

[0923] In some embodiments, R 20f is C 3-7It is a branched haloalkyl.

[0924] In some embodiments, R 20f is C 1-6 It is a straight chain haloalkoxy.

[0925] In some embodiments, R 20f is C 3-7 It is a branched haloalkoxy.

[0926] In some embodiments, R 20f is SH.

[0927] In some embodiments, R 20f is SC 1-6 It is a straight chain alkyl.

[0928] In some embodiments, R 20f is SC 3-7 It is a branched alkyl.

[0929] In some embodiments, R 20f is SC 3-7 It is cycloalkyl.

[0930] In some embodiments, R 20f is SO2C 1-6 It is a straight chain alkyl.

[0931] In some embodiments, R 20f is SO2C 3-7 It is a branched alkyl.

[0932] In some embodiments, R 20f is SO2C 3-7 It is cycloalkyl.

[0933] In some embodiments, R 20f is SO2NH2.

[0934] In some embodiments, R 20f is SO2NHR 21 is.

[0935] In some embodiments, R 20f is NHSO2R 22 is.

[0936] In some embodiments, R 20f is -NR 23a R 23b is.

[0937] In some embodiments, R 20f is NHC(O)R 24 is.

[0938] In some embodiments, R 20f is C(O)NHR 24 is.

[0939] In some embodiments, R 20f is C(O)N(R 24 )2.

[0940] In some embodiments, R 20f is a morpholino.

[0941] In some embodiments, R 20f teeth, [ka] is.

[0942] In some embodiments, R 20g is hydrogen.

[0943] In some embodiments, R 20g is -CN.

[0944] In some embodiments, R 20g is -NO2.

[0945] In some embodiments, R 20g is -OH.

[0946] In some embodiments, R 20g is a halogen.

[0947] In some embodiments, R 20g is C 1-6 It is a straight chain alkyl.

[0948] In some embodiments, R 20g is C 3-7 It is a branched alkyl.

[0949] In some embodiments, R 20g is C 3-7 It is cycloalkyl.

[0950] In some embodiments, R 20g is C 1-6 It is a straight chain alkoxy.

[0951] In some embodiments, R 20g is C 3-7 It is a branched alkoxy.

[0952] In some embodiments, R 20g is C 3-7 It is cycloalkoxy.

[0953] In some embodiments, R 20g is C 1-6 It is a straight chain haloalkyl.

[0954] In some embodiments, R 20g is C 3-7 It is a branched haloalkyl.

[0955] In some embodiments, R 20g is C 1-6 It is a straight chain haloalkoxy.

[0956] In some embodiments, R 20g is C 3-7 It is a branched haloalkoxy.

[0957] In some embodiments, R 20g is SH.

[0958] In some embodiments, R 20g is SC 1-6 It is a straight chain alkyl.

[0959] In some embodiments, R 20g is SC 3-7 It is a branched alkyl.

[0960] In some embodiments, R 20g is SC 3-7 It is cycloalkyl.

[0961] In some embodiments, R 20g is SO2C 1-6 It is a straight chain alkyl.

[0962] In some embodiments, R 20g is SO2C 3-7 It is a branched alkyl.

[0963] In some embodiments, R 20g is SO2C 3-7 It is cycloalkyl.

[0964] In some embodiments, R 20g is SO2NH2.

[0965] In some embodiments, R 20g is SO2NHR 21 is.

[0966] In some embodiments, R 20g is NHSO2R 22 is.

[0967] In some embodiments, R 20g is -NR 23a R 23b is.

[0968] In some embodiments, R 20g is NHC(O)R 24 is.

[0969] In some embodiments, R 20g is C(O)NHR 24 is.

[0970] In some embodiments, R 20g is C(O)N(R 24 )2.

[0971] In some embodiments, R 20g is a morpholino.

[0972] In some embodiments, R 20g teeth, [ka] is.

[0973] In some embodiments, R 21 is hydrogen.

[0974] In some embodiments, R 21 is C 1-6 It is a straight chain alkyl.

[0975] In some embodiments, R 21 is C 3-7 It is a branched alkyl.

[0976] In some embodiments, R 21 is C 3-7 It is cycloalkyl.

[0977] In some embodiments, R 22 is hydrogen.

[0978] In some embodiments, R 22 is C 1-6 It is a straight chain alkyl.

[0979] In some embodiments, R 22 is C 3-7 It is a branched alkyl.

[0980] In some embodiments, R 22 is C 3-7 It is cycloalkyl.

[0981] In some embodiments, R 23a is hydrogen.

[0982] In some embodiments, R 23a is C 1-6 It is a straight chain alkyl.

[0983] In some embodiments, R 23a is C 3-7 It is a branched alkyl.

[0984] In some embodiments, R 23a is C 3-7 It is cycloalkyl.

[0985] In some embodiments, R 23b is hydrogen.

[0986] In some embodiments, R 23b is C 1-6 It is a straight chain alkyl.

[0987] In some embodiments, R 23b is C 3-7 It is a branched alkyl.

[0988] In some embodiments, R 23b is C 3-7 It is cycloalkyl.

[0989] In some embodiments, R 24 is hydrogen.

[0990] In some embodiments, R 24 is C 1-6It is a straight chain alkyl.

[0991] In some embodiments, R 24 is C 3-7 It is a branched alkyl.

[0992] In some embodiments, R 24 is C 3-7 It is cycloalkyl.

[0993] In some embodiments, R 25 is hydrogen.

[0994] In some embodiments, R 25 is C 1-6 It is a straight chain alkyl.

[0995] In some embodiments, R 25 is C 3-7 It is a branched alkyl.

[0996] In some embodiments, R 25 is C 3-7 It is cycloalkyl.

[0997] In some embodiments, Q 1 is 1.

[0998] In some embodiments, Q 1 is 2.

[0999] In some embodiments, Q 2 is 1.

[1000] In some embodiments, Q 2 is 2.

[1001] In some embodiments, X 1 , O.

[1002] In some embodiments, X 1 , S.

[1003] In some embodiments, X 1 is SO.

[1004] In some embodiments, X 1 is SO2.

[1005] In some embodiments, X 1 is NR 7 is.

[1006] Exemplary Compounds Exemplary compounds include any of the compounds described herein.In embodiments where the compounds or formulas described herein do not specify the configuration of the lactam stereocenter (i.e., do not show the carbon atom replaced by the lactam nitrogen), the lactam stereocenter may have the R configuration.In other embodiments, the lactam stereocenter may have the S configuration.

[1007] In embodiments, the compound is any compound described herein, or a pharmaceutically acceptable salt thereof. In embodiments, the compound is a compound described in any one of Tables 1-39, or a pharmaceutically acceptable salt thereof. In embodiments, the compound is a compound described in any one of Tables 34-39, or a pharmaceutically acceptable salt thereof.

[1008] Exemplary embodiments include compounds having formula (II), as defined in Table 1 herein below: [ka]

[1009] or a pharmaceutically acceptable salt form thereof. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7]

[1010] Exemplary embodiments include compounds having formula (VIII), as defined in Table 2 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 2-1] [Table 2-2] [Table 2-3]

[1011] Exemplary embodiments include compounds having formula (IX), as defined in Table 3 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 3-1] [Table 3-2] [Table 3-3]

[1012] Exemplary embodiments include compounds having formula (X), as defined in Table 4 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 4-1] [Table 4-2] [Table 4-3]

[1013] Exemplary embodiments include compounds having formula (XI), as defined in Table 5 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 5-1] [Table 5-2] [Table 5-3]

[1014] Exemplary embodiments include compounds having formula (XII), as defined in Table 6 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4] [Table 6-5] [Table 6-6] [Table 6-7]

[1015] Exemplary embodiments include compounds having formula (XIII), as defined in Table 7 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 7-1] [Table 7-2] [Table 7-3]

[1016] Exemplary embodiments include compounds having formula (XIV), as defined in Table 8 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 8-1] [Table 8-2] [Table 8-3]

[1017] Exemplary embodiments include compounds having formula (XV), as defined in Table 9 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 9-1] [Table 9-2] [Table 9-3]

[1018] Exemplary embodiments include compounds having formula (XVI), as defined in Table 10 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 10-1] [Table 10-2] [Table 10-3]

[1019] Exemplary embodiments include compounds having formula (XVII), as defined in Table 11 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 11-1] [Table 11-2] [Table 11-3] [Table 11-4] [Table 11-5] [Table 11-6]

[1020] Exemplary embodiments include compounds having formula (XVIII), as defined in Table 12 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 12-1] [Table 12-2] [Table 12-3]

[1021] Exemplary embodiments include compounds having formula (XIX), as defined in Table 13 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 13-1] [Table 13-2] [Table 13-3]

[1022] Exemplary embodiments include compounds having formula (XX), as defined in Table 14 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 14-1] [Table 14-2] [Table 14-3]

[1023] Exemplary embodiments include compounds having formula (XXI), as defined in Table 15 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 15-1] [Table 15-2] [Table 15-3]

[1024] Exemplary embodiments include compounds having formula (XXII), as defined in Table 16 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 16-1]

Table 16-2

Table 16-3

Table 16-4

Table 16-5

Table 16-6

Table 16-7

Table 16-8

Table 16-9

Table 16-10

Table 16-11

Table 16-12

Table 16-13

Table 16-14

Table 16-15

Table 16-16

Table 16-17

Table 16-18

[1025] Exemplary embodiments include compounds having formula (XXIII), as defined in Table 17 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 17-1] [Table 17-2] [Table 17-3] [Table 17-4] [Table 17-5] [Table 17-6] [Table 17-7] [Table 17-8]

Table 17-9

Table 17-10

Table 17-11

Table 17-12

Table 17-13

Table 17-14

Table 17-15

Table 17-16

Table 17-17

Table 17-18

Table 17-19

Table 17-20

Table 17-21

Table 17-22

Table 17-23

Table 17-24

[1026] Exemplary embodiments include compounds having formula (XXIV), as defined in Table 18 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 18-1] [Table 18-2] [Table 18-3] [Table 18-4] [Table 18-5] [Table 18-6] [Table 18-7] [Table 18-8] [Table 18-9] [Table 18-10] [Table 18-11] [Table 18-12] [Table 18-13] [Table 18-14] [Table 18-15] [Table 18-16] [Table 18-17] [Table 18-18] [Table 18-19] [Table 18-20] [Table 18-21] [Table 18-22] [Table 18-23] [Table 18-24] [Table 18-25]

[1027] Exemplary embodiments include compounds having formula (XXV), as defined in Table 19 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 19-1]

Table 19-2

Table 19-3

Table 19-4

Table 19-5

Table 19-6

Table 19-7

Table 19-8

Table 19-9

Table 19-10

Table 19-11

Table 19-12

Table 19-13

Table 19-14

Table 19-15

Table 19-16

Table 19-17

Table 19-18

[1028] Exemplary embodiments include compounds having formula (XXVI), as defined in Table 20 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 20-1]

Table 20-2

Table 20-3

Table 20-4

Table 20-5

Table 20-6

Table 20-7

Table 20-8

Table 20-9

Table 20-10

Table 20-11

Table 20-12

Table 20-13

Table 20-14

Table 20-15

Table 20-16

Table 20-17

[1029] Exemplary embodiments include compounds having formula (XXVII), as defined in Table 21 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 21-1] [Table 21-2] [Table 21-3] [Table 21-4] [Table 21-5] [Table 21-6] [Table 21-7] [Table 21-8] [Table 21-9] [Table 21-10] [Table 21-11] [Table 21-12] [Table 21-13] [Table 21-14] [Table 21-15] [Table 21-16] [Table 21-17] [Table 21-18] [Table 21-19] [Table 21-20] [Table 21-21] [Table 21-22] [Table 21-23] [Table 21-24] [Table 21-25] [Table 21-26] [Table 21-27] [Table 21-28] [Table 21-29] [Table 21-30]

[1030] Exemplary embodiments include compounds having formula (XXVIII), as defined in Table 22 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 22-1] [Table 22-2] [Table 22-3] [Table 22-4] [Table 22-5] [Table 22-6] [Table 22-7] [Table 22-8] [Table 22-9] [Table 22-10] [Table 22-11] [Table 22-12] [Table 22-13] [Table 22-14] [Table 22-15] [Table 22-16] [Table 22-17] [Table 22-18] [Table 22-19] [Table 22-20] [Table 22-21] [Table 22-22] [Table 22-23] [Table 22-24] [Table 22-25] [Table 22-26] [Table 22-27] [Table 22-28] [Table 22-29] [Table 22-30] [Table 22-31]

[1031] Exemplary embodiments include compounds having formula (XXIX), as defined in Table 23 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 23-1] [Table 23-2] [Table 23-3] [Table 23-4] [Table 23-5] [Table 23-6] [Table 23-7] [Table 23-8] [Table 23-9] [Table 23-10] [Table 23-11] [Table 23-12] [Table 23-13] [Table 23-14] [Table 23-15] [Table 23-16]

Table 23-17

Table 23-18

Table 23-19

Table 23-20

Table 23-21

Table 23-22

Table 23-23

Table 23-24

Table 23-25

Table 23-26

Table 23-27

Table 23-28

Table 23-29

Table 23-30

Table 23-31

[1032] Exemplary embodiments include compounds having formula (XXX), as defined in Table 24 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 24-1] [Table 24-2] [Table 24-3] [Table 24-4] [Table 24-5] [Table 24-6] [Table 24-7] [Table 24-8] [Table 24-9] [Table 24-10] [Table 24-11] [Table 24-12] [Table 24-13] [Table 24-14]

Table 24-15

Table 24-16

Table 24-17

Table 24-18

Table 24-19

Table 24-20

Table 24-21

Table 24-22

Table 24-23

Table 24-24

Table 24-25

Table 24-26

Table 24-27

Table 24-28

Table 24-29

Table 24-30

Table 24-31

[1033] Exemplary embodiments include compounds having formula (XXXI), as defined in Table 25 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 25-1] [Table 25-2] [Table 25-3] [Table 25-4] [Table 25-5] [Table 25-6] [Table 25-7] [Table 25-8] [Table 25-9] [Table 25-10] [Table 25-11] [Table 25-12] [Table 25-13] [Table 25-14] [Table 25-15] [Table 25-16]

[1034] Exemplary embodiments include compounds having formula (XXXII), as defined in Table 26 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 26-1] [Table 26-2] [Table 26-3] [Table 26-4] [Table 26-5] [Table 26-6] [Table 26-7] [Table 26-8] [Table 26-9] [Table 26-10] [Table 26-11] [Table 26-12] [Table 26-13] [Table 26-14] [Table 26-15] [Table 26-16] [Table 26-17]

[1035] Exemplary embodiments include compounds having formula (XXXIV), as defined in Table 27 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 27-1] [Table 27-2] [Table 27-3] [Table 27-4] [Table 27-5] [Table 27-6] [Table 27-7] [Table 27-8] [Table 27-9] [Table 27-10] [Table 27-11] [Table 27-12] [Table 27-13] [Table 27-14] [Table 27-15] [Table 27-16] [Table 27-17]

[1036] Exemplary embodiments include compounds having formula (XXXV), as defined in Table 28 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 28-1] [Table 28-2] [Table 28-3] [Table 28-4] [Table 28-5] [Table 28-6] [Table 28-7] [Table 28-8] [Table 28-9] [Table 28-10] [Table 28-11]

[1037] Exemplary embodiments include compounds having formula (XXXVI), as defined in Table 29 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 29-1] [Table 29-2] [Table 29-3] [Table 29-4] [Table 29-5] [Table 29-6] [Table 29-7] [Table 29-8] [Table 29-9] [Table 29-10] [Table 29-11]

[1038] Exemplary embodiments include compounds having formula (XXXVII), as defined in Table 30 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 30-1] [Table 30-2] [Table 30-3] [Table 30-4] [Table 30-5] [Table 30-6] [Table 30-7] [Table 30-8] [Table 30-9] [Table 30-10]

[1039] Exemplary embodiments include compounds having formula (XXXVIII), as defined in Table 31 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 31-1] [Table 31-2] [Table 31-3] [Table 31-4] [Table 31-5] [Table 31-6] [Table 31-7] [Table 31-8] [Table 31-9] [Table 31-10] [Table 31-11] [Table 31-12] [Table 31-13]

Table 31-14

Table 31-15

Table 31-16

Table 31-17

Table 31-18

Table 31-19

Table 31-20

Table 31-21

Table 31-22

Table 31-23

Table 31-24

Table 31-25

Table 31-26

Table 31-27

Table 31-28

Table 31-29

Table 31-30

Table 31-31

Table 31-32

Table 31-33

Table 31-34

Table 31-35

Table 31-36

Table 31-37

Table 31-38

Table 31-39

Table 31-40

Table 31-41

Table 31-42

Table 31-43

Table 31-44

Table 31-45

Table 31-46

[1040] Exemplary embodiments include compounds having formula (XXXIX), as defined in Table 32 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 32-1] [Table 32-2] [Table 32-3] [Table 32-4] [Table 32-5] [Table 32-6] [Table 32-7] [Table 32-8] [Table 32-9] [Table 32-10] [Table 32-11] [Table 32-12] [Table 32-13] [Table 32-14] [Table 32-15] [Table 32-16]

Table 32-17

Table 32-18

Table 32-19

Table 32-20

Table 32-21

Table 32-22

Table 32-23

Table 32-24

Table 32-25

Table 32-26

Table 32-27

Table 32-28

Table 32-29

Table 32-30

Table 32-31

Table 32-32

Table 32-33

Table 32-34

Table 32-35

Table 32-36

Table 32-37

Table 32-38

Table 32-39

Table 32-40

Table 32-41

Table 32-42

Table 32-43

Table 32-44

Table 32-45

Table 32-46

Table 32-47

Table 32-48

Table 32-49

[1041] Exemplary embodiments include compounds having the formula (XXXX), as defined in Table 33 herein below: [ka] or a pharmaceutically acceptable salt form thereof. [Table 33-1] [Table 33-2]

Table 33-3

Table 33-4

Table 33-5

Table 33-6

Table 33-7

Table 33-8

Table 33-9

Table 33-10

Table 33-11

Table 33-12

Table 33-13

Table 33-14

Table 33-15

Table 33-16

Table 33-17

Table 33-18

Table 33-19

Table 33-20

Table 33-21

Table 33-22

Table 33-23

Table 33-24

Table 33-25

Table 33-26

Table 33-27

Table 33-28

Table 33-29

Table 33-30

Table 33-31

Table 33-32

Table 33-33

Table 33-34

Table 33-35

Table 33-36

Table 33-37

Table 33-38

Table 33-39

Table 33-40

Table 33-41

Table 33-42

Table 33-43

Table 33-44

Table 33-45

Table 33-46

Table 33-47

Table 33-48

Table 33-49

Table 33-50

Table 33-51

Table 33-52

[1042] For purposes of illustrating the manner in which compounds of the present invention are named and designated herein, compounds of the formula: [ka] The compound having the chemical name 8-(methylsulfonyl)-3-(2-(4-phenylpiperazin-1-yl)ethyl)-2,8-diazaspiro[4.5]decan-1-one.

[1043] For purposes of illustrating the manner in which compounds of the present invention are named and designated herein, compounds of the formula: [ka] The compound having the chemical name 8-(methylsulfonyl)-3-(2-(5-phenylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)ethyl)-2,8-diazaspiro[4.5]decan-1-one.

[1044] For purposes of illustrating the manner in which compounds of the present invention are named and designated herein, compounds of the formula: [ka]

[1045] The compound having the chemical name 8-(methylsulfonyl)-3-(2-(4-phenylpiperazin-1-yl)ethyl)-2,8-diazaspiro[4.5]decan-1-one.

[1046] For purposes of the present invention, for example, a compound represented by the following racemic formula: [ka] formula: [ka] Or the expression: [ka] Either of the two enantiomers having the formula: or a mixture thereof, or, if a second chiral center is present, all diastereomers, are equally well represented.

[1047] In all of the embodiments provided herein, the examples of suitable optional substituents are not intended to limit the scope of the claims of the present invention. The compounds of the present invention can contain any of the substituents or combinations of substituents provided herein.

[1048] Process for preparing the 5-hydroxytryptamine receptor 7 activity modulator of the present invention The present invention further relates to a process for preparing the 5-hydroxytryptamine receptor 7 activity modulators of the present invention.

[1049] The compounds of the present teachings can be prepared according to the procedures outlined herein from commercially available starting materials, compounds known in the literature, or readily prepared intermediates using standard synthetic methods and procedures known to those skilled in the art. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be readily obtained from the relevant scientific literature or from standard textbooks in the field. Where typical or preferred process conditions (i.e., reaction temperatures, times, molar ratios of reactants, solvents, pressures, etc.) are given, it will be understood that other process conditions can also be used unless otherwise specified. Optimum reaction conditions may vary with the particular reactants or solvents used, but such conditions can be determined by one skilled in the art by routine optimization procedures. Those skilled in the art of organic synthesis will recognize that the nature and order of the synthetic steps presented can be varied for the purpose of optimizing the formation of the compounds described herein.

[1050] The processes described herein can be monitored according to any suitable method known in the art. For example, product formation can be monitored by nuclear magnetic resonance spectroscopy (e.g., 1 H or 13 C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry, etc. Monitoring can be by optical means or by chromatography, such as high pressure liquid chromatography (HPLC), gas chromatography (GC), gel permeation chromatography (GPC), or thin layer chromatography (TLC).

[1051] The preparation of compounds may involve the protection and deprotection of various chemical groups.The need for protection and deprotection and the selection of appropriate protecting groups can be easily determined by those skilled in the art.Protective group chemistry can be found, for example, in Greene et al., Protective Groups in Organic Synthesis, 2d.Ed. (Wiley & Sons, 1991), the entire disclosure of which is incorporated herein by reference for all purposes.

[1052] The reactions or processes described herein can be carried out in a suitable solvent, which can be easily selected by those skilled in the art of organic synthesis.Suitable solvents are typically substantially non-reactive with the reactants, intermediates, and / or products at the temperature at which the reaction is carried out, i.e., at temperatures ranging from the freezing temperature of the solvent to the boiling temperature of the solvent.A given reaction can be carried out in one solvent or in a mixture of two or more solvents.A suitable solvent for a particular reaction step can be selected depending on the particular reaction step.

[1053] The compounds of these teachings can be prepared by methods known in the art of organic chemistry. The reagents used in preparing the compounds of these teachings are either commercially available or can be prepared by standard procedures described in the literature. For example, the compounds of the present invention can be prepared according to the methods illustrated in the general synthetic schemes.

[1054] General synthetic scheme for the preparation of compounds The reagents used in preparing the compounds of the present invention are either commercially available or can be prepared by standard procedures described in the literature. According to the present invention, this class of compounds can be produced by one of the following reaction schemes. Thus, the present invention further features any of the synthetic intermediates or processes described herein.

[1055] Compounds of the present disclosure can be prepared according to the processes outlined in Schemes 1-1. [ka]

[1056] A suitably substituted compound of formula (1), known compound, or compound prepared by known methods, wherein PG is a protection selected from the group consisting of benzyl, tert-butyl carbonate, benzyl carbonate, and tert-butyldimethylsilyl, is reacted with a compound of formula (2), known compound, or compound prepared by known methods, in the presence of BnNEt3Cl in the presence of a base such as potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, cesium hydroxide, lithium hydroxide, in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, methanol, ethanol, isopropanol, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, optionally with heating, optionally with microwave irradiation, to give a compound of formula (2), known compound, or compound prepared by known methods The compound of formula (3) is heated in the presence of a base such as pyridine, 2,6-dimethylpyridine, 2,6-di-tert-butylpyridine, triethylamine, diisopropylethylamine, and the like in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and the like, optionally with microwave irradiation, to give a compound of formula (4), a known compound, or a compound prepared by a known method, wherein Z 1is reacted with a compound selected from the group consisting of methyl, trifluoromethyl, para-tolyl, and para-NO2-phenyl to provide a compound of formula (5). The compound of formula (5) is reacted with a base such as potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, and the like in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and the like, optionally with heating, and optionally with microwave irradiation, to provide a compound of formula (6). [ka]

[1057] The compound of formula (6) is reacted with a compound of formula (7), a known compound, or a compound prepared by known methods, in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, lithium hydride, and the like, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, and the like, optionally with heating, optionally using microwave irradiation, to provide a compound of formula (8). The compound of formula (8) is reacted with an acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, para-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and the like in a solvent such as benzene, toluene, para-xylylene, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, and the like, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (9). The compound of formula (9) is reacted with a compound of formula (10), a known compound, or a compound prepared by known methods, wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsulfonate, in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, lithium hydride, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, and the like, optionally with heating, optionally using microwave irradiation, to provide a compound of formula (11). [ka]

[1058] The compound of formula (11) is reacted with sodium in the presence of naphthalene in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (12). The compound of formula (12) is reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, or N,N-dimethylformamide, optionally with heating, to provide a compound of formula (13). Alternatively, the compound of formula (12) is reacted with an acid such as trifluoroacetic acid, hydrochloric acid, or sulfuric acid in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (13). Alternatively, the compound of formula (12) is reacted with tetrabutylammonium fluoride in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (13). Compound (13) is reacted with carbon tetrabromide in the presence of triphenylphosphine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with microwave irradiation and optionally with heating, to provide compounds of formula (14).The compound of formula (14) is reacted with a compound of formula (15), a known compound, or a compound prepared by known methods, in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and the like, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (16). [ka]

[1059] The compound of formula (6) is reacted with a compound of formula (17), a known compound, or a compound prepared by known methods, in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, lithium hydride, and the like, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, and the like, optionally with heating, optionally using microwave irradiation, to provide a compound of formula (18). Compounds of formula (18) can be reacted with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, para-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and the like in solvents such as benzene, toluene, para-xylylene, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and the like, optionally with heating, and optionally with microwave irradiation. The compound of formula (19) is reacted with a compound of formula (20), a known compound, or a compound prepared by a known method, wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsulfonate, in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating, optionally using microwave irradiation, to obtain a compound of formula (21). The compound of formula (21) is reacted with a compound of formula (22), a known compound, or a compound prepared by known methods, wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsulfonate, in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, lithium hydride, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, and the like, optionally with heating, optionally with microwave irradiation, to provide a compound of formula (11). [ka]

[1060] Compounds of formula (19) can be heated in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, lithium hydride, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, and the like, optionally with microwave irradiation, to produce compounds of formula (23), known compounds, or compounds prepared by known methods, wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolyl sulfonate, and Q is 1 is selected from the group consisting of 1 and 2) to obtain a compound of formula (24). The compound of formula (24) is reacted with a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, lithium hydride, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, and the like, optionally with heating, optionally with microwave irradiation, to obtain a compound of formula (25), a known compound, or a compound prepared by known methods, wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolyl sulfonate, and Q 2 is selected from the group consisting of 1 and 2) to obtain a compound of formula (26). The compound of formula (26) is reacted with benzylidene-bis(tricyclohexylphosphine)dichlororuthenium, (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine), optionally heated in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, and the like, optionally with microwave irradiation, to obtain a compound of formula (26). dichloro(2-isopropoxyphenylmethylene)(tricyclohexylphosphine)ruthenium(II), [1,3-bis(2-methylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(o-isopropoxyphenylmethylene)ruthenium dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-methyl-2-butenylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-dimesityl-2-imidazolidinylidene]dichloro[3-(2-pyridinyl)propylidene]ruthenium(II), dichloro ruthenium(II), dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), dichloro(tricyclohexylphosphine)[(tricyclohexylphosphoranyl)methylidene]ruthenium tetrafluoroborate, dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][(tricyclohexylphosphoranyl)methylidene]ruthenium(II) tetrafluoroborate, [2-(1-methylethoxy-O)phenylmethyl-C](nitrilo tri-O,O'){rel-(2R,5R,7R)-adamantan-2,1-diyl[3-(2,4,6-trimethylphenyl)-1-imidazolidinyl-2-ylidene]}ruthenium, dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II), [1,3-bis(2-methylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2,4,Reaction with a ruthenium catalyst such as [6-trimethylphenyl]-2-imidazolidinylidene][3-(2-pyridinyl)propylidene]ruthenium(II) gives a compound of formula (27). [ka]

[1061] Compounds of formula (27) are reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide compounds of formula (28). Compounds of formula (28) can be reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, or N,N-dimethylformamide, optionally with heating, to provide compounds of formula (29). Alternatively, compounds of formula (28) can be reacted with hydrogen gas in an organic solvent, such as tetrahydrofuran, 1,4-dioxane, methylene chloride, or 1,2-dichloroethane, optionally with heating. Reaction with an acid such as trifluoroacetic acid, hydrochloric acid, or sulfuric acid in a solvent such as ethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with microwave irradiation and optionally with heating, provides a compound of formula (29). Alternatively, reaction of compound of formula (28) with tetrabutylammonium fluoride in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with microwave irradiation and optionally with heating, provides a compound of formula (29). Compounds of formula (29) are reacted with sodium in the presence of naphthalene in solvents such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, and the like, optionally with microwave irradiation and optionally with heating, to provide compounds of formula (30). [ka]

[1062] Alternatively, the compound of formula (27) can be reacted with sodium in the presence of naphthalene in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (31). The compound of formula (31) can be reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, or N,N-dimethylformamide, optionally with heating, to provide a compound of formula (32). The compound of formula (32) is reacted with hydrogen gas in the presence of a palladium catalyst such as palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II) in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide the compound of formula (30). Alternatively, the compound of formula (32) is reacted with an acid such as trifluoroacetic acid, hydrochloric acid, sulfuric acid, and the like in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with microwave irradiation and optionally with heating, to provide the compound of formula (30).Alternatively, the compound of formula (32) is reacted with tetrabutylammonium fluoride in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with microwave irradiation and optionally with heating, to provide the compound of formula (30). [ka]

[1063] Compound (30) is reacted with carbon tetrabromide in the presence of triphenylphosphine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with microwave irradiation and optionally with heating, to provide compounds of formula (33). The compound of formula (33) is reacted with a compound of formula (34), a known compound, or a compound prepared by known methods, in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and the like, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (35). [ka]

[1064] Compounds of formula (31) are reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide compounds of formula (36). Alternatively, the compound of formula (31) is reacted with an acid such as trifluoroacetic acid, hydrochloric acid, or sulfuric acid in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (36). Alternatively, the compound of formula (31) is reacted with tetrabutylammonium fluoride in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with microwave irradiation and optionally with heating, to provide a compound of formula (36). Compound (36) is reacted with carbon tetrabromide in the presence of triphenylphosphine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with microwave irradiation and optionally with heating, to give compounds of formula (37). The compound is reacted with a compound of formula (38), a known compound, or a compound prepared by known methods, in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and the like, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with heating, optionally using microwave irradiation, to provide a compound of formula (39). [ka]

[1065] The compound of formula (26) is reacted with a compound of formula ozone in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation. The resulting material is then treated with triphenylphosphine in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, to provide a compound of formula (40). Alternatively, a compound of formula (26) is reacted with a compound of formula ozone in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation. The resulting material is then treated with dimethyl sulfide in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, to provide a compound of formula (40). Alternatively, the compound of formula (26) is reacted with ruthenium chloride in the presence of sodium periodate in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2...

Claims

[Claim 1] The invention described in the specification.

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