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Title:
LYSYL OXIDASE-LIKE 2 INHIBITORS FOR THE TREATMENT OF INFLAMMATORY CONDITIONS
Document Type and Number:
WIPO Patent Application WO/2017/197088
Kind Code:
A1
Abstract:
Described herein are methods of using LOXL2 inhibitor compounds for the treatment of autoimmune diseases or conditions or inflammatory diseases or conditions in a mammal. Also disclosed are methods for reducing LOXL2 activity in a mammal with an autoimmune disease or condition or an inflammatory disease or condition.

Inventors:
BAIN GRETCHEN (US)
ROWBOTTOM MARTIN W (US)
HUTCHINSON JOHN HOWARD (US)
Application Number:
PCT/US2017/032115
Publication Date:
November 16, 2017
Filing Date:
May 11, 2017
Export Citation:
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Assignee:
PHARMAKEA INC (US)
International Classes:
A61K31/44; A61K31/137; A61K31/165; C07D213/16; C07D401/06; C07D401/12; C07D405/06; C07D405/12
Domestic Patent References:
WO2009035791A12009-03-19
Other References:
BERTINI, V ET AL.: "Alkylamino Derivatives of 4_aminomethylpyridine as Inhibitors of Copper-Containing Amine Oxidases", J. MED. CHEM., vol. 48, no. 3, 2005, pages 664 - 670, XP055439097
CSISZAR K: "Lysyl Oxidases: A Novel Multifunctional Amine Oxidase Family", PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, vol. 70, 2001, pages 1 - 32, XP009024882, DOI: doi:10.1016/S0079-6603(01)70012-8
Attorney, Agent or Firm:
HOSTETLER, Michael J. (650 Page Mill RoadPalo Alto, California, US)
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Claims:
CLAIMS

WHAT IS CLAIMED IS:

1. A method of treating an autoimmune disease or condition or an inflammatory disease or condition in a mammal comprising administering a Lysyl oxidase like-2 (LOXL2) inhibitor compound to the mammal, wherein the LOXL2 inhibitor compound is a substituted or unsubstituted arylmethylamine compound or a substituted or unsubstituted heterocyclylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

2. The method of claim 1, wherein the autoimmune disease or condition is rheumatoid

arthritis, juvenile idiopathic arthritis, psoriatic arthritis, osteoarthritis, Still's disease, lupus, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Ord's thyroiditis, Graves' disease Sjogren's syndrome, multiple sclerosis, Guillain-Barre syndrome, acute disseminated encephalomyelitis, Addison's disease, opsoclonus-myoclonus syndrome, ankylosing spondylitis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hepatitis, coeliac disease, Goodpasture's syndrome, idiopathic

thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Reiter's syndrome, Takayasu's arteritis, temporal arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia universalis, Behcet's disease, chronic fatigue, dysautonomia, endometriosis, interstitial cystitis, neuromyotonia, scleroderma, or vulvodynia.

3. The method of claim 1, wherein the autoimmune disease or condition is rheumatoid

arthritis, juvenile idiopathic arthritis, psoriatic arthritis, osteoarthritis, or ankylosing spondylitis.

4. The method of claim 1, wherein the inflammatory disease or condition is asthma,

inflammatory bowel disease, appendicitis, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, colitis, conjunctivitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, hepatitis, hidradenitis suppurativa, laryngitis, mastitis, meningitis, myelitis myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonitis, pneumonia, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, uveitis, vaginitis, vasculitis, or vulvitis.

5. The method of any one of claims 1-4, wherein the LOXL2 inhibitor is administered to the mammal by oral administration, intravenous administration, subcutaneous administration, inhalation, nasal administration, dermal administration, or ophthalmic administration.

6. The method of any one of claims 1-4, wherein the LOXL2 inhibitor is administered to the mammal in the form of a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion.

7. The method of any one of claims 1-6, wherein the LOXL2 inhibitor is a substituted or unsubstituted phenylmethylamine compound, or a substituted or unsubstituted

naphthylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

8. The method of any one of claims 1-6, wherein the LOXL2 inhibitor is a substituted or unsubstituted heterocyclylcompound, or a pharmaceutically acceptable salt, or solvate thereof.

9. The method of any one of claims 1-6, wherein the LOXL2 inhibitor is a substituted or unsubstituted heteroarylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

10. The method of any one of claims 1-6, wherein the LOXL2 inhibitor is a substituted or unsubstituted (monocyclic heteroaryl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

11. The method of claim 10, wherein the monocyclic heteroaryl is a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl.

12. The method of claim 10 or claim 11, wherein the monocyclic heteroaryl is a 5-membered monocyclic heteroaryl that is imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, oxadiazolyl, thiadiazolyl, or furazanyl.

13. The method of claim 10 or claim 11, wherein the monocyclic heteroaryl is a 6-membered monocyclic heteroaryl that is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl.

14. The method of any one of claims 1-6, wherein the LOXL2 inhibitor is a substituted or unsubstituted (bicyclic heteroaryl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

15. The method of claim 14, wherein the bicyclic heteroaryl is indolizinyl, indolyl,

benzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8- naphthyridinyl, or pteridinyl.

16. The method of any one of claims 1-6, wherein the LOXL2 inhibitor is a substituted or unsubstituted (bicyclic heterocyclyl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

17. The method of claim 16, wherein the bicyclic heterocyclyl is quinolinone, isoquinolinone, chromone, or coumarin.

18. The method of any one of claims 1-17, wherein the LOXL2 inhibitor is administered to the mammal on a continuous dosing schedule.

19. The method of any one of claims 1-17, wherein the LOXL2 inhibitor is administered to the mammal on a continuous daily dosing schedule.

20. The method of any one of claims 1-17, wherein the LOXL2 inhibitor is administered to the mammal once a day, twice a day, three times a day, four times a day, five times a day, or six times a day.

21. The method of any one of claims 1-20, wherein the method further comprises

administration of one or more additional therapeutic agents to the mammal.

Description:
LYSYL OXIDASE-LIKE 2 INHIBITORS FOR THE TREATMENT OF

INFLAMMATORY CONDITIONS

CROSS-REFERENCE

[0001] This application claims benefit of U.S. Provisional Patent Application No. 62/335,263, filed on May 12, 2016, which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

[0002] Described herein are compounds that are lysyl oxidase-like 2 (LOXL2) inhibitors, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of autoimmune diseases or conditions or inflammatory diseases or conditions.

BACKGROUND OF THE INVENTION

[0003] Lysyl oxidase like-2 (LOXL2) is an amine oxidase enzyme that catalyzes crosslinking of extracellular matrix proteins. LOXL2 is also involved in intracellular processes such as mediating epithelial-to-mesenchymal transition of cells. LOXL2 signaling is implicated in, for example, fibrotic diseases, cancer and rheumatoid arthritis.

SUMMARY OF THE INVENTION

[0004] In one aspect, described herein are LOXL2 inhibitors and uses thereof. In some embodiments, the LOXL2 inhibitors described herein have the structure of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof.

[0005] In one aspect, described herein is a method of treating a disease or condition in a mammal that benefits from the inhibition or reduction of Lysyl oxidase like-2 (LOXL2) activity comprising administering a LOXL2 inhibitor compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, to the mammal in need thereof. In some embodiments, the disease or condition is an autoimmune disease or condition. In some embodiments, the disease or condition is an inflammatory disease or condition.

[0006] In one aspect, described herein is a method of treating an auotimmune disease or condition or an inflammatory disease or condition in a mammal comprising administering a Lysyl oxidase like-2 (LOXL2) inhibitor compound to the mammal, wherein the LOXL2 inhibitor compound is a substituted or unsubstituted arylmethylamine compound or a substituted or unsubstituted heterocyclylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. [0007] In some embodiments, the auotimmune disease or condition is rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, osteoarthritis, Still's disease, lupus, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Ord's thyroiditis, Graves' disease Sjogren's syndrome, multiple sclerosis, Guillain-Barre syndrome, acute disseminated encephalomyelitis, Addison's disease, opsoclonus-myoclonus syndrome, ankylosing spondylitis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hepatitis, coeliac disease, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Reiter's syndrome, Takayasu's arteritis, temporal arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia universalis, Behcet's disease, chronic fatigue, dysautonomia, endometriosis, interstitial cystitis, neuromyotonia, scleroderma, or vulvodynia.

[0008] In some embodiments, the autoimmune disease or condition is rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, osteoarthritis, or ankylosing spondylitis.

[0009] In some embodiments, the inflammatory disease or condition is asthma, inflammatory bowel disease, appendicitis, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, colitis, conjunctivitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, hepatitis, hidradenitis suppurativa, laryngitis, mastitis, meningitis, myelitis myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonitis, pneumonia, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, uveitis, vaginitis, vasculitis, or vulvitis.

[0010] In some embodiments, the LOXL2 inhibitor is administered to the mammal by oral administration, intravenous administration, subcutaneous administration, inhalation, nasal administration, dermal administration, or ophthalmic administration.

[0011] In some embodiments, the LOXL2 inhibitor is administered to the mammal in the form of a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion.

[0012] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted

phenylmethylamine compound, or a substituted or unsubstituted naphthylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

[0013] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted

heterocyclyl compound, or a pharmaceutically acceptable salt, or solvate thereof.

[0014] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted

heteroarylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. [0015] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted

(monocyclic heteroaryl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

[0016] In some embodiments, the monocyclic heteroaryl is a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl.

[0017] In some embodiments, the monocyclic heteroaryl is a 5-membered monocyclic heteroaryl that is imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, oxadiazolyl, thiadiazolyl, or furazanyl.

[0018] In some embodiments, the monocyclic heteroaryl is a 6-membered monocyclic heteroaryl that is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl.

[0019] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted (bicyclic heteroaryl)methyl amine compound, or a pharmaceutically acceptable salt, or solvate thereof.

[0020] In some embodiments, the bicyclic heteroaryl is indolizinyl, indolyl, benzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, or pteridinyl.

[0021] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted (bicyclic heterocyclyl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

[0022] In some embodiments, the bicyclic heterocyclyl is quinolinone, isoquinolinone, chromone, or coumarin.

[0023] In some embodiments, the LOXL2 inhibitor is administered to the mammal on a continuous dosing schedule.

[0024] In some embodiments, the LOXL2 inhibitor is administered to the mammal on a continuous daily dosing schedule.

[0025] In some embodiments, the LOXL2 inhibitor is administered to the mammal once a day, twice a day, three times a day, four times a day, five times a day, or six times a day.

[0026] In some embodiments, the method further comprises administration of one or more additional therapeutic agents to the mammal.

[0027] In one aspect, described herein is a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, and at least one pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by intravenous administration, subcutaneous administration, oral administration, inhalation, nasal administration, dermal administration, or ophthalmic administration. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by intravenous administration, subcutaneous administration, or oral administration. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by oral administration. In some embodiments, the pharmaceutical composition is in the form of a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion. In some embodiments, the pharmaceutical composition is in the form of a tablet, a pill, or a capsule.

[0028] In one aspect, described herein is a method of treating or preventing any one of the diseases or conditions described herein comprising administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, to a mammal in need thereof.

[0029] In any of the aforementioned aspects are further embodiments in which the effective amount of the compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is: (a) systemically administered to the mammal; and/or (b) administered orally to the mammal; and/or (c) intravenously administered to the mammal; and/or (d) administered by inhalation; and/or (e) t administered by nasal administration; or and/or (f) administered by injection to the mammal; and/or (g) administered topically to the mammal; and/or (h)

administered by ophthalmic administration; and/or (i) administered rectally to the mammal;

and/or (j) administered non-systemically or locally to the mammal.

[0030] In any of the aforementioned aspects are further embodiments comprising single administrations of the effective amount of the compound, including further embodiments in which the compound is administered once a day to the mammal or the compound is administered to the mammal multiple times over the span of one day. In some embodiments, the compound is administered on a continuous dosing schedule. In some embodiments, the compound is administered on a continuous daily dosing schedule.

[0031] In any of the aforementioned aspects involving the treatment of a disease or condition are further embodiments comprising administering at least one additional agent in addition to the administration of a LOXL2 inhibitor compound, or a pharmaceutically acceptable salt, or solvate thereof. In various embodiments, each agent is administered in any order, including

simultaneously.

[0032] In any of the embodiments disclosed herein, the mammal is a human.

[0033] In some embodiments, compounds provided herein are administered to a human.

[0034] In some embodiments, compounds provided herein are orally administered.

[0035] Articles of manufacture, which include packaging material, a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, within the packaging material, and a label that indicates that the compound or composition, or a pharmaceutically acceptable salt, pharmaceutically active metabolite, pharmaceutically acceptable prodrug, or a

pharmaceutically acceptable solvate thereof, is used for inhibiting the activity of LOXL2, or for the treatment, prevention or amelioration of one or more symptoms of a disease or condition that would benefit from inhibition or reduction of the LOXL2 activity, are provided.

[0036] Other objects, features and advantages of the compounds, methods and compositions described herein will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments, are given by way of illustration only, since various changes and modifications within the spirit and scope of the instant disclosure will become apparent to those skilled in the art from this detailed description.

DETAILED DESCRIPTION OF THE INVENTION

[0037] Lysyl oxidase like-2 (LOXL2) is a member of the lysyl oxidase (LOX) family, which comprises Cu 2+ and lysine tyrosylquinone (LTQ)-dependent amine oxidases. The family comprises five genes: lox (LOX), /ox/7 (lysyl oxidase like-1, LOXL1), loxl2 (LOXL2), loxl3 (lysyl oxidase like-3, LOXL3), and loxl4 (lysyl oxidase like-4, LOXL4). The LOX family is known for catalyzing the oxidative deamination of the ε-amino group of lysines and

hydroxylysines in collagen and elastin to promote crosslinking of these molecules. Crosslinking of collagen and elastin is essential for maintaining tensile strength of the extracellular matrix.

[0038] LOXL2 has been demonstrated to have intracellular functions aside from its role in remodeling of the extracellular matrix. LOXL2 positively regulates the epithelial-to- mesenchymal transition (EMT) transducer, Snail 1, by promoting Snail 1 stability and functional activity. LOXL2 contributes positively to the activation of the focal adhesion kinase (FAK) signaling pathway and participates in the organization of focal adhesion complexes. Silencing of LOXL2 gene leads to reacquisition of epithelial cell polarity and decreases the migratory and invasive ability of mammary cell lines. The modulation of cell adhesion and cell polarity has been reported to be mediated by intracellular LOXL2. LOXL2 transcriptionally represses E- cadherin as well as tight junction and cell polarity genes by Snail 1 -dependent and Snail 1- independent mechanisms. LOXL2 has been more recently described to be associated with chromatin and reported to be involved in histone H3K4trimethyl deamination, a function that is dependent on the LOXL2 catalytic domain.

[0039] In some embodiments, the methods disclosed herein are methods for inhibiting intracellular LOXL2. In some embodiments, the methods disclosed herein are methods for inhibiting extracellular (secreted) LOXL2. In some embodiments, the methods disclosed herein are methods for inhibiting extracellular and intracellular LOXL2.

[0040] LOXL2 has been shown to be involved in fibrotic processes. Fibrotic processes include an excessive deposition of extracellular matrix components, such as collagen, which alters the physical, biochemical and biomechanical matrix properties leading to defective organ function and organ failure. Tissue fibrosis is also associated with cancer progression by direct promotion of cellular transformation, invasion, and metastasis. Tumors are typically stiffer than normal tissue and tumor rigidity influences tumor metastasis.

[0041] Excessive LOXL2 enzyme activity has been implicated in the increased stiffness of tumors. Elevated LOXL2 is also associated with fibrotic lesions from livers of patients suffering from Wilson disease and primary biliary cirrhosis. Additionally, the administration of a LOXL2- specific monoclonal antibody AB0023 was efficacious in reducing disease in a model of fibrosis. AB0023 was shown to inhibit the production of growth factors and of crosslinked collagenous matrix and TGF-beta signaling.

[0042] In some embodiments, disclosed herein is a method of controlling an abnormal accumulation or activation of cells, fibronectin, or collagen or increased fibroblast recruitment in a tissue of a mammal comprising administering a LOXL2 inhibitor described herein, or a pharmaceutically acceptable salt, or solvate thereof, to the mammal in need thereof.

[0043] In the context of tumors, treatment with AB0023 has been shown effective in reducing tumor volume, the extent of crosslinked collagen, and microvessel density. AB0023 also inhibited the activation of fibroblasts.

[0044] LOXL2 has been reported to be responsible for fibroblast activation and extracellular matrix remodeling in cancer and fibrosis models. Described herein is the attenuation of collagen deposition of rheumatoid arthritis synovial fibroblasts (RASFs) with LOXL2 inhibitors. In some embodiments, the LOXL2 inhibitors are used in the treatment of autoimmune diseases or inflammatory diseases or conditions.

[0045] The methods described herein include administering to a subject in need a composition containing a therapeutically effective amount of LOXL-2 inhibitor compound. In some embodiments, the methods described herein are used to treat an autoimmune disease or condition, or an inflammatory disease or condition in a mammal.

[0046] In some embodiments, the methods described herein are used to treat an autoimmune disease in a mammal. In some embodiments, the autoimmune disease is rheumatoid arthritis, psoriatic arthritis, osteoarthritis, Still's disease, juvenile arthritis, lupus, diabetes, myasthenia gravis, Hashimoto's thyroiditis, Ord's thyroiditis, Graves' disease Sjogren's syndrome, multiple sclerosis, Guillain-Barre syndrome, acute disseminated encephalomyelitis, Addison's disease, opsoclonus-myoclonus syndrome, ankylosing spondylitis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hepatitis, coeliac disease, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Reiter's syndrome, Takayasu's arteritis, temporal arteritis, warm autoimmune hemolytic anemia, Wegener's granulomatosis, psoriasis, alopecia universalis, Behcet's disease, chronic fatigue, dysautonomia, endometriosis, interstitial cystitis, neuromyotonia, scleroderma, or vulvodynia.

[0047] In further embodiments, the methods described herein are used to treat an inflammatory disease or condition in a mammal. In some embodiments the inflammatory disease or condition is asthma, inflammatory bowel disease, appendicitis, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, colitis, conjunctivitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, hepatitis, hidradenitis suppurativa, laryngitis, mastitis, meningitis, myelitis myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonitis, pneumonia, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, uveitis, vaginitis, vasculitis, or vulvitis. Autoimmune Diseases

Rheumatoid Arthritis

[0048] Rheumatoid arthritis (RA) is a chronic autoimmune disorder in which the body's immune system attacks the joints and additional organs such as skin, eyes, lungs, and blood vessels. Symptoms of RA manifest as inflammation in the joints (arthritis) and can quickly progress to involve painful swelling and deterioration of the surrounding tissues and organs. In some instances, symptoms of RA include pain, swollen and/or stiff joints, rheumatoid nodules, low red blood cells, and inflammation around the lungs and heart. Thus, RA can be very debilitating as patients may experience substantial loss of function and mobility in the hands, wrists, and feet.

[0049] Active rheumatoid arthritis (RA) originates from few joints but subsequently affects the majority of joints. RA is a chronic inflammatory disease characterized by synovial hyperplasia consisting of infiltrated immune cells and resident synovial fibroblasts (SF). Rheumatoid arthritis synovial fibroblasts (RASFs) are found in RA synovium and are key players in joint destruction and are able to migrate in vitro and in vivo. Various cytokines from infiltrated immune cells induce proliferation and activation of SF. Activated SF in turn generates pathogenic stroma to sustain chronic inflammation, leading to cartilage and bone destruction.

[0050] The transmigration of activated RASFs has been implicated in the spread of arthritis between joints. RASF are the most common cell type at sites of invasion. Implanting healthy human cartilage together with RASF into severe combined immunodeficient mice, it has been demonstrated that activated RASF migrate in vivo and spread the disease to sites of implanted cartilage. Whereas RASF actively degraded human cartilage, control implanted SF from osteoarthritis (OA) patients and dermal fibroblasts from healthy donors did not (Stephanie Lefevre, et al., Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nature Medicine 15, 1414 - 1420 (2009)). Since RASF were able to destroy cartilage even in the absence of cellular and humoral immune responses, RASF is capable of maintaining their activated phenotype without further stimulation of the inflammatory environment in the synovium.

[0051] RASF differ from healthy synovial fibroblasts by their morphology and an aberrant gene expression pattern. RASF are characterized by the expression of antiapoptotic molecules, protooncogenes and a lack of expression of tumor suppressor genes. Owing to their ability to produce pro-inflammatory cytokines and chemokines, RASF further attract inflammatory cells of the immune system to the synovium. In addition, RASF produce enzymes such as matrix metalloproteinases (MMPs) that promote invasion into and destruction of cartilage.

[0052] LOXL2 is expressed and secreted in RASF and is up-regulated by T F-a and IL-Ιβ. Knockdown of LOXL2 and antibodies against LOXL2 attenuated collagen deposition of RASF. Furthermore, LOXL2 knockdown reduced RASF proliferation and invasion. For example, the pan-LOX inhibitor β-aminopropionitrile (BAPN) ameliorated collagen induced arthritis (CIA) in an in vivo CIA mouse model (Tetsuya Saito, et al., Roles of collagen crosslinking enzyme, lysyl oxidase-like 2, in rheumatoid synovial fibroblasts, Keystone Symposia on Molecular and Cellular Biology, February 7-11, 2016, abstract Q3 3014).

[0053] LOXL2 is implicated in the activated phenotypes of RASF and represents a therapeutic target of RA. The aggressive, invasive phenotype of RASF appears early in RA as a

consequence of stable cell activation. Several key factors in the pathogenesis of RA, including proinflammatory cytokines, innate immunity and matrix-degradation products, critically amplify activation of RASF.

[0054] Current disease-modifying and anti-cytokine therapies, despite effectively halting or slowing inflammation and progression of RA, offer rather limited protection against ongoing joint destruction, with a substantial number of patients responding inadequately or not at all. Although these treatments can dampen the destructivity of RASF, reversing the activated phenotype of RASF remains unaccomplished. Arthritis typically flares up after discontinuing treatment and a cure for RA has not been found.

[0055] Though there is no known cure for RA, there are different types of treatments available to alleviate symptoms and modify the disease progression. Unfortunately, many of the available therapies have significant side effects and long-term risks. Current drugs for RA, which inhibit inflammatory cytokines or immune cells, achieve insufficient remission. Such therapies are not without side effects, such as serious infections due in part to the suppression of the immune system. Thus, drugs targeting RASF represent a useful therapy for RA. [0056] In some embodiments, agents suitable for treatment of RA include, but are not limited to, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate,

hydroxychloroquine, sulfasalazine, leflunomide, tofacitinib, abatacept, or anakinra; biologies such as tumor necrosis factor alpha blockers (e.g., infliximab, adalimumab, golimumab, etanercept), interleukin 1 blockers (e.g., anakinra), monoclonal antibodies (e.g., rituximab, tocilizumab), T cell costimulation blockers (e.g., abatacept); nonsteroidal anti-inflammatory drugs (NSAIDs); COX-2 inhibitors (e.g., celecoxib); or glucocorticoids.

[0057] In some embodiments, described herein is the use of LOXL2 inhibitors in the modulating RASF activity in a mammal. In some embodiments, the modulation of RASF activity in a mammal with a LOXL2 inhibitor is used to protect joint destruction in RA. In some embodiments, described herein is the use of LOXL2 inhibitors in the protection of joint destruction in RA.

[0058] In some embodiments, administration of LOXL2 inhibitors described herein to a mammal with RA attenuates the activation of RASF. In some embodiments, the administration of LOXL2 inhibitors described herein to a mammal with RA precludes the development of more chronic and aggressive disease.

[0059] In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of RA. In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of RA in combination with one or more additional agents used to treat RA.

[0060] In some instances, RA is classified into rheumatoid factor positive (seropositive) RA, rheumatoid factor negative (seronegative) RA, and juvenile RA (or juvenile idiopathic arthritis). Rheumatoid factor (RF) is an autoantibody directed against the Fc region of IgG. In some cases, rheumatoid factor comprises one or more isotype of immunoglobulin, such as for example, IgA, IgG, IgM, IgE, or IgD. Presence or absence of rheumatoid factor (i.e., seropositive or seronegative) is used as part of a diagnostic tool in evaluating the presence and progression of RA.

Juvenile Idiopathic Arthritis

[0061] Juvenile idiopathic arthritis (JIA), also known as juvenile rheumatoid arthritis (JRA), is the most common form of arthritis in children and adolescents. Juvenile in this context refers to an onset before age 16.

[0062] JIA is an autoimmune, non-infective, inflammatory joint disease. It is a subset of arthritis seen in childhood, which may be transient and self-limited or chronic. It differs significantly from arthritis commonly seen in adults (osteoarthritis, rheumatoid arthritis), and other types of arthritis that can present in childhood which are chronic conditions (e.g. psoriatic arthritis and ankylosing spondylitis). Aetiopathology is similar to rheumatoid arthritis but with less marked cartilage erosion, and joint instability and absent rheumatoid factor.

[0063] In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of JIA. In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of JIA in combination with one or more additional agents used to treat JIA.

Psoriasis

[0064] Psoriasis is an autoimmune disease characterized by regions of abnormal skin. In some instances, psoriasis is further classified into plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis or psoriasis vulgaris comprise about 90% of total cases. It is characterized by the presence of red patches with white scales on top. In some cases, plaque psoriasis occurs at the forearms, shins, navel, and the scalp region. Guttate psoriasis is characterized by drop shaped lesions. Pustular psoriasis is characterized by small non-infectious pus filled blisters. Inverse psoriasis is characterized by red patches in the skin fold regions. Erythrodermic psoriasis is characterized by rashes throughout the body and in some instances further develops into the subtypes of psoriasis. In some instances, psoriasis in combination with inflammation of the joints is termed psoriatic arthritis.

[0065] In some embodiments, treatments of psoriasis include nonsteroidal anti-inflammatory drugs (NSAIDs); immunosuppressant such as methotrexate; fumarates such as dimethyl fumarate; biologies such as infliximab, adalimumab, golimumab, and certolizumab pegol;

retinoids; vitamin D3 cream, or phototherapy such as ultraviolet light.

[0066] In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of psoriasis. In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of psoriasis in combination with one or more additional agents used to treat psoriasis. Psoriatic Arthritis

[0067] Psoriatic arthritis is a type of inflammatory arthritis that will develop in up to 30 percent of people who have psoriasis. Psoriatic arthritis is classified as a seronegative

spondyloarthropathy and therefore occurs more commonly in patients with tissue type HLA-B27.

[0068] There are several types of psoriatic arthritis. Asymmetric psoriatic arthritis affects around 70% of patients and is generally mild. This type does not occur in the same joints on both sides of the body and usually only involves fewer than 3 joints. Symmetric psoriatic arthritis accounts for around 25% of cases, and affects joints on both sides of the body simultaneously.

This type is most similar to rheumatoid arthritis and is disabling in around 50% of all cases.

Arthritis mutilans affects less than 5% of patients and is a severe, deforming and destructive arthritis. This condition can progress over months or years causing severe joint damage. Arthritis mutilans has also been called chronic absorptive arthritis, and may be seen in rheumatoid arthritis as well. Distal interphalangeal predominant psoriatic arthritis is found in about 5% of patients, and is characterised by inflammation and stiffness in the joints nearest to the ends of the fingers and toes. Nail changes are often marked.

[0069] In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of psoriatic arthritis. In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of psoriatic arthritis in combination with one or more additional agents used to treat psoriatic arthritis.

Osteoarthritis

[0070] Osteoarthritis (OA) is a type of joint disease that results from breakdown of joint cartilage and underlying bone. The most common symptoms are joint pain and stiffness. The most commonly involved joints are those near the ends of the fingers, at the base of the thumb, neck, lower back, knees, and hips. Joints on one side of the body are often more affected than those on the other. Usually the symptoms come on over years. It can affect work and normal daily activities. Unlike other types of arthritis, only the joints are typically affected.

[0071] LOXL2 has been shown to be highly expressed in the damaged region of OA cartilage (T. Sato et al., Arthritis & Rheumatism, Vol. 54, No. 3, pp 808-817 (2006)). In some

embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of osteoarthritis. In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of osteoarthritis in combination with one or more additional agents used to treat osteoarthritis. Ankylosing Spondylitis

[0072] Ankylosing spondylitis (also known as Bekhterev's disease, Marie-Striimpell disease, or AS) is a chronic inflammatory disease of the axial skeleton. Ankylosing spondylitis mainly affects the spinal joints and the sacroiliac joint of the pelvis, although in some instances peripheral joints and nonarticular structures are also involved. In some cases, ankylosing spondylitis is characterized by the ossification of the outer fibers of the fibrous ring of the intervertebral discs, and in severe cases with complete fusion of the spine. Symptoms of ankylosing spondylitis include pain and stiffness of lower back and hips, gradual loss of spinal mobility and chest expansion, limitation of anterior flexion, lateral flexion, and extension of the lumbar spine.

[0073] In some instances, treatments include nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, phenylbutazone, diclofenac, indomethacin, naproxen and COX-2 inhibitors; opioid analgesics; disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine; tumor necrosis factor-alpha blockers such as etanercept, infliximab, golimumab, and

adalimumab; and anti-interleukin-6 inhibitors such as tocilizumab and rituximab. [0074] In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of ankylosing spondylitis. In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of ankylosing spondylitis in combination with one or more additional agents used to treat ankylosing spondylitis.

Systemic sclerosis

[0075] Scleroderma, or systemic sclerosis, is a chronic connective tissue disease generally classified as one of the autoimmune rheumatic diseases. Scleroderma, also known as systemic sclerosis or SSc, is a connective tissue disease characterized by sclerosis or hardening of skin, blood vessels, and internal organs, and inflammation of joints and muscles.

[0076] Hardening of the skin is one of the most visible manifestations of the disease. There are two major classifications of scleroderma: localized scleroderma and systemic sclerosis (SSc).

[0077] In limited scleroderma, disease is limited to a few places on the skin or muscles, and rarely spread elsewhere. The internal organs are usually not affected, and persons with localized scleroderma rarely develop systemic scleroderma. Limited scleroderma affects the face, hands and feet, and is characterized by calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia.

[0078] The changes occurring in scleroderma (systemic sclerosis) may affect the connective tissue in many parts of the body. Scleroderma can involve the skin, esophagus, gastrointestinal tract (stomach and bowels), lungs, kidneys, heart and other internal organs. It can also affect blood vessels, muscles, and joints. The tissues of involved organs become hard and fibrous, causing them to function less efficiently. The term systemic sclerosis indicates that "sclerosis" (hardening) may occur in the internal systems of the body. There are two major recognized patterns that the illness can take - diffuse or limited disease. In diffuse scleroderma, skin thickening occurs more rapidly and involves more skin areas than in limited disease. In addition, people with diffuse scleroderma have a higher risk of developing "sclerosis" or fibrous hardening of the internal organs.

[0079] In some cases, treatments include calcium channel blockers, prostanoids, tadalafil, bosentan, corticosteroids, and immunosuppressants.

[0080] In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of systemic scleroderma. In some embodiments, described herein is the use of a LOXL2 inhibitor in the treatment of systemic scleroderma in combination with one or more additional agents used to treat systemic scleroderma.

[0081] In some embodiments, reducing activation of synovial fibroblasts includes reducing or inhibiting one or more of: formation or deposition of extracellular matrix proteins; the number of pro-fibrotic cell types (e.g., fibroblast or immune cell numbers); cellular collagen or hydroxyproline content within a fibrotic lesion; expression or activity of a fibrogenic protein; or reducing fibrosis associated with an inflammatory response.

[0082] In some embodiments, disclosed herein is a method of controlling an abnormal accumulation or activation of cells, fibronectin, or collagen or increased fibroblast recruitment in a tissue of a mammal comprising administering a LOXL2 inhibitor described herein, or a pharmaceutically acceptable salt, or solvate thereof, to the mammal in need thereof. In some embodiments, the abnormal accumulation or activation of cells, fibronectin, or collagen or increased fibroblast recruitment in the tissue results in arthritis.

[0083] In some embodiments, described herein is a method of controlling an abnormal accumulation or activation of cells, fibronectin, or collagen or increased fibroblast recruitment in tissues of a mammal comprising administering to mammal in need thereof a LOXL2 inhibitor described herein, or a pharmaceutically acceptable salt, or solvate thereof. In some

embodiments, the abnormal accumulation or activation of cells, fibronectin, or collagen or increased fibroblast recruitment in the synovial tissues results in inflammation.

Compounds

[0084] Compounds contemplated for use in the methods of treatment described herein are LOXL2 inhibitors, including pharmaceutically acceptable salts, prodrugs, active metabolites and pharmaceutically acceptable solvates thereof.

[0085] In some embodiments, lysyl oxidase like-2 (LOXL2) inhibitors described herein are used in the treatment or prevention of a disease or condition in a mammal that would benefit from the inhibition or reduction of lysyl oxidase like-2 (LOXL2) activity. In some embodiments, the disease or condition is an autoimmune disease or condition or an inflammatory disease or condition.

[0086] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted arylmethylamine compound or a substituted or unsubstituted heterocyclylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

[0087] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted arylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted phenylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted naphthylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof.

[0088] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted heterocyclyl compound, or a pharmaceutically acceptable salt, or solvate thereof. [0089] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted heteroarylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted (monocyclic heteroaryl)methyl amine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted (5-membered monocyclic heteroaryl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the 5-membered monocyclic heteroaryl is imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, oxadiazolyl, thiadiazolyl, or furazanyl. In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted (6-membered monocyclic heteroaryl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the 6-membered monocyclic heteroaryl is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl. In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted (bicyclic

heteroaryl)methyl amine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the bicyclic heteroaryl is indolizinyl, indolyl, benzofuranyl,

benzothiophenyl, indazolyl, benzimidazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, or pteridinyl.

[0090] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted (bicyclic heterocyclyl)methylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the bicyclic heterocyclyl is quinolinone, isoquinolinone, chromone, or coumarin. In some embodiments, the bicyclic heterocyclyl is quinolin-4-one, quinolin-2-one, chromone, or coumarin.

[0091] In some embodiments, the LOXL2 inhibitor is a substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the substituted pyridinylmethylamine compound is a substituted pyridin-4-ylmethylamine compound. In some embodiments, the substituted pyridinylmethylamine compound is a compound described in International patent application no. PCT/US2016/020731 titled "Lysysl Oxidase-Like 2 Inhibitors and Uses Thereof filed on March 3, 2016; which is herein incorporated by reference for such compounds.

[0092] In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted

pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (II), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (III), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (IV), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (V), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no.

PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (VI), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted

pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (VII), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (VIII), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (IX), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (X), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no.

PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (XI), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted

pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (XII), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731. In some embodiments, the substituted pyridinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof, has the structure of Formula (XIII), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020731.

[0093] In some embodiments, the LOXL-2 inhibitor is a compound described in Table 1, Table

2, Table 3, or Table 4, of International patent application no. PCT/US2016/020731.

[0094] In some embodiments, the LOXL-2 inhibitor is a substituted pyridinylmethylamine compound that is:

4-(4-(Aminomethyl)pyridin-2-yl)-/V-(2-methoxyethyl)benzamide ;

Racemic-(4-(4-(aminomethyl)pyridin-2-yl)phenyl)(3-hydroxy-3- (trifluorom ethyl )pyrrolidin-l- yl)methanone;

4-(4-(Aminomethyl)pyridin-2-yl)-/V-phenylbenzamide;

4-(4-(Aminomethyl)pyridin-2-yl)-/V-benzylbenzamide;

3-(4-(Aminomethyl)pyridin-2-yl)-/V-(2-methoxyethyl)benzam ide;

Racemic-(3-(4-(aminomethyl)pyridin-2-yl)phenyl)(3-hydroxy-3- (trifluorom ethyl )pyrrolidin-l- yl)methanone;

3-(4-(Aminomethyl)pyridin-2-yl)-/V-phenylbenzamide;

3-(4-(Aminomethyl)pyridin-2-yl)-/V-benzylbenzamide;

3-(4-(Aminomethyl)pyridin-2-yl)-/V-(5-chloro-2-methylphen yl)benzamide;

3- (4-(Aminomethyl)pyridin-2-yl)-/V-(6-chloro-lH-indol-4-yl)ben zamide;

4- ((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(2-methoxyethyl)benzam ide;

Racemic-4-((4-(aminomethyl)pyridin-2-yl)oxy)phenyl)(3-hydrox y-3-(trifluoromethyl)pyrrolidin- l-yl)methanone;

4-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-phenylbenzamide;

4-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-benzylbenzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(2-methoxyethyl)benz amide;

Racemic-(3 -((4-(aminom ethyl )pyridin-2-yl)oxy)phenyl)(3 -hydroxy-3 -

(trifluoromethyl)pyrrolidin- 1 -yl)methanone;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-phenylbenzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-benzylbenzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(3-methoxyphenyl)ben zamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(4-methoxyphenyl)ben zamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(3-(trifluoromethyl) phenyl)benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(4-(trifluoromethyl) phenyl)benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(4-fluorophenyl)benz amide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(2,4-difluorophenyl) benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-/V-(4-bromophenyl)benza mide; Methyl 4-(3-((4-(aminomethyl)pyridin-2-yl)oxy)benzamido)benzoate;

Ethyl 3-(3-((4-(aminomethyl)pyridin-2-yl)oxy)benzamido)benzoate;

3- (3-((4-(Aminomethyl)pyridin-2-yl)oxy)benzamido)benzoic acid;

4- (3-((4-(Aminomethyl)pyridin-2-yl)oxy)benzamido)benzoic acid;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(2,4-difluorobenzy l)benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(4-(trifluoromethy l)benzyl)benzamide;

3- ((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(4-bromobenzyl)benzamid e;

Methyl 4-((3-((4-(aminomethyl)pyridin-2-yl)oxy)benzamido)methyl)ben zoate ;

4- ((3-((4-(Aminomethyl)pyridin-2-yl)oxy)benzamido)methyl)benzo ic acid;

3-((3-((4-(Aminomethyl)pyridin-2-yl)oxy)benzamido)methyl) benzoic acid;

(R)-3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(2-hydroxy-l -phenyl ethyl)benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(3-fluoro-4-(lH-im idazol-l-yl)benzyl)benzamide ; 3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(4-(4-ethylpiperazin- l-yl)benzyl)benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(3-carbamimidoylbe nzyl)benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-phenethylbenzamide ;

(3-((4-(Aminomethyl)pyridin-2-yl)oxy)phenyl)(3,4-dihydroisoq uinolin-2(lH)-yl)methanone;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(benzo[^]thiophen- 2-ylmethyl)benzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-(pyrazin-2-ylmethyl)b enzamide;

3-((4-(Aminomethyl)pyridin-2-yl)oxy)-N-tridecylbenzamide;

3-(((4-(Aminomethyl)pyridin-2-yl)oxy)methyl)-N-phenylbenzami de;

or a pharmaceutically acceptable salt, or solvate thereof.

[0095] In some embodiments, the LOXL-2 inhibitor is a substituted pyridinylmethylamine compound that is:

Racemic-tra«5-(l -(4-(aminomethyl)pyridin-2-yl)-4-fluoropyrrolidin-3-ol;

Racemic-l-(4-(aminomethyl)pyridin-2-yl)-3-(trifluoromethy l)pyrrolidin-3-ol;

[2,3'-Bipyridin]-4-ylmethanamine;

(2-(4-Fluorophenyl)pyridin-4-yl)methanamine;

3- ((4-(Aminomethyl)pyridin-2-yl)oxy)benzoic acid;

4- (4-(Aminomethyl)pyridin-2-yl)benzoic acid;

(2-Phenoxypyridin-4-yl)methanamine;

(2-(3-Phenoxyphenoxy)pyridin-4-yl)methanamine;

4-((4-(Aminomethyl)pyridin-2-yl)oxy)benzoic acid;

(2-((l -Benzyl-lH-indol-4-yl)oxy)pyridin-4-yl)methanamine;

(2-((l -(2,4-Difluorobenzyl)-2 -methyl- lH-indol-4-yl)oxy)pyridin-4-yl)methanamine;

(2-((l -(2,4-Difluorobenzyl)-3 -methyl- lH-indol-4-yl)oxy)pyridin-4-yl)methanamine; (2-((l-((6-Methoxypyridin-3-yl)methyl)-2-m ethyl- lH-indol-4-yl)oxy)pyridin-4-yl)methanamine;

(2-((l-((6-Methoxypyridin-3-yl)methyl)-3-m ethyl- lH-indol-4-yl)oxy)pyridin-4-yl)methanamine;

(2-((l-((5-Fluoropyridin-2-yl)m ethyl)- lH-indol-4-yl)oxy)pyridin-4-yl) methanamine;

(2-((l-(Quinolin-2-ylmethyl)-lH-indol-4-yl)oxy)pyridin-4-yl) methanamine;

(2-((l-((2-(Trifluoromethyl)thiazol-5-yl)methyl)-lH-indol-4- yl)oxy)pyridin-4-yl)methanamine;

(2-((l-(4-Fluorophenyl)-lH-indol-4-yl)oxy)pyridin-4-yl)me thanamine;

(2-((l-(l-Methyl-lH-pyrazol-4-yl)-lH-indol-4-yl)oxy)pyridin- 4-yl)methanamine;

(2-((l-(6-Methoxypyridin-3-yl)-lH-indol-4-yl)oxy)pyridin-4-y l)methanamine;

(2-((l-(6-Fluorobenzo[<i]thiazol-2-yl)-lH-indol-4-yl)oxy) pyridin-4-yl)methanamine;

(2-((l-(4-Fluorophenethyl)-lH-indol-4-yl)oxy)pyridin-4-yl)me thanamine;

(2-((3-Bromo-l-(4-fluorophenethyl)-lH-indol-4-yl)oxy)pyridin -4-yl)methanamine;

(4-((4-(Aminomethyl)pyridin-2-yl)oxy)- lH-indol- 1 -yl)(phenyl)methanone;

4- ((4-(Aminomethyl)pyridin-2-yl)oxy)-N-phenyl-lH-indole-l-carb oxamide;

2-(4-((4-(Aminomethyl)pyridin-2-yl)oxy)-lH-indol-l-yl)-N, N-dimethylacetamide;

2-(4-((4-(Aminomethyl)pyridin-2-yl)oxy)-lH-indol-l-yl)-l -(piped din- l-yl)ethanone;

(R) or (5)-2-(4-((4-(Aminomethyl)pyridin-2-yl)oxy)-lH-indol-l-yl)-l -(3-hydroxy-3- (trifluoromethyl)piperidin-l-yl)ethan-l-one (Enantiomer 1);

(R) or (5)-2-(4-((4-(Aminomethyl)pyridin-2-yl)oxy)-lH-indol-l-yl)-l -(3-hydroxy-3- (trifluoromethyl)piperidin-l-yl)ethan-l-one (Enantiomer 2);

2-(4-((4-(Aminomethyl)pyridin-2-yl)oxy)-lH-indol-l-yl)-N-met hyl-N-phenylacetamide;

2-(4-((4-(Aminomethyl)pyridin-2-yl)oxy)- lH-indol- 1 -yl)- 1 -(3 ,4-dihydroquinolin- 1 (2H yl)ethanone;

(2-((lH-Indol-4-yl)oxy)pyridin-4-yl)methanamine;

(2-((l-(6-Fluorobenzo[<i]thiazol-2-yl)indolin-4-yl)oxy)py ridin-4-yl)methanamine;

(2-((l-((6-Methoxypyridin-3-yl)methyl)-lH-indol-5-yl)oxy) pyridin-4-yl)methanamine;

(2-((l -(2,4-Difluorobenzyl)-3 -methyl- lH-indazol-4-yl)oxy)pyridin-4-yl)methanamine;

5- ((4-(Aminomethyl)pyridin-2-yl)oxy)-l-(2,4-difluorobenzyl)-3, 4-dihydroquinolin-2(lH)-one; 5-((4-(Aminomethyl)pyridin-2-yl)oxy)-l-((6-methoxypyridin-3- yl)methyl)-3,4-dihydroquinolin- 2(lH)-one;

(,S)-(3-((4-(Aminomethyl)pyridin-2-yl)oxy)piperidin-l-yl)(ph enyl)methanone;

(S)-3-((4-(Aminomethyl)pyridin-2-yl)oxy)-iV-phenylpiperid ine-l-carboxamide;

Racemic-(4-(aminomethyl)pyridin-2-yl)(3 -hydroxy-3-(tri fluorom ethyl )pyrrolidin-l- yl)methanone;

4-(Aminomethyl)-N-benzylpicolinamide;

N-(4-(Aminomethyl)pyridin-2-yl)-2-fluoro-4-methylbenzamide; N-(4-(Aminomethyl)pyridin-2-yl)-2-(3,4-dichlorophenyl)acetam ide;

or a pharmaceutically acceptable salt, or solvate thereof.

[0096] In some embodiments, the LOXL-2 inhibitor is a substituted pyridinylmethylamine compound that is:

4-(Aminomethyl)-N,N-dimethyl-6-(3-phenoxyphenoxy)pyridin-2-a mine;

4-(Aminomethyl)-N-(2-methoxyethyl)-6-(3-phenoxyphenoxy)py ridin-2-amine;

(2-(4-Fluorophenyl)-6-(3-phenoxyphenoxy)pyridin-4-yl)meth anamine;

or a pharmaceutically acceptable salt, or solvate thereof

[0097] In some embodiments, the LOXL-2 inhibitor is a substituted pyridinylmethylamine compound that is:

2- Fluoro-3-(aminomethyl)pyridine;

3- Fluoro-4-(aminomethyl)pyridine;

2-Fluoro-4-(aminomethyl)pyridine;

2-Trifluoromethyl-4-(aminomethyl)pyridine;

2-Chloro-4-(aminomethyl)pyridine;

2-Benzyloxy-4-(aminomethyl)pyridine;

2-Cyclohexyloxy-4-(aminomethyl)pyridine;

2-(4-Fluorophenoxy)-4-(aminomethyl)pyridine;

2-(2-Trifluoromethylphenoxy)-4-(aminomethyl)pyridine;

2-(l-Pyrrolidino) -4-(aminomethyl)pyridine;

2-(Imidazol- 1 -yl)-4-(aminomethyl)pyridine;

2-(4-Ethylpiperazin- 1 -yl)-4-(aminomethyl)pyridine;

4- (Aminomethyl)-N-(2-methoxyethyl)picolinamide;

4-(Aminomethyl)-N-(2,2,2-trifluoroethyl)picolinamide;

or a pharmaceutically acceptable salt, or solvate thereof.

[0098] In some embodiments, the LOXL2 inhibitor is a substituted or unsubstituted 6-

(trifluoromethyl)pyridin-4-yl)methanamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the substituted 6-(trifluoromethyl)pyridin-4- yl)methanamine compound is a compound described in International patent application no.

PCT/US2016/020731 titled "Lysysl Oxidase-Like 2 Inhibitors and Uses Thereof filed on March

3, 2016; which is herein incorporated by reference for such compounds.

[0099] In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound described in International patent application no.

PCT/US2016/020732 titled "Fluorinated Lysyl Oxidase-Like 2 Inhibitors and Uses Thereof filed on March 3, 2016, which is herein incorporated by reference for such compound. [00100] In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (II), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (III), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (IV), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (V), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (VI), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (VII), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (VIII), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2016/020732.

[00101] In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (IX), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (X), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/020732. In some embodiments, the LOXL-2 inhibitor is a compound described in Table 1 of International patent application no. PCT/US2016/020732.

[00102] In some embodiments, the LOXL-2 inhibitor is a substituted or unsubstituted 6-

(trifluoromethyl)pyridin-4-yl)methanamine that is:

(6-(Trifluoromethyl)-[2,3'-bipyridin]-4-yl)methanamine; (2-([l, -Biphenyl]-3-yloxy)-6-(trifluoromethyl)pyridin-4-yl)methanam ine;

(2-(3-Phenoxyphenoxy)-6-(trifluoromethyl)pyridin-4-yl)methan amine;

(2-(3-(Phenoxymethyl)phenoxy)-6-(trifluoromethyl)pyridin-4-y l)methanamine;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-p henylaniline;

(2-(3-(lH-Pyrazol-4-yl)phenoxy)-6-(trifluoromethyl)pyridin-4 -yl)methanamine;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-p henylbenzamide;

3-((4-(Aminomethyl-i¾)-6-(trifluoromethyl)pyridin-2-yl)oxy) -N-phenylbenzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 4-fluorobenzyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- N-(benzo[^]thiophen-2- yl methyl )b enzami de ;

(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phe nyl)(3,4-dihydroisoquinoli 2( lH)-yl)methanone;

(3-(lH-Pyrazol-l-yl)azeti din- l-yl)(3-((4-(aminomethyl)-6-(trifluorom ethyl )pyridin-2- yl)oxy)phenyl)methanone;

N-((2H-Tetrazol-5-yl)methyl)-3-((4-(aminomethyl)-6-(trifluor omethyl)pyridin-2- yl )oxy)b enzami de ;

N-(2-(lH-l,2,4-Triazol-l-yl)ethyl)-3-((4-(aminomethyl)-6-(tr ifluoromethyl)pyridin-2- yl )oxy)b enzami de ;

N-(2-(lH-Tetrazol-l-yl)ethyl)-3-((4-(aminomethyl)-6-(trifluo romethyl)pyridin-2- yl )oxy)b enzami de ;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2-hydroxyethyl)benzamide; (<S)-(3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2-yl)oxy)phenyl)(3-hydroxypyrrolidin-l- yl)methanone;

(R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy )phenyl)(3-hydroxypyrrolidin-l- yl)methanone;

Racemic-tra«5-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyrid in-2-yl)oxy)phenyl)(3-fluoro-4- hydroxypyrrolidin-l-yl)methanone;

(<S , ,<S)-tra«5-(3-((4-(Aminomethyl)-6-(trifluoromethyl )pyridin-2-yl)oxy)phenyl)(3-fluoro-4- hydroxypyrrolidin-l-yl)methanone;

(R,R)-tra«5-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin -2-yl)oxy)phenyl)(3-fluoro-4- hydroxypyrrolidin-l-yl)methanone;

(R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy )phenyl)(3-aminopyrrolidin-l- yl)methanone;

Racemic-tra«5-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyrid in-2-yl)oxy)phenyl)(-3-

(dimethylamino)-4-hydroxypyrrolidin- 1 -yl)methanone; (<S)-l-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2- yl)oxy)benzoyl)pyrrolidine-2- carboxylic acid;

(R)-l-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)o xy)benzoyl)pyrrolidine-2- carboxylic acid;

(R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy )phenyl)(3- (hydroxymethyl)pyrrolidin- 1 -yl)methanone;

8-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)b enzoyl)-l-oxa-3,8- diazaspiro[4.5 ] decan-2-one;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2-(2-oxooxazolidin-3- yl )ethyl)b enzami de ;

Racemic-3-((4-(aminomethyl)-6-(trifluorom

yl )m ethyl )b enzami de ;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2- (methylsulfonyl)ethyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( l- (hy droxym ethyl )cycl opropyl)b enzami de ;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2-hydroxy-2- methylpropyl)b enzami de ;

(R)-3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy) -N-(2,3- dihydroxypropyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2-sulfamoylethyl)benzamide;

3- ((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2- (dimethylamino)ethyl)benzamide;

Racemic-tra«5-(3-(((4-(aminomethyl)-6-(trifluoromethyl)pyri din-2-yl)oxy)methyl)phenyl)(3- fluoro-4-hydroxypyrrolidin-l-yl)methanone;

(2-((l-(l-Methyl-lH-pyrazol-4-yl)-lH-indol-4-yl)oxy)-6-(trif luoromethyl)pyridin-4-yl) methanamine;

2-(4-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- lH-indol-l-yl)-N-methyl-N- phenylacetamide;

(R)-3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy) -N-phenylpyrrolidine-l- carboxamide;

(<S)-3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2-yl)oxy)-N-phenylpyrrolidine-l- carboxamide;

4- ((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-phe nylpiperidine-l-carboxamide; 4- (((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)methy l)-N-phenylpiperi carboxamide;

(R)-3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy) -N-phenylpiperidine-l- carboxamide;

(,S)-3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2-yl)oxy)-N-phenylpiperidine-l- carboxamide;

(,S)-3-(((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2-yl)oxy)methyl)-N-phenylpiperidine-l- carboxamide;

(,S)-l-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl) oxy)piperidin-l-yl)-2- phenylethanone;

(,S)-l-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl) oxy)piperidin-l-yl)-2-(3,4- di chl orophenyl)ethanone ;

(<S)-2-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2- yl)oxy)piperidine-l-carbonyl)-4H- chromen-4-one;

(,S)-(3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2-yl)oxy)piperi din- l-yl)(pyridin-3 - yl)methanone;

(,S)-(3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2-yl)oxy)piperi din- l-yl)(pyrimidin-5- yl)methanone;

(,S)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)ox y)piperidin-l-yl)(5-methyl-l,3,4- oxadiazol-2-yl)methanone;

(S)- 1 -(3 -((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)piper idin- 1 -yl)-2-methylpropan- 1-one;

5- ((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(2- (methylsulfonyl)ethyl)nicotinamide;

(R)-(5-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy )pyridin-3-yl)(3-aminopyrrolidi

1- yl)methanone;

Racemic-tra«5-(5-((4-(aminomethyl)-6-(trifluoromethyl)pyrid in-2-yl)oxy)pyridin-3-yl)(-3- fluoro-4-hydroxypyrrolidin-l-yl)methanone;

2- (4-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-lH -indol-l-yl)-l-(piperidin-l- yl)ethanone;

tert-Butyl 4-(2-(4-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)ox y)-lH-indol-l- yl)acetyl)piperazine-l-carboxylate;

(2-((lH-Indol-4-yl)oxy)-6-(trifluoromethyl)pyridin-4-yl)meth anamine;

5-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- 3,4-dihydroquinolin-2(lH)-one; 5-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-l-( 2-hydroxyethyl)-3,4- dihydroquinolin-2( lH)-one;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)thio)-N- phenylbenzamide;

3-(((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)amin o)methyl)-N-phenylbenza

3-(((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)amin o)methyl)-N-(2- (methylsulfonyl)ethyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)methyl)- l-benzyl-6-methylpyrim

2,4(lH,3H)-dione;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)methyl)- l-(2-hydroxyethyl)-6- methylpyrimidine-2,4(lH,3H)-dione;

4'-(Aminomethyl)-6'-(trifluoromethyl)-2H-[l,2'-bipyridin]-2- one;

l-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)ox y)phenyl)pyridin-2(lH)-one;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2-cyanoethyl)benzamide;

l-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)ox y)benzoyl)azetidine-3-carbonitrile;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- N-(oxetan-3-yl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( (l- hydroxycyclobutyl)methyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2-hydroxyethyl)-N- methylbenzamide;

(,S)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)ox y)phenyl)(3- (hydroxymethyl)piperidin-l-yl)methanone;

(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phe nyl)(4-(hydroxymethyl)pipe l-yl)methanone;

(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phe nyl)(4-hydroxy-4- methylpiperidin- 1 -yl)methanone;

(3-((4-(Aminomethyl)-6-(trifluoromethy^

1- yl)methanone;

(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phe nyl)(7-oxa-2-azaspiro[3.5]nonan-

2- yl)methanone;

3- ((4-(Aminomethyl)-6-(trifluoromethyl)^^

pyran-3-yl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( (lR,25)-2- hydroxycyclopentyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( (l ) S',2R)-2- hydroxycyclopentyl)benzamide; Racemic-c/5-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin- 2-yl)oxy)phenyl)(3-fluoro-4- hydroxypyrrolidin- 1 -yl)methanone;

(R)-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy )phenyl)(3-fluoropyrrolidin-l^ yl)methanone;

(,S)-(3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2-yl)oxy)phenyl)(3-fluoropyrrolidin-l- yl)methanone;

(3R,4R)-l-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2- yl)oxy)benzoyl)-4- fluoropyrrolidin-3-ylmethanesulfonate;

(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phe nyl)(2,5-dihydro-lH-pyrrol-l- yl)methanone;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( hex-5-yn-l-yl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 4-(l-phenyl-lH-l,2,3-triazol-4- yl)butyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-h ydroxybenzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- N-methoxybenzamide;

Methyl (,S)-3-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl) oxy)benzamido)pent-4- ynoate;

(,S)-3-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl) oxy)benzamido)pent-4-ynoic acid; Methyl (R)-3-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)o xy)benzamido)pent-4- ynoate;

(R)-3-(3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)o xy)benzamido)pent-4-ynoic acid;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)b enzoic acid;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 2-aminophenyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( pyrimidin-5-yl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( oxazol-2-yl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( l,3,4-oxadiazol-2-yl)benzamide;

Racemic-tra«5-(3-((4-(aminomethyl)-6-(trifluoromethyl)py ridin-2-yl)oxy)-4-hydroxyphenyl)(3- fluoro-4-hydroxypyrrolidin-l-yl)methanone;

Racemic-tra«5-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyrid in-2-yl)oxy)-5-hydroxyphenyl)(3- fluoro-4-hydroxypyrrolidin-l-yl)methanone;

Racemic-tra«5-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyrid in-2-yl)oxy)-4- (benzyloxy)phenyl)(3 -fluoro-4-hydroxypyrrolidin- 1 -yl)methanone;

Racemic-tra«5-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyrid in-2-yl)oxy)-5-methoxyphenyl)(3- fluoro-4-hydroxypyrrolidin-l-yl)methanone; 2-(4-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- lH-indol- 1 -yl)- 1 -(piperazin- 1 - yl)ethan-l-one;

2-(4-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- lH-indol-l-yl)-N- carb ami mi doyl acetami de ;

Ethyl 2-(5-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- 2-oxo-3,4-dihydroquinolin- l(2H)-yl)acetate;

2- (5-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-2- oxo-3,4-dihydroquinolin-l(2H)- yl)acetic acid;

(<S)-(3-(((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-y l)amino)methyl)phenyl)(3- hydroxypyrrolidin-l-yl)methanone;

Methyl 3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)carbamoy l)benzoate;

3- ((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)carbamoyl) benzoic acid;

N 1 -(4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)-N 3 -phenylisophthalamide;

(<S)-N-(4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-y l)-3-(3-hydroxypyrrolidine-l- carbonyl)benzamide;

N 1 -(4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)-N 3 -(2- (methylsulfonyl)ethyl)isophthal amide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)methyl)- 6-methyl-l-(pyrimidin-4- ylmethyl)pyrimidine-2,4(lH,3H)-dione;

l-(2-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)ox y)-6-azaspiro[3.4]octan-6- yl)ethanone;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( 3-ethylphenyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- N-(4-ethylphenyl)benzamide;

3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)- N-(3-ethynylphenyl)benzamide; 3-((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-( prop-2-yn-l-yl)benzamide;

3- ((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-(4- methyl-2-oxo-2H-chromen-7- yl)benzamide;

(R,S) or (,S',R)-c/5-(3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2 -yl)oxy)phenyl)(3 -fluoro-4- hydroxypyrrolidin-l-yl)methanone;

(R,S) or (,S',R)-c/5-(3-((4-(Aminomethyl)-6-(trifluorom ethyl )pyridin-2 -yl)oxy)phenyl)(3 -fluoro-4- hydroxypyrrolidin-l-yl)methanone;

4- ((4-(Aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)-N-phe nylpicolinamide;

or a pharmaceutically acceptable salt, or solvate thereof.

[00103] In some embodiments, the LOXL2 inhibitor for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the substituted or unsubstituted pyrimidinylmethylamine compound is a substituted or unsubstituted pyrimidin-4- ylmethylamine compound. In some embodiments, the substituted or unsubstituted

pyrimidinylmethylamine compound is a compound described in International patent application no. PCT/US2016/039253 titled "Lysyl Oxidase-Like 2 Inhibitors and Uses Thereof filed on

June 24, 2016, which is herein incorporated by reference for such compound.

[00104] In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (II), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no.

PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (III), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (Ilia), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no.

PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (IV), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (IVa), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no.

PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (V), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (Va), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no.

PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a substituted or unsubstituted pyrimidinylmethylamine compound of Formula (VI), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/039253. In some embodiments, the LOXL-2 inhibitor is a substituted or unsubstituted pyrimidinylmethylamine compound described in Table 1 of International patent application no. PCT/US2016/039253.

[00105] In some embodiments, the LOXL-2 inhibitor is a substituted or unsubstituted pyrimidinylmethylamine that is:

(6-(4-Fluorophenoxy)pyrimidin-4-yl)methanamine;

(6-(3-Phenoxyphenoxy)pyrimidin-4-yl)methanamine;

3- ((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-phenylbenzamide;

4- (3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)benzamido)benzoic acid;

4-((3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)benzamido)methy l)benzoic acid;

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(benzo[^]thiophe n-2-ylmethyl)benzamide;

3- (3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)benzamido)propanoic acid;

4- (3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)benzamido)butanoic acid;

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(2-hydroxyethyl) benzamide;

(<S)-(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(3- hydroxypyrrolidin-l-yl)methanone; Racemic-tra«5-(3-((6-(aminomethyl)pyrimidin-4-yl)oxy)phenyl )(3-fluoro-4-hydroxypyrrolidin-

1- yl)methanone;

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(2-(methylsulfonyl) ethyl)benzamide;

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(2-sulfamoylethy l)benzamide;

2- (5-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-2-oxo-3,4-dihydroqui nolin-l(2H)-yl)acetic acid; (5-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-l-(2-hydroxyethyl)-3 ,4-dihydroquinolin-2(lH)-one;

5- ((6-(Aminomethyl)pyrimidin-4-yl)oxy)-l-((6-methoxypyridin-3- yl)methyl)-3,4- dihydroquinolin-2( lH)-one;

(6-((lH-Indol-6-yl)oxy)pyrimidin-4-yl)methanamine;

(6-((lH-Indol-5-yl)oxy)pyrimidin-4-yl)methanamine;

(6-((lH-Indol-4-yl)oxy)pyrimidin-4-yl)methanamine;

(6-((l -Ethyl- lH-indol-4-yl)oxy)pyrimidin-4-yl)methanamine;

Methyl 2-(4-((6-(aminomethyl)pyrimidin-4-yl)oxy)-lH-indol-l-yl)acet ate;

2-(4-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-lH-indol-l-yl)acet ic acid;

2-(4-((6-(Aminomethyl)pyrimidin-4-yl)oxy)- lH-indol- 1 -yl)- 1 -(piperidin- 1 -yl)ethan- 1 -one;

2-(4-((6-(Aminomethyl)pyrimidin-4-yl)oxy)- lH-indol-l-yl)-N-m ethyl -N-phenylacetamide;

(6-((l-(2-(Methylsulfonyl)ethyl)-lH-indol-4-yl)oxy)pyrimi din-4-yl)methanamine;

(6-((l-Benzyl-lH-indol-4-yl)oxy)pyrimidin-4-yl)methanamine; Methyl 3 -((4-((6-(aminomethyl)pyrimidin-4-yl)oxy)- lH-indol- 1 -yl)methyl)benzoate;

3-((4-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-lH-indol-l-yl) methyl)benzoic acid;

(6-((l-((6-Methoxypyridin-3-yl)methyl)-lH-indol-5-yl)oxy) pyrimidin-4-yl)methanamine;

(6-((l-((6-Methoxypyridin-3-yl)methyl)-2-m ethyl- lH-indol-4-yl)oxy)pyrimidin-4- yl)methanamine;

(6-((l-((6-Methoxypyridin-3-yl)methyl)-3-m ethyl- lH-indol-4-yl)oxy)pyrimidin-4- yl)methanamine;

(6-((l-(l-Methyl-lH-pyrazol-4-yl)-lH-indol-4-yl)oxy)pyrimidi n-4-yl)methanamine;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N,N-dimethylb enzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(2-hydroxy- 2-methylpropyl)benzamide;

Racemic-(3-(((6-(aminomethyl)pyrimidin-4-yl)oxy)methyl)ph enyl)(3-hydroxy-3-

(trifluoromethyl)piperidin-l-yl)methanone;

Racemic-3-(((6-(aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-((3 -methyl-2-oxooxazolidin-5- yl)methyl)benzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(2-(methyls ulfonyl)ethyl)benzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(2-(2-oxoox azolidin-3-yl)ethyl)benzamide;

N-(2-(lH-Pyrazol-l-yl)ethyl)-3-(((6-(aminomethyl)pyrimidi n-4-yl)oxy)methyl)benzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-phenylbe nzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-benzylbenza mide;

3-((6-(Aminomethyl)pyrimidin-4-yl)amino)-N-phenylbenzamide;

3- (((6-(Aminomethyl)pyrimidin-4-yl)amino)methyl)-N-phenylbenza mide;

4- (3-(((6-(Aminomethyl)pyrimidin-4-yl)amino)methyl)benzamido)b enzoic acid;

3-(((6-(Aminomethyl)pyrimidin-4-yl)(methyl)amino)methyl)- N-phenylbenzamide;

N-(2-(lH-Tetrazol-l-yl)ethyl)-3-(((6-(aminomethyl)pyrimid in-4-yl)oxy)methyl)benzamide;

5- ((6-(Aminomethyl)pyrimidin-4-yl)oxy)-l-(2-(methylsulfonyl)et hyl)-3,4-dihydroquinolin- 2(lH)-one;

2- (4-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-lH-indol-l-yl)ethan- l-ol;

(6-((l-(Oxetan-3-yl)-lH-indol-4-yl)oxy)pyrimidin-4-yl)met hanamine;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(6-chloroin dolin-l-yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(2,3-dihydr o-lH-pyrrolo[2,3-^]pyridin-l- yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(2,3-dihydro-l H-pyrrolo[2,3-c]pyridin-l- yl)methanone;

N-((lH-Indol-2-yl)methyl)-3-((6-(aminomethyl)pyrimidin-4-yl) oxy)benzamide;

3- ((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(pyridin-3-ylmethyl)b enzamide; 3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-((2-chloropyridin-4 -yl)methyl)benzami 3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-benzylbenzamide;

(R)-3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(2-hydroxy-l -phenyl ethyl )benzamide;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(4-(pyridin-2- yl)piperazin-l-yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(4,4-dimeth ylpiperidin-l-yl)methanone);

(6-((lH-Indazol-4-yl)oxy)pyrimidin-4-yl)methanamine;

(l-(6-(Aminomethyl)pyrimidin-4-yl)-lH-indazol-4-yl)methanol;

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-((4'-fluoro-[l, -biphenyl]-4-yl)methyl)benzamide

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(quinolin-2-ylme thyl)benzamide;

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-((3-chlorobenzo[^]t hiophen-2-yl)methyl)benzamide;

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-((5-fluoro-lH-in dol-2-yl)methyl)benzamide;

3 -((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-((l -methyl- lH-indol-2-yl)m ethyl )benzamide;

N-((lH-Pyirolo[2,3-£]pyridin-2-yl)methyl)-3-((6-(am

3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-N-(benzo[<i]oxazol -2-ylmethyl)benzamide;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(5,6-dihydro-l ,7-naphthyridin-7(8H)- yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(3-methyl-6,7- dihydro-lH-pyrazolo[4,3- c]pyridin-5(4H)-yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(5H-pyrrolo[2, 3-b:5,4-c']dipyridin- 7(6H,8H,9H)-yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(4-phenylpiper azin-l-yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(4-(3,5-dichlo ropyridin-2-yl)piperazin-l- yl)methanone;

(3-((6-(Aminomethyl)pyrimidin-4-yl)oxy)phenyl)(4-hydroxy-4-( trifluoromethyl)piperidin-l- yl)methanone;

(^-Methyl 3-(3-((6-(aminomethyl)pyrimidin-4-yl)oxy)benzamido)pent-4-yn oate;

(R)-Methyl 3-(3-((6-(aminomethyl)pyrimidin-4-yl)oxy)benzamido)pent-4-yn oate;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(3-(trifluo romethyl)phenyl)benzami

(R)-3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(2-h ydroxy-l -phenyl ethyl )benzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(pyridin -3-ylmethyl)benzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-((2-chlorop yridin-4-yl)methyl)benzam

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(benzo[^ ]thiophen-2-ylmethyl)benzamid

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-((5-fluo robenzo[^]thiophen-2- yl )m ethyl )b enzami de ;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-(benzo[ii]o xazol-2-ylmethyl)benzami N-((lH-indol-2-yl)methyl)-3-(((6-(aminomethyl)pyrimidin-4-yl )oxy)methyl)benzami

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-((5-fluoro- lH-indol-2- yl )m ethyl )b enzami de ;

3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)-N-((l-methyl- lH-indol-2- yl )m ethyl )b enzami de ;

N-((lH-pyrrolo[2,3-^]pyridin-2-yl)methyl)-3-(((6-(aminomethy l)pyrimidin-4- yl)oxy)methyl)benzamide;

(3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)m ethyl )phenyl)(5,6-dihydro-l,7-naphthyridin-7(8H)- yl)methanone;

(3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)phenyl)(3-met hyl-6,7-dihydro-lH- pyrazolo[4,3-c]pyridin-5(4H)-yl)methanone;

(3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy )m ethyl )phenyl)(5H-pyrrolo[2,3-b:5,4-c']dipyridin- 7(6H,8H,9H)-yl)methanone;

(3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)phenyl)(4-phe nylpiperazin-l-yl)methanone; (3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)m ethyl )phenyl)(2,3-dihydro-lH-pyrrolo[2,3- b] pyridin- 1 -yl)methanone;

(3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)m ethyl )phenyl)(2,3-dihydro-lH-pyrrolo[2,3- c] pyridin- 1 -yl)methanone;

(3-(((6-(Aminomethyl)pyrimidin-4-yl)oxy)methyl)phenyl)(4-hyd roxy-4- (trifluoromethyl)piperidin-l-yl)methanone;

Racemic-3-(l-((6-(aminomethyl)pyrimidin-4-yl)oxy)ethyl)-N-ph enylbenzamide;

3-(((6-(Aminomethyl)pyrimidin-4-yl)amino)methy

3-(((6-(Aminomethyl)pyrimidin-4-yl)amino)methyl)-N-(benzo[^] thiophen-2- yl methyl )b enzami de ;

3- (((6-(Aminomethyl)pyrimidin-4-yl)amino)methyl)-N-((3-chlorob enzo[^]thiophen-2- yl)methyl)benzamide;

(l-(6-(Aminomethyl)pyrimidin-4-yl)-lH-indol-4-yl)methanol;

(3-(((6-(Aminomethyl)pyrimidin-4-yl)amino)methyl)phenyl)(4-p henylpiperazin-l-yl)methanone;

5-((6-(Aminomethyl)pyrimidin-4-yl)oxy)-3,4-dihydroquinoli n-2(lH)-one;

(R)-l-(6-(Aminomethyl)pyrimidin-4-yl)-N-phenylpyrrolidine-3- carboxamide;

l-(6-(Aminomethyl)pyrimidin-4-yl)-N-phenylpiperidine-4-ca rboxamide;

(4-(6-(Aminomethyl)pyrimidin-4-yl)piperazin-l-yl)(phenyl)met hanone;

4- (6-(Aminomethyl)pyrimidin-4-yl)-N-phenylpiperazine-l-carboxa mide;

1 -(4-(6-(Aminomethyl)pyrimidin-4-yl)piperazin- 1 -yl)-2-phenylethanone;

l-(6-(Aminomethyl)pyrimidin-4-yl)-5 -(benzyl oxy)-3,4-dihydroquinolin-2(lH)-one; or a pharmaceutically acceptable salt, or solvate thereof.

[00106] In some embodiments, the LOXL2 inhibitor for use in the methods of treatment described herein is a substituted or unsubstituted chromenonylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the substituted or unsubstituted chromenonylmethylamine compound is a substituted or unsubstituted chromen-4- onylmethylamine compound. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound described in International patent application no. PCT/US2016/042826 titled "Lysyl Oxidase-Like 2 Inhibitors and Uses Thereof filed on July 18, 2016, which is herein incorporated by reference for such compounds.

[00107] In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/042826. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (II), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/042826. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (III), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/042826. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (IV), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2016/042826. In some embodiments, the LOXL-2 inhibitor is a compound described in Table 1 of International patent application no.

PCT/US2016/042826.

[00108] In some embodiments, the LOXL-2 inhibitor is:

2-(aminomethyl)-6-bromo-4H-chromen-4-one;

2-(aminomethyl)-7-bromo-4H-chromen-4-one;

2-(aminomethyl)-6-ethynyl-4H-chromen-4-one;

2-(aminomethyl)-6-(3 -hy droxy-3 -methylbut- 1 -yn- 1 -yl)-4H-chromen-4-one;

2-(aminomethyl)-6-(3 -methylbut-3 -en- 1 -yn- 1 -yl)-4H-chromen-4-one;

2-(aminomethyl)-6-phenyl-4H-chromen-4-one;

2-(aminomethyl)-6-(pyridin-2-yl)-4H-chromen-4-one;

2-(aminomethyl)-6-(pyridin-3-yl)-4H-chromen-4-one;

2-(aminomethyl)-6-(quinolin-3-yl)-4H-chromen-4-one;

2-(aminomethyl)-6-(lH-pyrazol-l-yl)-4H-chromen-4-one;

2-(aminomethyl)-7-(lH-pyrazol-l-yl)-4H-chromen-4-one; 2-(aminomethyl)-6-(l -methyl- lH-pyrazol-4-yl)-4H-chromen-4-one;

2-(aminomethyl)-6-( 1 -methyl- IH- 1 ,2,3 -triazol-4-yl)-4H-chromen-4-one;

2-(aminomethyl)-6-( 1 -phenyl- IH- 1 ,2,3 -triazol-4-yl)-4H-chromen-4-one;

2-(aminomethyl)-6-( 1 -benzyl- IH- 1 ,2,3 -triazol-4-yl)-4H-chromen-4-one;

2-(aminomethyl)-6-(l-(2-hydroxy ethyl)- lH-1, 2,3 -triazol-4-yl)-4H-chromen-4-one;

2-(4-(2-(aminomethyl)-4-oxo-4H-chromen-6-yl)-lH-l,2,3-triazo l-l-yl)-N,N-dimethylacetamide;

2-(aminomethyl)-N,N-dimethyl-4-oxo-4H-chromene-6-carboxam ide;

2-(aminomethyl)-6-(piperidine-l-carbonyl)-4H-chromen-4-one;

(<S)-2-(aminomethyl)-6-(3-hydroxypyrrolidin-l-yl)-4H-chro men-4-one;

N-(2-(lH-l,2,4-triazol-l-yl)ethyl)-2-(aminomethyl)-4-oxo-4H- chromene-6-carboxamide;

2-(aminomethyl)-4-oxo-N-(2-sulfamoylethyl)-4H-chromene-6-car boxamide;

(R)-2-(aminomethyl)-6-(3-aminopyrrolidine-l-carbonyl)-4H-chr omen-4-one;

methyl (R)-l-(2-(aminomethyl)-4-oxo-4H-chromene-6-carbonyl)pyrrolid ine-3-carboxylate; racemic-trans-2-(aminomethyl)-6-(3-fluoro-4-hydroxypyrrolidi ne-l-carbonyl)-4H-chromen-4- one;

2-(aminomethyl)-N-(2-(methylsulfonyl)ethyl)-4-oxo-4H-chromen e-6-carboxamide;

2-(aminomethyl)-6-methoxy-4H-chromen-4-one;

2-(aminomethyl)-7-methoxy-4H-chromen-4-one;

2-(aminomethyl)-7-(benzyloxy)-4H-chromen-4-one;

2-(aminomethyl)-6-(benzyloxy)-4H-chromen-4-one;

2-(aminomethyl)-7-ethynyl-4H-chromen-4-one;

2-((2-(aminomethyl)-4-oxo-4H-chromen-7-yl)oxy)-N,N-dimethyla cetamide;

2-(aminomethyl)-7-( 1 -phenyl- IH- 1 ,2,3 -triazol-4-yl)-4H-chromen-4-one;

2-((2-(aminomethyl)-4-oxo-4H-chromen-6-yl)oxy)acetic acid;

2-((2-(aminomethyl)-4-oxo-4H-chromen-6-yl)oxy)-N,N-dimethyla cetamide;

methyl (,S)-l-(2-(aminomethyl)-4-oxo-4H-chromene-6-carbonyl)pyrroli dine-3-carboxylate;

(R) or (,S)-l-(2-(aminomethyl)-4-oxo-4H-chromene-6-carbonyl)pyrroli dine-3-carboxylic acid;

(R) or (,S)-l-(2-(aminomethyl)-4-oxo-4H-chromene-6-carbonyl)pyrroli dine-3-carboxylic acid;

2-(aminomethyl)-7-( 1 -methyl- IH- 1 ,2,3 -triazol-4-yl)-4H-chromen-4-one;

2-(aminomethyl)-7-(4-phenylpiperazin- 1 -yl)-4H-chromen-4-one;

2-(aminomethyl)-7-(4-benzoylpiperazin-l-yl)-4H-chromen-4-one ;

2-(aminomethyl)-7-(3,4-dihydroquinolin-l(2H)-yl)-4H-chromen- 4-one;

2-(aminomethyl)-7-hydroxy-4H-chromen-4-one;

2-(aminomethyl)-7-isobutoxy-4H-chromen-4-one;

2-(aminomethyl)-7-(prop-2-yn-l-yloxy)-4H-chromen-4-one; 2-(aminomethyl)-7-(2-phenoxyethoxy)-4H-chromen-4-one;

2- (aminomethyl)-7-((l-phenyl-lH-l,2,3-triazol-4-yl)methoxy)-4H -chromen-4-one;

3- (((2-(aminomethyl)-4-oxo-4H-chromen-7-yl)oxy)methyl)-N-pheny lbenzamide;

3-((2-(aminomethyl)-4-oxo-4H-chromen-7-yl)amino)-N-phenyl benzamide;

2-(aminomethyl)-8-bromo-4H-chromen-4-one;

2-(aminomethyl)-8-ethynyl-4H-chromen-4-one;

2-(aminomethyl)-8-hydroxy-4H-chromen-4-one;

2-(aminomethyl)-8-(prop-2-yn-l-yloxy)-4H-chromen-4-one;

2-(aminomethyl)-8-(benzyloxy)-4H-chromen-4-one;

2-(aminomethyl)-8-phenethoxy-4H-chromen-4-one;

2-(aminomethyl)-8-(2-phenoxyethoxy)-4H-chromen-4-one;

2- ((2-(aminomethyl)-4-oxo-4H-chromen-8-yl)oxy)-N-phenylacetami de;

3- (((2-(aminomethyl)-4-oxo-4H-chromen-8-yl)oxy)methyl)-N-pheny lbenzamide;

2-(aminomethyl)-N-(2-hydroxyethyl)-4-oxo-4H-chromene-6-ca rboxamide;

2-(aminomethyl)-6-((3,S',4 ) S)-3-fluoro-4-hydroxypyrrolidine-l-carbonyl)-4H-chrome n-4-one; 2-(aminomethyl)-6-((3R,4R)-3-fluoro-4-hydroxypyrrolidine-l-c arbonyl)-4H-chromen-4-one; 2-(aminomethyl)-7-((4-(trifluoromethyl)benzyl)oxy)-4H-chrome n-4-one;

2-(aminomethyl)-7-((3-phenylprop-2-yn-l-yl)oxy)-4H-chrome n-4-one;

2-(aminomethyl)-7-((4-methoxybenzyl)oxy)-4H-chromen-4-one ;

2-(aminomethyl)-7-(quinolin-2-ylmethoxy)-4H-chromen-4-one ;

2-(aminomethyl)-7-(benzo[^]thiophen-2-ylmethoxy)-4H-chrom en-4-one;

2-(aminomethyl)-7-(3-(trifluoromethyl)phenoxy)-4H-chromen -4-one;

2-(aminomethyl)-7-phenoxy-4H-chromen-4-one;

2-(aminomethyl)-7-(benzyloxy)-6-methoxy-4H-chromen-4-one;

2-(aminomethyl)-7-((l-phenyl-lH-pyrazol-4-yl)amino)-4H-ch romen-4-one;

or a pharmaceutically acceptable salt, or solvate thereof.

[00109] In some embodiments, the LOXL2 inhibitor for use in the methods of treatment described herein is a substituted or unsubstituted quinolinonylmethylamine compound, or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the substituted or unsubstituted quinolinonylmethylamine compound is a substituted or unsubstituted quinolin-4- onylmethylamine compound.

[00110] In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound described in International patent application no.

PCT/US2017/016847 titled "Quinolinone Lysyl Oxidase-Like 2 Inhibitors and Uses Thereof filed on February 7, 2017, which is herein incorporated by reference for such compounds. [00111] In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (II), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (III), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (IV), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (V), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (Va), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (Vb), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (VI), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (Via), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (VIb), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (VII), or a pharmaceutically acceptable salt, or solvate thereof, as described in

International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of

Formula (Vila), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor compound for use in the methods of treatment described herein is a compound of Formula (Vllb), or a pharmaceutically acceptable salt, or solvate thereof, as described in International patent application no. PCT/US2017/016847. In some embodiments, the LOXL-2 inhibitor is a compound described in Table 1 of International patent application no.

PCT/US2017/016847.

[00112] In some embodiments, the LOXL-2 inhibitor is:

2- (Aminomethyf quinolin-4( lH)-one;

2- (Aminomethyf -1- methylquinolin-4(lH)-one;

2- (Aminomethyf -6- bromoquinolin-4( lH)-one;

2- (Aminomethyf -6- ethynylquinolin-4(lH)-one;

2- (Aminomethyf -6- phenyl quinolin-4( lH)-one;

2- (Aminomethyf -6- (1 -phenyl- IH- 1 ,2,3 -triazol-4-yl)quinolin-4( lH)-one

2- (Aminomethyf -6- (phenylethynyl)quinolin-4(lH)-one;

2- (AminomethyF -6- (lH-pyrazol-l-yl)quinolin-4(lH)-one;

2- (Aminomethyf -6- methoxyquinolin-4( lH)-one;

2- (AminomethyF -6- hydroxy quinolin-4( lH)-one;

2- (AminomethyF -6- (4-fluorophenyl)quinolin-4(lH)-one;

2- (AminomethyF -6- (3-fluorophenyl)quinolin-4(lH)-one;

2- (AminomethyF -6- (2-fluorophenyl)quinolin-4(lH)-one;

2- (AminomethyF -6- (1H- 1 ,2,3 -triazol- 1 -yl)quinolin-4( lH)-one;

2- (AminomethyF -6- (2H-tetrazol-2-yl)quinolin-4(lH)-one;

2- (AminomethyF -6- (lH-tetrazol-l-yl)quinolin-4(lH)-one;

2- (AminomethyF -6- (2 -methyl -2H-tetrazol-5-yl)quinolin-4(lH)-one;

2- (AminomethyF -6- ((4-fluorophenyl)ethynyl)quinolin-4(lH)-one;

2- (AminomethyF -6- ((3 -fluorophenyl)ethynyl)quinolin-4( lH)-one;

2- (AminomethyF -6- ((2-fluorophenyl)ethynyl)quinolin-4(lH)-one;

2- (AminomethyF -6- phenoxyquinolin-4( lH)-one;

2- (AminomethyF -6- (2-fluorophenoxy)quinolin-4(lH)-one;

2- (AminomethyF -6- (3 -fluorophenoxy)quinolin-4( lH)-one;

2- (AminomethyF -6- (4-fluorophenoxy)quinolin-4(lH)-one;

2- (AminomethyF -6- (benzyloxy)quinolin-4(lH)-one;

2- (AminomethyF -6- ((2-fluorobenzyl)oxy)quinolin-4(lH)-one;

2- (AminomethyF -6- ((3-fluorobenzyl)oxy)quinolin-4(lH)-one;

2- (AminomethyF -6- ((4-fluorobenzyl)oxy)quinolin-4(lH)-one; -(Aminomethyl)-6-(phenylamino)quinolin-4(lH)-one;

-(Aminomethyl)-6-(benzylamino)quinolin-4(lH)-one;

-(Aminomethyl)-6-(prop-2-yn-l-yloxy)quinolin-4(lH)-one;

-(Aminomethyl)-6-((4,4,44rifluorobut-2-yn-l-yl)oxy)quinol in-4(lH)-one;

-(Aminomethyl)-6-((3 -phenylprop-2-yn- 1 -yl)oxy)quinolin-4( lH)-one;

-(Aminomethyl)-6-(prop-2-yn-l-ylamino)quinolin-4(lH)-one;

-(Aminomethyl)-6-((4,4,44rifluorobut-2-yn-l-yl)amino)quin olin-4(lH)-one;

-(Aminomethyl)-6-((3 -phenylprop-2-yn- 1 -yl)amino)quinolin-4( lH)-one;

-(Aminomethyl)-6-(pyridin-2-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(pyridin-3-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(pyridin-4-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(pyrimidin-5-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(pyrazin-2-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(oxazol-2-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(thiazol-2-yl)quinolin-4(lH)-one;

'-(Aminomethyl)-[2,6'-biquinolin]-4'(rH)-one;

'-(Aminomethyl)-[3,6'-biquinolin]-4'(rH)-one;

-(Aminomethyl)-6-(5 -m ethyl -2-oxopyri din- l(2H)-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(l-methyl-lH-pyrazol-4-yl)quinolin-4(lH) -one;

-(Aminomethyl)-6-(l -phenyl- lH-pyrazol-4-yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-(4-phenyl- lH-pyrazol- 1 -yl)quinolin-4(lH)-one;

-(Aminomethyl)-6-((l-methyl-lH-pyrazol-4-yl)amino)quinoli n-4(lH)-one;

-(Aminomethyl)-6-((l-phenyl-lH-pyrazol-4-yl)amino)quinoli n-4(lH)-one;

-(Aminomethyl)-6-((l -(2 -fluorophenyl)- lH-pyrazol-4-yl)amino)quinolin-4(lH)-one;

-(Aminomethyl)-6-((l-(3-fluorophenyl)-lH-pyrazol-4-yl)ami no)quinolin-4(lH)-one;

-(Aminomethyl)-6-((l-(4-fluorophenyl)-lH-pyrazol-4-yl)ami no)quinolin-4(lH)-one;

'-(Aminomethyl)-3,4-dihydro-2H-[l,6'-biquinolin]-4'(rH)-o ne;

-(Aminomethyl)-6-(4-phenylpiperazin-l-yl)quinolin-4(lH)-o ne;

-(Aminomethyl)-6-(pyrrolidine-l-carbonyl)quinolin-4(lH)-o ne;

-(Aminomethyl)-6-((3,S',4 ) S)-3-fluoro-4-hydroxypyrrolidine-l-carbonyl)quinolin-4 (lH)-one;-(Aminomethyl)-6-((3R,4R)-3-fluoro-4-hydroxypyrroli dine-l-carbonyl)quinolin-4(lH)-one;-(Aminomethyl)-4-oxo- 1 ,4-dihydroquinoline-6-carboxamide;

-(Aminomethyl)-N-methyl-4-oxo-l,4-dihydroquinoline-6-carb oxamide;

-(Aminomethyl)-4-oxo- 1 ,4-dihydroquinoline-6-carboxylic acid;

-(Aminomethyl)-6-isopropoxyquinolin-4(lH)-one; 2-(Aminomethyl)-6-isobutoxyquinolin-4(lH)-one;

2-(Aminomethyl)-[6,8'-biquinolin]-4(lH)-one;

2-(Aminomethyl)-6-(5-(benzyloxy)pyridin-3-yl)quinolin-4(lH)- one;

2-(Aminomethyl)-6-(4-chlorophenyl)quinolin-4(lH)-one;

2-(Aminomethyl)-6-(3-chlorophenyl)quinolin-4(lH)-one;

2-(Aminomethyl)-6-(2-chlorophenyl)quinolin-4(lH)-one;

2-(Aminomethyl)-6-(2-chloro-4-fluorophenyl)quinolin-4(lH)-on e;

2-(Aminomethyl)-6-(4-chloro-2-fluorophenyl)quinolin-4(lH)-on e;

2-(Aminomethyl)-6-(3-fluoro-4-methoxyphenyl)quinolin-4(lH)-o ne;

2-(Aminomethyl)-6-(2-fluoro-4-methoxyphenyl)quinolin-4(lH)-o ne;

2-(Aminomethyl)-6-(6-(trifluoromethyl)pyridin-3-yl)quinolin- 4(lH)-one;

2-(Aminomethyl)-6-(5-(trifluoromethyl)pyridin-3-yl)quinolin- 4(lH)-one;

2-(Aminomethyl)-6-(4-(trifluoromethyl)pyridin-3-yl)quinolin- 4(lH)-one;

2-(Aminomethyl)-6-(2-(trifluoromethyl)pyrimidin-5-yl)quinoli n-4(lH)-one;

2-(Aminomethyl)-6-(2-methoxyethoxy)quinolin-4(lH)-one;

or a pharmaceutically acceptable salt, or solvate thereof.

[00113] In one aspect, compounds described herein are in the form of pharmaceutically acceptable salts. As well, active metabolites of these compounds having the same type of activity are included in the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[00114] "Pharmaceutically acceptable," as used herein, refers a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively nontoxic, i.e., the material is administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained.

[00115] The term "pharmaceutically acceptable salt" refers to a form of a therapeutically active agent that consists of a cationic form of the therapeutically active agent in combination with a suitable anion, or in alternative embodiments, an anionic form of the therapeutically active agent in combination with a suitable cation. Handbook of Pharmaceutical Salts: Properties, Selection and Use. International Union of Pure and Applied Chemistry, Wiley-VCH 2002. S.M. Berge,

L.D. Bighley, D.C. Monkhouse, J. Pharm. Sci. 1977, 66, 1-19. P. H. Stahl and C. G. Wermuth, editors, Handbook of Pharmaceutical Salts: Properties, Selection and Use,

Weinheim/Zurich:Wiley-VCH/VHCA, 2002. Pharmaceutical salts typically are more soluble and more rapidly soluble in stomach and intestinal juices than non-ionic species and so are useful in solid dosage forms. Furthermore, because their solubility often is a function of pH, selective dissolution in one or another part of the digestive tract is possible and this capability can be manipulated as one aspect of delayed and sustained release behaviours. Also, because the salt- forming molecule can be in equilibrium with a neutral form, passage through biological membranes can be adjusted.

[00116] In some embodiments, pharmaceutically acceptable salts are obtained by reacting a compound described herein with an acid. In some embodiments, the compound described herein (i.e. free base form) is basic and is reacted with an organic acid or an inorganic acid. Inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, and metaphosphoric acid. Organic acids include, but are not limited to, l-hydroxy-2-naphthoic acid; 2,2-dichloroacetic acid; 2-hydroxyethanesulfonic acid; 2- oxoglutaric acid; 4-acetamidobenzoic acid; 4-aminosalicylic acid; acetic acid; adipic acid;

ascorbic acid (L); aspartic acid (L); benzenesulfonic acid; benzoic acid; camphoric acid (+); camphor- 10-sulfonic acid (+); capric acid (decanoic acid); caproic acid (hexanoic acid); caprylic acid (octanoic acid); carbonic acid; cinnamic acid; citric acid; cyclamic acid; dodecylsulfuric acid; ethane- 1,2-disulfonic acid; ethanesulfonic acid; formic acid; fumaric acid; galactaric acid; gentisic acid; glucoheptonic acid (D); gluconic acid (D); glucuronic acid (D); glutamic acid; glutaric acid; glycerophosphoric acid; glycolic acid; hippuric acid; isobutyric acid; lactic acid (DL); lactobionic acid; lauric acid; maleic acid; malic acid (- L); malonic acid; mandelic acid (DL); methanesulfonic acid; monomethyl fumarate, naphthalene- 1,5-disulfonic acid;

naphthalene-2-sulfonic acid; nicotinic acid; oleic acid; oxalic acid; palmitic acid; pamoic acid; phosphoric acid; proprionic acid; pyroglutamic acid (- L); salicylic acid; sebacic acid; stearic acid; succinic acid; sulfuric acid; tartaric acid (+ L); thiocyanic acid; toluenesulfonic acid (p); and undecylenic acid.

[00117] In some embodiments, a compound described herein is prepared as a chloride salt, sulfate salt, bromide salt, mesylate salt, maleate salt, citrate salt or phosphate salt. In some embodiments, a compound described herein is prepared as a hydrochloride salt.

[00118] In some embodiments, pharmaceutically acceptable salts are obtained by reacting a compound described herein with a base. In some embodiments, the compound described herein is acidic and is reacted with a base. In such situations, an acidic proton of the compound described herein is replaced by a metal ion, e.g., lithium, sodium, potassium, magnesium, calcium, or an aluminum ion. In some cases, compounds described herein coordinate with an organic base, such as, but not limited to, ethanolamine, diethanolamine, triethanolamine, tromethamine, meglumine, N-methylglucamine, dicyclohexylamine, tris(hydroxymethyl)methylamine. In other cases, compounds described herein form salts with amino acids such as, but not limited to, arginine, lysine, and the like. Acceptable inorganic bases used to form salts with compounds that include an acidic proton, include, but are not limited to, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydroxide, lithium hydroxide, and the like. In some embodiments, the compounds provided herein are prepared as a sodium salt, calcium salt, potassium salt, magnesium salt, meglumine salt, N-methylglucamine salt or ammonium salt. In some embodiments, the compounds provided herein are prepared as a sodium salt.

[00119] It should be understood that a reference to a pharmaceutically acceptable salt includes the solvent addition forms. In some embodiments, solvates contain either stoichiometric or non- stoichiometric amounts of a solvent, and are formed during the process of crystallization with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of compounds described herein are conveniently prepared or formed during the processes described herein. In addition, the compounds provided herein optionally exist in unsolvated as well as solvated forms.

[00120] The methods and formulations described herein include the use of N-oxides (if appropriate), crystalline forms (also known as polymorphs), or pharmaceutically acceptable salts of compounds described herein, as well as active metabolites of these compounds having the same type of activity.

[00121] In some embodiments, sites on the organic radicals (e.g. alkyl groups, aromatic rings) of compounds described herein are susceptible to various metabolic reactions. Incorporation of appropriate substituents on the organic radicals will reduce, minimize or eliminate this metabolic pathway. In specific embodiments, the appropriate substituent to decrease or eliminate the susceptibility of the aromatic ring to metabolic reactions is, by way of example only, a halogen, deuterium, an alkyl group, a haloalkyl group, or a deuteroalkyl group.

[00122] In another embodiment, the compounds described herein are labeled isotopically (e.g. with a radioisotope) or by another other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels.

[00123] Compounds described herein include isotopically-labeled compounds, which are identical to those recited in the various formulae and structures presented herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into the present compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine and chlorine, such as, for example, 2 H, 3 H, 13 C, 14 C, 15 N, 18 0, 17 0, 35 S, 18 F, and 36 C1. In one aspect, isotopically-labeled compounds described herein, for example those into which radioactive isotopes such as 3 H and 14 C are incorporated, are useful in drug and/or substrate tissue distribution assays. In one aspect, substitution with isotopes such as deuterium affords certain therapeutic advantages resulting from greater metabolic stability, such as, for example, increased in vivo half-life or reduced dosage requirements.

[00124] In some embodiments, the compounds described herein possess one or more stereocenters and each stereocenter exists independently in either the R or S configuration. The compounds presented herein include all diastereomeric, enantiomeric, atropisomers, and epimeric forms as well as the appropriate mixtures thereof. The compounds and methods provided herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the appropriate mixtures thereof.

[00125] Individual stereoisomers are obtained, if desired, by methods such as, stereoselective synthesis and/or the separation of stereoisomers by chiral chromatographic columns. In certain embodiments, compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds/salts, separating the diastereomers and recovering the optically pure enantiomers. In some embodiments, resolution of enantiomers is carried out using covalent diastereomeric derivatives of the compounds described herein. In another embodiment, diastereomers are separated by separation/resolution techniques based upon differences in solubility. In other embodiments, separation of stereoisomers is performed by chromatography or by the forming diastereomeric salts and separation by recrystallization, or chromatography, or any combination thereof. Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers,

Racemates and Resolutions", John Wiley and Sons, Inc., 1981. In some embodiments, stereoisomers are obtained by stereoselective synthesis.

[00126] In some embodiments, compounds described herein are prepared as prodrugs. A

"prodrug" refers to an agent that is converted into the parent drug in vivo. Prodrugs are often useful because, in some situations, they are easier to administer than the parent drug. They are, for instance, bioavailable by oral administration whereas the parent is not. The prodrug may be a substrate for a transporter. Further or alternatively, the prodrug also has improved solubility in pharmaceutical compositions over the parent drug. In some embodiments, the design of a prodrug increases the effective water solubility. An example, without limitation, of a prodrug is a compound described herein, which is administered as an ester (the "prodrug") but then is metabolically hydrolyzed to provide the active entity. A further example of a prodrug is a short peptide (polyaminoacid) bonded to an acid group where the peptide is metabolized to reveal the active moiety. In certain embodiments, upon in vivo administration, a prodrug is chemically converted to the biologically, pharmaceutically or therapeutically active form of the compound. In certain embodiments, a prodrug is enzymatically metabolized by one or more steps or processes to the biologically, pharmaceutically or therapeutically active form of the compound.

[00127] Prodrugs of the compounds described herein include, but are not limited to, esters, ethers, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl derivatives, quaternary derivatives of tertiary amines, N-Mannich bases, Schiff bases, amino acid conjugates, phosphate esters, and sulfonate esters. See for example Design of Prodrugs, Bundgaard, A. Ed., Elseview, 1985 and Method in Enzymology, Widder, K. et al, Ed.; Academic, 1985, vol. 42, p. 309-396; Bundgaard, H. "Design and Application of Prodrugs" in A Textbook of Drug Design and Development, Krosgaard-Larsen and H. Bundgaard, Ed., 1991, Chapter 5, p. 113-191; and Bundgaard, H., Advanced Drug Delivery Review, 1992, 8, 1-38, each of which is incorporated herein by reference. In some embodiments, a hydroxyl group in the compounds disclosed herein is used to form a prodrug, wherein the hydroxyl group is incorporated into an acyloxyalkyl ester, alkoxycarbonyloxyalkyl ester, alkyl ester, aryl ester, phosphate ester, sugar ester, ether, and the like. In some embodiments, a hydroxyl group in the compounds disclosed herein is a prodrug wherein the hydroxyl is then metabolized in vivo to provide a carboxylic acid group. In some embodiments, a carboxyl group is used to provide an ester or amide (i.e. the prodrug), which is then metabolized in vivo to provide a carboxylic acid group. In some embodiments, compounds described herein are prepared as alkyl ester prodrugs.

[00128] Prodrug forms of the herein described compounds, wherein the prodrug is metabolized in vivo to produce a compound described herein as set forth herein are included within the scope of the claims. In some cases, some of the herein-described compounds are prodrugs for another derivative or active compound.

[00129] In additional or further embodiments, the compounds described herein are metabolized upon administration to an organism in need to produce a metabolite that is then used to produce a desired effect, including a desired therapeutic effect.

[00130] A "metabolite" of a compound disclosed herein is a derivative of that compound that is formed when the compound is metabolized. The term "active metabolite" refers to a biologically active derivative of a compound that is formed when the compound is metabolized. The term

"metabolized," as used herein, refers to the sum of the processes (including, but not limited to, hydrolysis reactions and reactions catalyzed by enzymes) by which a particular substance is changed by an organism. Thus, enzymes may produce specific structural alterations to a compound. For example, cytochrome P450 catalyzes a variety of oxidative and reductive reactions while uridine diphosphate glucuronyltransferases catalyze the transfer of an activated glucuronic-acid molecule to aromatic alcohols, aliphatic alcohols, carboxylic acids, amines and free sulphydryl groups. Metabolites of the compounds disclosed herein are optionally identified either by administration of compounds to a host and analysis of tissue samples from the host, or by incubation of compounds with hepatic cells in vitro and analysis of the resulting compounds.

Certain Terminology

[00131] Unless otherwise stated, the following terms used in this application have the definitions given below. The use of the term "including" as well as other forms, such as

"include", "includes," and "included," is not limiting. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[00132] The term "acceptable" with respect to a formulation, composition or ingredient, as used herein, means having no persistent detrimental effect on the general health of the subject being treated.

[00133] The term "modulate" as used herein, means to interact with a target either directly or indirectly so as to alter the activity of the target, including, by way of example only, to enhance the activity of the target, to inhibit the activity of the target, to limit the activity of the target, or to extend the activity of the target.

[00134] The term "modulator" as used herein, refers to a molecule that interacts with a target either directly or indirectly. The interactions include, but are not limited to, the interactions of an agonist, partial agonist, an inverse agonist, antagonist, degrader, or combinations thereof. In some embodiments, a modulator is an antagonist. In some embodiments, a modulator is a degrader.

[00135] The terms "administer," "administering", "administration," and the like, as used herein, refer to the methods that may be used to enable delivery of compounds or compositions to the desired site of biological action. These methods include, but are not limited to oral routes, intraduodenal routes, parenteral injection (including intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular or infusion), topical and rectal administration. Those of skill in the art are familiar with administration techniques that can be employed with the compounds and methods described herein. In some embodiments, the compounds and compositions described herein are administered orally.

[00136] The terms "co-administration" or the like, as used herein, are meant to encompass administration of the selected therapeutic agents to a single patient, and are intended to include treatment regimens in which the agents are administered by the same or different route of administration or at the same or different time.

[00137] The terms "effective amount" or "therapeutically effective amount," as used herein, refer to a sufficient amount of an agent or a compound being administered, which will relieve to some extent one or more of the symptoms of the disease or condition being treated. The result includes reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an "effective amount" for therapeutic uses is the amount of the composition comprising a compound as disclosed herein required to provide a clinically significant decrease in disease symptoms. An appropriate "effective" amount in any individual case is optionally determined using techniques, such as a dose escalation study.

[00138] The terms "enhance" or "enhancing," as used herein, means to increase or prolong either in potency or duration a desired effect. Thus, in regard to enhancing the effect of therapeutic agents, the term "enhancing" refers to the ability to increase or prolong, either in potency or duration, the effect of other therapeutic agents on a system. An "enhancing-effective amount," as used herein, refers to an amount adequate to enhance the effect of another therapeutic agent in a desired system.

[00139] The term "pharmaceutical combination" as used herein, means a product that results from the mixing or combining of more than one active ingredient and includes both fixed and non-fixed combinations of the active ingredients. The term "fixed combination" means that the active ingredients, e.g. a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, and a co-agent, are both administered to a patient simultaneously in the form of a single entity or dosage. The term "non-fixed combination" means that the active ingredients, e.g. a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, and a co- agent, are administered to a patient as separate entities either simultaneously, concurrently or sequentially with no specific intervening time limits, wherein such administration provides effective levels of the two compounds in the body of the patient. The latter also applies to cocktail therapy, e.g. the administration of three or more active ingredients.

[00140] The terms "kit" and "article of manufacture" are used as synonyms.

[00141] The term "subject" or "patient" encompasses mammals. Examples of mammals include, but are not limited to, any member of the Mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. In one aspect, the mammal is a human.

[00142] The terms "treat," "treating" or "treatment," as used herein, include alleviating, abating or ameliorating at least one symptom of a disease or condition, preventing additional symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and/or therapeutically.

Pharmaceutical compositions [00143] In some embodiments, the compounds described herein are formulated into pharmaceutical compositions. Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable inactive ingredients that facilitate processing of the active compounds into preparations that are used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. A summary of pharmaceutical compositions described herein is found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa. : Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975;

Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkinsl999), herein incorporated by reference for such disclosure.

[00144] In some embodiments, the compounds described herein are administered either alone or in combination with pharmaceutically acceptable carriers, excipients or diluents, in a

pharmaceutical composition. Administration of the compounds and compositions described herein can be effected by any method that enables delivery of the compounds to the site of action. These methods include, though are not limited to delivery via enteral routes (including oral, gastric or duodenal feeding tube, rectal suppository and rectal enema), parenteral routes

(injection or infusion, including intraarterial, intracardiac, intradermal, intraduodenal,

intramedullary, intramuscular, intraosseous, intraperitoneal, intrathecal, intravascular,

intravenous, intravitreal, epidural and subcutaneous), inhalational, transdermal, transmucosal, sublingual, buccal and topical (including epicutaneous, dermal, enema, eye drops, ear drops, intranasal, and vaginal) administration, although the most suitable route may depend upon for example the condition and disorder of the recipient. By way of example only, compounds described herein can be administered locally to the area in need of treatment, by for example, local infusion during surgery, topical application such as creams or ointments, injection, catheter, or implant. The administration can also be by direct injection at the site of a diseased tissue or organ.

[00145] In some embodiments, pharmaceutical compositions suitable for oral administration are presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. In some embodiments, the active ingredient is presented as a bolus, electuary or paste.

[00146] Pharmaceutical compositions which can be used orally include tablets, push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with binders, inert diluents, or lubricating, surface active or dispersing agents. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. In some embodiments, the tablets are coated or scored and are formulated so as to provide slow or controlled release of the active ingredient therein. All formulations for oral administration should be in dosages suitable for such administration. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In some embodiments, stabilizers are added. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or Dragee coatings for identification or to characterize different combinations of active compound doses.

[00147] In some embodiments, pharmaceutical compositions are formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. The compositions may be presented in unit-dose or multi- dose containers, for example sealed ampoules and vials, and may be stored in powder form or in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, saline or sterile pyrogen-free water, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.

[00148] Pharmaceutical compositions for parenteral administration include aqueous and nonaqueous (oily) sterile injection solutions of the active compounds which may contain

antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.

[00149] Pharmaceutical compositions may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example, as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

[00150] For buccal or sublingual administration, the compositions may take the form of tablets, lozenges, pastilles, or gels formulated in conventional manner. Such compositions may comprise the active ingredient in a flavored basis such as sucrose and acacia or tragacanth.

[00151] Pharmaceutical compositions may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter, polyethylene glycol, or other glycerides.

[00152] Pharmaceutical compositions may be administered topically, that is by non-systemic administration. This includes the application of a compound of the present invention externally to the epidermis or the buccal cavity and the instillation of such a compound into the ear, eye and nose, such that the compound does not significantly enter the blood stream. In contrast, systemic administration refers to oral, intravenous, intraperitoneal and intramuscular administration.

[00153] Pharmaceutical compositions suitable for topical administration include liquid or semi- liquid preparations suitable for penetration through the skin to the site of inflammation such as gels, liniments, lotions, creams, ointments or pastes, and drops suitable for administration to the eye, ear or nose. The active ingredient may comprise, for topical administration, from 0.001% to 10%) w/w, for instance from 1%> to 2% by weight of the formulation.

[00154] Pharmaceutical compositions for administration by inhalation are conveniently delivered from an insufflator, nebulizer pressurized packs or other convenient means of delivering an aerosol spray. Pressurized packs may comprise a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. Alternatively, for administration by inhalation or insufflation, pharmaceutical preparations may take the form of a dry powder composition, for example a powder mix of the compound and a suitable powder base such as lactose or starch.

The powder composition may be presented in unit dosage form, in for example, capsules, cartridges, gelatin or blister packs from which the powder may be administered with the aid of an inhalator or insufflator.

[00155] It should be understood that in addition to the ingredients particularly mentioned above, the compounds and compositions described herein may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents.

Methods of Dosing and Treatment Regimens

[00156] In one embodiment, the compounds described herein, or a pharmaceutically acceptable salt, or solvate thereof, are used in the preparation of medicaments for the treatment of diseases or conditions in a mammal that would benefit from inhibition or reduction of LOXL2 activity. Methods for treating any of the diseases or conditions described herein in a mammal in need of such treatment, involves administration of pharmaceutical compositions that include at least one compound described herein or a pharmaceutically acceptable salt, active metabolite, prodrug, or pharmaceutically acceptable solvate thereof, in therapeutically effective amounts to said mammal.

[00157] In certain embodiments, the compositions containing the compound(s) described herein are administered for prophylactic and/or therapeutic treatments. In certain therapeutic

applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest at least one of the symptoms of the disease or condition. Amounts effective for this use depend on the severity and course of the disease or condition, previous therapy, the patient's health status, weight, and response to the drugs, and the judgment of the treating physician. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose escalation and/or dose ranging clinical trial.

[00158] In prophylactic applications, compositions containing the compounds described herein are administered to a patient susceptible to or otherwise at risk of a particular disease, disorder or condition. Such an amount is defined to be a "prophylactically effective amount or dose." In this use, the precise amounts also depend on the patient's state of health, weight, and the like. When used in patients, effective amounts for this use will depend on the severity and course of the disease, disorder or condition, previous therapy, the patient's health status and response to the drugs, and the judgment of the treating physician. In one aspect, prophylactic treatments include administering to a mammal, which previously experienced at least one symptom of the disease being treated and is currently in remission, a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, in order to prevent a return of the symptoms of the disease or condition. [00159] In certain embodiments wherein the patient's condition does not improve, upon the doctor's discretion the administration of the compounds are administered chronically, that is, for an extended period of time, including throughout the duration of the patient's life in order to ameliorate or otherwise control or limit the symptoms of the patient's disease or condition.

[00160] In certain embodiments wherein a patient's status does improve, the dose of drug being administered is temporarily reduced or temporarily suspended for a certain length of time (i.e., a "drug holiday"). In specific embodiments, the length of the drug holiday is between 2 days and 1 year, including by way of example only, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, or more than 28 days. The dose reduction during a drug holiday is, by way of example only, by 10%-100%, including by way of example only 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, and 100%.

[00161] Once improvement of the patient's conditions has occurred, a maintenance dose is administered if necessary. Subsequently, in specific embodiments, the dosage or the frequency of administration, or both, is reduced, as a function of the symptoms, to a level at which the improved disease, disorder or condition is retained. In certain embodiments, however, the patient requires intermittent treatment on a long-term basis upon any recurrence of symptoms.

[00162] The amount of a given agent that corresponds to such an amount varies depending upon factors such as the particular compound, disease condition and its severity, the identity (e.g., weight, sex) of the subject or host in need of treatment, but nevertheless is determined according to the particular circumstances surrounding the case, including, e.g., the specific agent being administered, the route of administration, the condition being treated, and the subject or host being treated.

[00163] In general, however, doses employed for adult human treatment are typically in the range of 0.01 mg-5000 mg per day. In one aspect, doses employed for adult human treatment are from about 1 mg to about 1000 mg per day. In one embodiment, the desired dose is conveniently presented in a single dose or in divided doses administered simultaneously or at appropriate intervals, for example as two, three, four or more sub-doses per day.

[00164] In one embodiment, the daily dosages appropriate for the compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, are from about 0.01 to about 50 mg/kg per body weight. In some embodiments, the daily dosage or the amount of active in the dosage form are lower or higher than the ranges indicated herein, based on a number of variables in regard to an individual treatment regime. In various embodiments, the daily and unit dosages are altered depending on a number of variables including, but not limited to, the activity of the compound used, the disease or condition to be treated, the mode of administration, the requirements of the individual subject, the severity of the disease or condition being treated, and the judgment of the practitioner.

[00165] Toxicity and therapeutic efficacy of such therapeutic regimens are determined by standard pharmaceutical procedures in cell cultures or experimental animals, including, but not limited to, the determination of the LD 50 and the ED 50 . The dose ratio between the toxic and therapeutic effects is the therapeutic index and it is expressed as the ratio between LD 50 and ED 50 . In certain embodiments, the data obtained from cell culture assays and animal studies are used in formulating the therapeutically effective daily dosage range and/or the therapeutically effective unit dosage amount for use in mammals, including humans. In some embodiments, the daily dosage amount of the compounds described herein lies within a range of circulating concentrations that include the ED 50 with minimal toxicity. In certain embodiments, the daily dosage range and/or the unit dosage amount varies within this range depending upon the dosage form employed and the route of administration utilized.

[00166] In any of the aforementioned aspects are further embodiments in which the effective amount of the compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is: (a) systemically administered to the mammal; and/or (b) administered orally to the mammal; and/or (c) intravenously administered to the mammal; and/or (d) administered by injection to the mammal; and/or (e) administered topically to the mammal; and/or (f)

administered non-systemically or locally to the mammal.

[00167] In any of the aforementioned aspects are further embodiments comprising single administrations of the effective amount of the compound, including further embodiments in which (i) the compound is administered once a day; or (ii) the compound is administered to the mammal multiple times over the span of one day.

[00168] In any of the aforementioned aspects are further embodiments comprising multiple administrations of the effective amount of the compound, including further embodiments in which (i) the compound is administered continuously or intermittently: as in a single dose; (ii) the time between multiple administrations is every 6 hours; (iii) the compound is administered to the mammal every 8 hours; (iv) the compound is administered to the mammal every 12 hours; (v) the compound is administered to the mammal every 24 hours. In further or alternative

embodiments, the method comprises a drug holiday, wherein the administration of the compound is temporarily suspended or the dose of the compound being administered is temporarily reduced; at the end of the drug holiday, dosing of the compound is resumed. In one embodiment, the length of the drug holiday varies from 2 days to 1 year.

[00169] In certain instances, it is appropriate to administer at least one compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, in combination with one or more other therapeutic agents. In certain embodiments, the pharmaceutical composition further comprises one or more anti -cancer agents.

[00170] In one embodiment, the therapeutic effectiveness of one of the compounds described herein is enhanced by administration of an adjuvant (i.e., by itself the adjuvant has minimal therapeutic benefit, but in combination with another therapeutic agent, the overall therapeutic benefit to the patient is enhanced). Or, in some embodiments, the benefit experienced by a patient is increased by administering one of the compounds described herein with another agent (which also includes a therapeutic regimen) that also has therapeutic benefit.

[00171] In one specific embodiment, a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is co-administered with a second therapeutic agent, wherein the compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, and the second therapeutic agent modulate different aspects of the disease, disorder or condition being treated, thereby providing a greater overall benefit than administration of either therapeutic agent alone.

[00172] In any case, regardless of the disease, disorder or condition being treated, the overall benefit experienced by the patient may be additive of the two therapeutic agents or the patient may experience a synergistic benefit.

[00173] In certain embodiments, different therapeutically-effective dosages of the compounds disclosed herein will be utilized in formulating pharmaceutical composition and/or in treatment regimens when the compounds disclosed herein are administered in combination with one or more additional agent, such as an additional therapeutically effective drug, an adjuvant or the like. Therapeutically-effective dosages of drugs and other agents for use in combination treatment regimens is optionally determined by means similar to those set forth hereinabove for the actives themselves. Furthermore, the methods of prevention/treatment described herein encompasses the use of metronomic dosing, i.e., providing more frequent, lower doses in order to minimize toxic side effects. In some embodiments, a combination treatment regimen

encompasses treatment regimens in which administration of a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is initiated prior to, during, or after treatment with a second agent described herein, and continues until any time during treatment with the second agent or after termination of treatment with the second agent. It also includes treatments in which a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, and the second agent being used in combination are administered simultaneously or at different times and/or at decreasing or increasing intervals during the treatment period. Combination treatment further includes periodic treatments that start and stop at various times to assist with the clinical management of the patient. [00174] It is understood that the dosage regimen to treat, prevent, or ameliorate the condition(s) for which relief is sought, is modified in accordance with a variety of factors (e.g. the disease, disorder or condition from which the subject suffers; the age, weight, sex, diet, and medical condition of the subject). Thus, in some instances, the dosage regimen actually employed varies and, in some embodiments, deviates from the dosage regimens set forth herein.

[00175] For combination therapies described herein, dosages of the co-administered compounds vary depending on the type of co-drug employed, on the specific drug employed, on the disease or condition being treated and so forth. In additional embodiments, when co-administered with one or more other therapeutic agents, the compound provided herein is administered either simultaneously with the one or more other therapeutic agents, or sequentially.

[00176] In combination therapies, the multiple therapeutic agents (one of which is one of the compounds described herein) are administered in any order or even simultaneously. If administration is simultaneous, the multiple therapeutic agents are, by way of example only, provided in a single, unified form, or in multiple forms (e.g., as a single pill or as two separate pills).

[00177] The compounds described herein, or a pharmaceutically acceptable salt, or solvate thereof, as well as combination therapies, are administered before, during or after the occurrence of a disease or condition, and the timing of administering the composition containing a compound varies. Thus, in one embodiment, the compounds described herein are used as a prophylactic and are administered continuously to subjects with a propensity to develop conditions or diseases in order to prevent the occurrence of the disease or condition. In another embodiment, the compounds and compositions are administered to a subject during or as soon as possible after the onset of the symptoms. In specific embodiments, a compound described herein is administered as soon as is practicable after the onset of a disease or condition is detected or suspected, and for a length of time necessary for the treatment of the disease. In some

embodiments, the length required for treatment varies, and the treatment length is adjusted to suit the specific needs of each subject. For example, in specific embodiments, a compound described herein or a formulation containing the compound is administered for at least 2 weeks, about 1 month to about 5 years.

EXAMPLES

[00178] The following examples are provided for illustrative purposes only and not to limit the scope of the claims provided herein.

[00179] LOXL-2 inhibitor compounds for use in the methods of treatment described herein include, but are not limited to, those compounds described in International patent application no. PCT/US2016/020731 titled "Lysysl Oxidase-Like 2 Inhibitors and Uses Thereof filed on March 3, 2016; International patent application no. PCT/US2016/020732 titled "Fluorinated Lysyl Oxidase-Like 2 Inhibitors and Uses Thereof filed on March 3, 2016; International patent application no. PCT/US2016/039253 titled "Lysysl Oxidase-Like 2 Inhibitors and Uses Thereof filed on June 24, 2016; International patent application no. PCT/US2016/042826 titled "Lysyl Oxidase-like 2 (LOXL2) Inhibitors and Uses Thereof filed on July 18, 2016; International patent application no. PCT/US2017/016847 titled "Quinolinone Lysyl Oxidase-Like 2 Inhibitors and Uses Thereof filed on February 7, 2017; each of which is herein incorporated by reference for such compounds.

Example A-l: Parenteral Pharmaceutical Composition

[00180] To prepare a parenteral pharmaceutical composition suitable for administration by injection (subcutaneous, intravenous), 1-1000 mg of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, is dissolved in sterile water and then mixed with 10 mL of 0.9% sterile saline. A suitable buffer is optionally added as well as optional acid or base to adjust the pH. The mixture is incorporated into a dosage unit form suitable for administration by injection

Example A-2: Oral Solution

[00181] To prepare a pharmaceutical composition for oral delivery, a sufficient amount of a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is added to water (with optional solubilizer(s),optional buffer(s) and taste masking excipients) to provide a 20 mg/mL solution.

Example A-3: Oral Tablet

[00182] A tablet is prepared by mixing 20-50% by weight of a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, 20-50% by weight of microcrystalline cellulose, 1-10% by weight of low-substituted hydroxypropyl cellulose, and 1-10% by weight of magnesium stearate or other appropriate excipients. Tablets are prepared by direct compression. The total weight of the compressed tablets is maintained at 100 -500 mg.

Example A-4: Oral Capsule

[00183] To prepare a pharmaceutical composition for oral delivery, 1-1000 mg of a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is mixed with starch or other suitable powder blend. The mixture is incorporated into an oral dosage unit such as a hard gelatin capsule, which is suitable for oral administration.

[00184] In another embodiment, 1-1000 mg of a compound described herein, or a

pharmaceutically acceptable salt, or solvate thereof, is placed into Size 4 capsule, or size 1 capsule (hypromellose or hard gelatin) and the capsule is closed.

Example A-5: Topical Gel Composition

[00185] To prepare a pharmaceutical topical gel composition, a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is mixed with hydroxypropyl cellulose, propylene glycol, isopropyl myristate and purified alcohol USP. The resulting gel mixture is then incorporated into containers, such as tubes, which are suitable for topical administration.

Example B-l: Human LOXL2 Amine Oxidase Activity Assay

[00186] LOXL2 amine oxidase activity is evaluated by measuring Amplex Red fluorescence using 10-20X concentrated conditioned media from CHO cells stably expressing human LOXL2. To assay for amine oxidase activity, 10 μΐ ^ of the concentrated conditioned media is incubated with 2 μΙ_, of test compound in DMSO and 73 μΐ ^ Assay Buffer (50 mM Borate Buffer, pH8) for 2h at 37 °C. After the 2h incubation, 5 μΙ_, of 10 mM 1,5-Diaminopentane (DAP) diluted in Assay Buffer and 10 μΐ of Amplex Red Mix (8.5 μΐ Assay Buffer + 0.5 μΐ of 10 mM Amplex Red + 1 μΐ of 500 U/ml Horseradish Peroxidase) are added and the plate mixed and immediately placed on the FlexStaion for fluorescence measurements. Fluorescence is read in kinetic mode every 2 min for 1 hour at excitation = 544 and emission = 590. The amine oxidase activity is calculated from the slope of the linear portion of the curve.

Example B-2: LOXL2 Human Blood Amine Oxidase Activity Assay

[00187] The amine oxidase activity of human LOXL2 in the context of human whole blood is measured using an Amplex Red assay. Human, recombinant LOXL2 (purchased from Sino Biologicals, Beijing, China) is added to human blood collected in heparin vacutainer tubes.

Briefly, 0.5-2 μg recombinant, human LOXL2 (reconstituted in water) and 2 μΐ test compound in DMSO is added to 192 μΐ blood, mixed and incubated at 37°C for 2h. After the 2h incubation, the blood is centrifuged at 2000 x g for 15 min at room temperature to isolate the plasma. 50 μΐ of plasma is removed and mixed with 25 μΐ of 40 mM DAP (diluted in water) and 25 μΐ Amplex Red Mix (23.5 μΐ 50 mM Borate Buffer, pH8 + 0.5 μΐ 10 mM Amplex Red + 1 μΐ 500U/ml Horseradish Peroxidase). Samples are mixed and immediately placed on the FlexStation for fluorescence measurements. Fluorescence is read in kinetic mode every 2 min for 1 hour at excitation = 544 and emission = 590. The amine oxidase activity is calculated from the slope of the linear portion of the curve.

Example B-3: The Effect of LOXL2 Inhibitors on Fibroblast-like Synoviocyte (FLS) Invasion

[00188] The effects of LOXL2 inhibitor compounds will be examined in an FLS invasion study. The FLS invasion study is a two-chamber model where cells invade through Matrigel. This in vitro assay correlates with joint damage in vivo (Tolboom TC, et al. Invasiveness of fibroblast- like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis. Arthritis Rheum 52: 1999-2002 (2005)).

[00189] Briefly, FLS cell lines (RA and rodent FLS cell lines) are placed on the upper chamber. Over a 24 hour period cells invade through the Matrigel layer then go through pores at the base of the upper chamber. The bottom of the upper chamber is stained and cells counted.

[00190] The experiment is repeated but now the FLS cell lines are pre-treated with increasing concentrations of LOXL2 inhibitor compound. For example, the cell lines are pretreated with LOXL2 inhibitor compound for about 1-2 hours to allow for efficient binding by the compound and then placed in the upper chamber over the Matrigel layer.

Example B-4: Collagen-induced arthritis (CIA) model system

[00191] A non-limiting example of the effects of LOXL2 inhibitor compounds is described below.

[00192] In this example, the effect of LOXL2 inhibitors on development of collagen-induced arthritis in a mouse model system is assessed. The DBA/1 mouse strain is used, as it is highly susceptible to CIA. On day 0 and day 21, all animals are subjected to an intradermal injection into the tail of 200 μg of collagen in 0.1 ml of a Type II collagen/Complete Freund's Adjuvant (CFA) emulsion. The location of the injection is at an approximate caudal distance of 1 cm from the base of the tail.

[00193] Male DBA/1 mice, at 6-7 weeks of age, all within +20% of mean weight, are randomly assigned to one of three treatment groups. Group 1 is a vehicle control group. The animals in this group receive 10 ml/kg of vehicle (0.5% methyl cellulose), orally (PO), once daily, from Day 16. Animals in Group 2, a positive control group, receive 0.05 mg/kg dexamethasone at 10 ml/kg, PO, once daily from Day 16. Animals in Group 3 receive 0.5-60 mg/kg LOXL2 inhibitor compound, once or twice per day from Day 16. The study is terminated on Day 35 and all remaining animals are bled to exansanguination under isofluorane followed by cervical dislocation.

[00194] Mice are examined for signs of arthritogenic responses in peripheral joints on Days 0 and 16, and thereafter daily until conclusion of the study. Arthritic reactions are graded, for each paw, on an ascending scale of severity, as follows:

Grade 0: No reaction, normal.

Grade 1 : Two hind or forepaw joints affected or mild diffuse erythema and swelling.

Grade 2: Three hind or forepaw joints affected or moderate diffuse erythema and swelling Grade 3 : Four hind or forepaw joints affected or marked diffuse erythema and swelling

Grade 4: Entire paw affected, severe diffuse erythema and severe swelling, unable to flex digits

[00195] Clinical examinations are carried out on Day 0, Day 16 and daily thereafter.

Observations include changes in skin, fur, eyes, mucous membranes, occurrence of secretions and excretions (e.g., diarrhea) and autonomic activity (e.g., lachrymation, salivation, piloerection, pupil size, and unusual respiratory pattern). Changes in gait, posture, and response to handling, as well as bizarre behaviors, tremors, convulsions, sleep and coma are also noted.

[00196] Animals are weighed shortly before tail injection on Day 0, again on Day 16, and thereafter three times weekly until termination of the study.

[00197] As an indication of experimental arthritis, the thicknesses of both hind paws are measured on Day 0, Day 16, and daily thereafter. Left and right paws are measured dorso- ventrally just above the toes and below the calcaneum, using a dial caliper (Kroeplin, Munich, Germany).

[00198] At the termination of the study, on Day 35, paws from all remaining animals are removed, skinned and fixed in 10% neutral buffered formalin. Thin sections are analyzed histologically by H&E staining for inflammation, pannus formation, cartilage damage and bone resorption.

[00199] Evaluation of data, to determine the significance of any observed effects, is based primarily on comparison of the mean group values for arthritis scores, body weight, and paw thickness measurements (all as described above) by ANOVA followed by Tukey post -hoc analysis (Winsat 2005.1 for Excel).

[00200] The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims.