6-6 Fused bicyclic heteroaryl compounds and their use as LATS inhibitors

Abstract

The present invention relates to 6-6 fused bicyclic heteroaryl compounds and their use as LATS inhibitors, in particular to 6-6 fused bicyclic heteroaryl compounds having formula A2 or A1 and their use as LATS inhibitors, or salts, stereoisomers or pharmaceutical compositions thereof; wherein the variables are as defined herein (A1 & A2). The present invention further relates to methods for inhibiting LATS in cell populations using compounds having formula A1 or salts, stereoisomers or pharmaceutical compositions thereof. The present invention further provides methods for preparing the compounds of the present invention and their therapeutic uses. The present invention further provides methods for preparing the compounds of the present invention, methods for the medical use of the compounds of the present invention, and uses of the compounds of the present invention in the treatment and management of diseases or disorders. #imgabs0#

Description

[0001] The applicant filed PCT application No. PCT / IB2018 / 052919 on April 26, 2018, entitled "6-6 Fused Bicyclic Heteroaryl Compounds and Their Use as LATS Inhibitors." This PCT application entered the Chinese national phase on October 25, 2019, with application number 201880027586.7. The present application is a divisional application of that Chinese application.

[0002] Sequence Listing

[0003] This application contains a sequence listing filed electronically in ASCII format and hereby incorporated by reference in its entirety. The ASCII copy was created on April 23, 2018, is named PAT057699-WO-PCT_SL.txt and is 35,778 bytes in size. Technical Field

[0004] The present invention relates to LATS (Large Tumor Suppressor Kinase) inhibitors. The present invention further relates to 6-6 fused bicyclic heteroaryl compounds and compositions comprising such compounds.

[0005] The present invention also relates to the use of these compounds in vitro for the production of cellular materials for cell therapy / transplantation. The present invention further relates to methods for producing expanded cell populations, such as expanded ocular cell populations, such as those comprising limbal stem cells (LSCs) or corneal endothelial cells (CECs) (involving the use of LATS inhibitors), as well as cell populations, such as ocular cells (including limbal stem cells (LSCs) or corneal endothelial cells (CECs)), and formulations, uses and methods of therapy comprising said cells.

[0006] The present invention also relates to 6-6 fused bicyclic heteroaryl compounds, compositions containing such compounds, and their use in promoting wound healing, in particular for treating burns, acute and chronic skin ulcers, including vascular, diabetic and pressure ulcers, such as venous leg ulcers, diabetic foot ulcers, and pressure ulcers.

[0007] The present invention also relates to 6-6 fused bicyclic heteroaryl compounds, compositions comprising such compounds, and their use in liver regeneration and liver regeneration, as well as in preventing isolated organ damage and maintaining or improving isolated organ function with or without a perfusion device. Background Art

[0008] Organ regeneration and / or healing are key issues in treating many serious health problems.

[0009] For example, in the eye, corneal blindness is known to be the third leading cause of blindness worldwide, and approximately half of all corneal transplants performed worldwide are for the treatment of corneal endothelial dysfunction.

[0010] The cornea is a transparent tissue composed of distinct layers: the corneal epithelium, Bowman's membrane, stroma, Descemet's membrane, and endothelium. The corneal endothelium also comprises a single layer of human corneal endothelial cells and helps maintain corneal transparency through their barrier and ion pump functions. It plays a vital role in maintaining the balance of fluids, nutrients, and salts between the corneal stroma and the aqueous humor. To maintain transparency, endothelial cell density must be maintained, but it can decrease significantly due to trauma, disease, or endothelial dystrophy. Cell density also decreases with aging. The human corneal endothelium has a limited tendency to proliferate in vivo. If cell density decreases too low, barrier function may be compromised. Loss of endothelial barrier function leads to corneal edema and vision loss. The clinical condition of bullous keratopathy may be a complication of this condition.

[0011] Currently, the only treatment for blindness caused by corneal endothelial dysfunction is corneal transplantation. Although corneal transplantation is one of the most common forms of organ transplantation, the availability of donor corneas is extremely limited. A global survey from 2012 to 2013 quantified the severe shortage of corneal transplant tissue, finding that only one cornea was available for every 70 requests (Gain et al. (2016) Global Survey of Corneal Transplantation and Eye Banking. JAMA Ophthalmol. 134:167-173).

[0012] Therefore, new therapeutic approaches to provide corneal endothelial cells for the treatment of corneal endothelial dysfunction are highly desirable.

[0013] The corneal epithelium also needs to be maintained in the eye. The corneal epithelium is composed of a layer of basal cells and multiple layers of non-keratinized, stratified squamous epithelium. This is essential for maintaining the clarity and regular refractive surface of the cornea. It acts as a transparent, renewable protective layer on the corneal stroma and is replenished by a population of stem cells located at the limbus. In limbal stem cell deficiency (a condition in which the limbus stem cells are diseased or absent), the number of healthy limbal stem cells decreases, resulting in a reduced ability of the corneal epithelium to renew itself.

[0014] Limbal stem cell deficiency can be caused by chemical or thermal burns, damage from ultraviolet and ionizing radiation, or even contact lens wear; genetic disorders (such as aniridia) and immune disorders (such as Stevens Johnson syndrome and ocular cicatricial pemphigus). Limbal stem cell loss can be partial or complete and can be unilateral or bilateral. Symptoms of limbal stem cell deficiency include pain, photophobia, incurable and painful corneal epithelial defects, corneal neovascularization, replacement of the corneal epithelium by the conjunctival epithelium, loss of corneal transparency that can ultimately lead to blindness, and decreased visual acuity.

[0015] A product for treating limbal stem cell deficiency (named ) received conditional marketing authorization in the European Union in 2015, making it the first advanced therapeutic medicine (ATMP) in Europe containing stem cells. Holoclar is an ex vivo expanded preparation of autologous human corneal epithelial cells containing stem cells. A healthy limbal tissue biopsy is taken from the patient, expanded ex vivo and frozen until surgery. To be administered to the patient, the thawed cells are grown on a membrane containing fibrin and then surgically implanted into the patient's eye. The therapy is intended for adults with moderate to severe limbal stem cell deficiency due to physical or chemical eye burns. (Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G. (2010) Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 363: 147-155). However, limitations of this approach are that it is intended for autologous use only, and sufficient viable limbus must be present in one eye to allow for the removal of at least 1–2 square millimeters of undamaged tissue from the patient. For each specific patient, there is also the risk that their cells may not be successfully cultured and that the patient may not be able to undergo this treatment. Furthermore, murine feeder cells are used to prepare Holoclar cell preparations, which introduce potential safety concerns for human use due to the risk of disease transmission and potential immunogenicity. Furthermore, Holoclar cell preparations contain only approximately 5% limbal stem cells, as identified by p63α staining.

[0016] Therefore, new therapeutic approaches to supply limbal stem cells to treat limbal stem cell deficiency are urgently needed.

[0017] Functional liver regeneration in both steady-state and disease states is crucial for maintaining essential physiological processes. Although the liver has remarkable regenerative potential, this process can be impaired following severe acute or chronic liver injury. Liver injury and impaired liver regeneration often lead to significant morbidity and mortality, necessitating life-saving liver transplantation. Unfortunately, the current demand for liver transplantation far outstrips the supply of available donor organs. As a result, many patients continue to die while awaiting a life-saving transplant. The use of open-liver transplantation from deceased donors or partial liver transplantation from living donors is limited by graft size. Transplantation of partial livers with an inadequate graft-to-recipient weight ratio (GRWR) increases the incidence of graft dysfunction and failure. Therapies that increase liver regeneration may allow the transplantation of portions of the liver that would otherwise be considered inadequate for transplantation based on size. Alternatively, regenerating the liver by inhibiting hepatocyte death, improving liver function, and repairing abnormal liver architecture can normalize liver function, thereby obviating the need for transplantation (Forbes SJ and Newsome PN (2016) Liver regeneration-mechanisms and models to clinical application. Nature Reviews Gastroenterology & Hepatology, 13(8):473-485; Dutkowski P, Linecker M, DeOliveira ML, Müllhaupt B, Clavien PA (2015) Challenges to Liver Transplantation and Strategies to Improve Outcomes. Gastroenterology, 148(2):307-323).

[0018] Therefore, more effective therapies to promote liver regeneration are urgently needed.

[0019] Chronic skin ulcers, including vascular, diabetic, and pressure ulcers, constitute a major public health problem. The increased demand for wound care is reflected in the association of wounds with comorbidities, increased mortality, and decreased quality of life for patients (Demidova-Rice TN, Hamblin MR, & Herman IM (2012) Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care. Advances in skin & wound care 25(7):304-314; Demidova-Rice TN, Hamblin MR, & Herman IM (2012) Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: role of growth factors in normal and pathological wound healing: therapeutic potential and methods of Acute and impaired wound healing: pathophysiology and current drug delivery methods, Part 2: Role of growth factors in normal and pathological wound healing: therapeutic potential and delivery methods. Advances in skin & wound care 25(8):349-370). In the United States alone, the healthcare cost of patients with chronic wounds is approximately $25 billion annually.No new chemical entities have been approved by the FDA since the approval of Regranex (PDGF) in 1997, and Regranex has limited efficacy (Eaglstein WH, Kirsner RS, and Robson MC (2012) Food and Drug Administration (FDA) drug approval end points for chronic cutaneous ulcer studies. Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society 20(6):793-796). Intrinsically, growth factors are unstable in the proteolytic environment of the wound bed. Growth factor therapy may also suffer from low expression of its corresponding receptors in wounds, as shown in clinical patient samples (Demidova-Rice TN, Hamblin MR, & Herman IM (2012) Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: role of growth factors in normal and pathological wound healing: therapeutic potential and methods of delivery. Advances in skin & wound care 25(8):349-370).

[0020] Therefore, more effective therapies are urgently needed to promote wound healing in patients with chronic wounds.

[0021] Therefore, new treatments to promote cell proliferation are urgently needed for conditions that affect a range of organs throughout the body, such as the eye, liver, and skin. Summary of the Invention

[0022] This invention relates to compounds, their salts, and compositions thereof, wherein the compounds are LATS (large tumor suppressor kinase) inhibitors. These compounds can be used in the treatment of the aforementioned conditions and purposes.

[0023] Various aspects of the invention are described herein.

[0024] This invention relates to compounds having the formula A2 or its derivatives, or their salts or stereoisomers.

[0025]

[0026] where X 1 , Ring A, R 1 、R 2 、R 3 and R 5 As defined below in the detailed description.

[0027] In a preferred embodiment, the compound is a compound or a salt thereof according to Formula I or Formula II or a subform thereof:

[0028]

[0029] Among them, ring A, R 1 、R 2 、R 3 and R 5 As defined below in the detailed description.

[0030] In another aspect, the present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound according to the definition of formula A2 or its subformulae, or a pharmaceutically acceptable salt thereof, or its subformulae, and one or more pharmaceutically acceptable carriers.

[0031] In another aspect, the present invention relates to a combination, in particular a pharmaceutical combination, comprising a therapeutically effective amount of a compound according to the definition of formula A2 or its subformulae, or a pharmaceutically acceptable salt thereof, and one or more therapeutically active agents.

[0032] In another respect, the present invention relates to compounds and compositions that can be used in therapy.

[0033] In one embodiment, the present invention relates to a method for inhibiting LATS in cells or cell populations using a compound of formula A1 or a derivative thereof, a salt thereof, or a stereoisomer thereof:

[0034]

[0035] where X 1 、X 2 , Ring A, R 1 、R 2 、R 3 and R5 As defined in detail below. Preferably, the salt is a pharmaceutically acceptable salt. In a specific embodiment of the method for inhibiting LATS in a cell population according to the present invention, the compound or its salt is selected from 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine. According to another specific embodiment of the method for inhibiting LATS in a cell population according to the present invention, the compound or its salt is selected from N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0036] In another embodiment, the present invention relates to a method of inhibiting LATS in an ocular cell population using a compound of formula A1 or its subformulae, or a salt thereof, or a stereoisomer thereof. In yet another embodiment, the present invention relates to a method of inhibiting LATS in a cell population comprising limbal stem cells using a compound of formula A1 or its subformulae, or a salt thereof, or a stereoisomer thereof. In yet another embodiment, the present invention relates to a method of inhibiting LATS in a cell population comprising corneal endothelial cells using a compound of formula A1 or its subformulae, or a salt thereof, or a stereoisomer thereof.

[0037] Also preferably, the method of inhibiting LATS in a cell population is performed ex vivo. In yet another preferred embodiment, the compound is present at a concentration of 0.5 to 100 micromolar, preferably 0.5 to 25 micromolar, more preferably 1 to 20 micromolar, and particularly preferably about 3 to 10 micromolar. In a preferred embodiment of the method of inhibiting LATS in a cell population comprising limbal stem cells, the compound is present for 12 to 16 days, particularly preferably 14 days. In another embodiment of the method of inhibiting LATS in a cell population comprising corneal endothelial cells, the compound is present for one to two weeks, and the cells are then cultured in growth medium not supplemented with the compound for a period of time, preferably, wherein the period is one to two weeks. In one embodiment of the method of inhibiting LATS in a cell population, the LATS inhibitor inhibits LATS1 or LATS2, or both LATS1 and LATS2. In a more preferred embodiment, the LATS inhibitor inhibits both LATS1 and LATS2. In another preferred embodiment of the method of inhibiting LATS in a cell population comprising limbal stem cells, the method further comprises genetically modifying the limbal stem cells. In another preferred embodiment of the method for inhibiting LATS in a cell population comprising corneal endothelial cells, the method further comprises genetically modifying the corneal endothelial cells. Preferably, the genetic modification comprises introducing a gene editing system into the cells that specifically targets genes associated with promoting a host anti-transplantation immune response. In yet another preferred embodiment, the method for inhibiting LATS in a cell population comprises a further step of rinsing the cells after generating the expanded cell population to substantially remove the compound according to the present invention. In one aspect, the present invention relates to an expanded cell population comprising limbal stem cells obtainable by the method for inhibiting LATS in a cell population comprising limbal stem cells according to the present invention. In another aspect, the present invention relates to an expanded cell population comprising limbal stem cells obtained by the method for inhibiting LATS in a cell population comprising limbal stem cells according to the present invention. In one aspect, the present invention relates to a corneal endothelial cell population obtainable by the method for inhibiting LATS in a cell population comprising corneal endothelial cells according to the present invention. In another aspect, the present invention relates to a corneal endothelial cell population obtained by the method for inhibiting LATS in a cell population comprising corneal endothelial cells according to the present invention. In another aspect, the present invention relates to an ocular cell delivery formulation comprising a cell population obtainable or obtained by a method for inhibiting LATS according to the present invention and a composition suitable for ocular delivery as a positioning agent. In a specific embodiment, the positioning agent is GelMa (which is methacrylamide-modified gelatin, also known as methacrylated gelatin). In another specific embodiment, the positioning agent is fibrin or fibrin glue. Preferably, the cell delivery formulation for limbal stem cells has greater than 20% limbal stem cells. It is also preferred that the cell delivery formulation for limbal stem cells has greater than 20% p63α-positive cells.In certain preferred aspects, the cell populations obtained or acquired by the method for inhibiting LATS according to the present invention, or the cell delivery formulation according to the present invention, contain only trace levels of the compound according to the present invention. Preferably, in the cell delivery formulation for corneal endothelial cells, the density of corneal endothelial cells in the cell delivery formulation is greater than 500 cells / mm². 2 (Area). In some preferred aspects, the cell population obtained or obtained by the method of inhibiting LATS according to the present invention, or the cell delivery formulation according to the present invention, contains only trace levels of the compound according to the present invention.

[0038] In another aspect, the present invention relates to a method for culturing cells, comprising culturing a cell population in the presence of a LATS inhibitor. The cells may be a cell population described and / or provided herein. Preferably, the cells are ocular cells or hepatocytes. In a preferred embodiment, the cells are ocular cells. In another aspect, the present invention relates to a method for culturing cells, comprising culturing a cell population comprising limbal stem cells in the presence of a LATS inhibitor. In another aspect, the present invention relates to a method for culturing cells, comprising culturing a cell population comprising corneal endothelial cells in the presence of a LATS inhibitor. In a preferred embodiment, the present invention relates to a method for culturing cells, comprising culturing a cell population comprising limbal stem cells, wherein the LATS inhibitor is a compound according to the present invention having Formula A1 or a subformula thereof, or a salt thereof. In another preferred embodiment, the present invention relates to a method for culturing cells, comprising culturing a cell population comprising corneal endothelial cells, wherein the LATS inhibitor is a compound according to the present invention having Formula A1 or a subformula thereof, or a salt thereof. Preferably, the salt is a pharmaceutically acceptable salt. In a preferred embodiment, the compound is present at a concentration of 0.5 to 100 micromolar, preferably 0.5 to 25 micromolar, more preferably 1 to 20 micromolar, and particularly preferably about 3 to 10 micromolar. In a preferred embodiment of the method for culturing cells (including culturing a cell population comprising limbal stem cells), the compound is present for 12 to 16 days, particularly preferably for 14 days. In a preferred embodiment of the method for culturing cells (including culturing a cell population comprising corneal endothelial cells), the compound is present for one to two weeks, and the cells are then cultured for a period of time in growth medium not supplemented with the compound, preferably, wherein the period is one to two weeks. In one embodiment of the present invention, the LATS inhibitor inhibits LATS1 or LATS2, or LATS1 and LATS2. In a more preferred embodiment, the LATS inhibitor inhibits LATS1 and LATS2. In one embodiment, the method further comprises genetically modifying the cells. Preferably, the genetic modification comprises introducing a gene editing system into the cells, wherein the gene editing system specifically targets genes associated with promoting a host anti-transplantation immune response. Preferably, the cells are ocular cells. In one embodiment, the method further comprises genetically modifying limbal stem cells. In another preferred embodiment, the method further comprises genetically modifying corneal endothelial cells. In yet another preferred embodiment, the method for culturing cells comprises a further step of rinsing the cells after producing the expanded cell population to substantially remove the compound according to the present invention. In one aspect, the present invention relates to an expanded cell population obtainable by a method of culturing cells according to the present invention. In another aspect, the present invention relates to an expanded cell population obtainable by a method of culturing cells according to the present invention. Preferably, the cells are ocular cells.

[0039] In one aspect, the present invention relates to an expanded cell population comprising limbal stem cells obtainable by a method of culturing cells comprising limbal stem cells according to the present invention. In another aspect, the present invention relates to an expanded cell population comprising limbal stem cells obtainable by a method of culturing cells comprising limbal stem cells according to the present invention. In one aspect, the present invention relates to a population of corneal endothelial cells obtainable by a method of culturing cells comprising corneal endothelial cells according to the present invention. In another aspect, the present invention relates to a population of corneal endothelial cells obtainable by a method of culturing cells comprising corneal endothelial cells according to the present invention. In another aspect, the present invention relates to an ocular cell delivery formulation comprising a cell population obtainable or obtained by a method of culturing cells according to the present invention and a composition suitable for ocular delivery as a positioning agent. In a specific embodiment, the positioning agent is GelMa. In another specific embodiment, the positioning agent is fibrin or fibrin glue. Preferably, the cell delivery formulation of limbal stem cells has more than 20% limbal stem cells. It is also preferred that the cell delivery formulation of limbal stem cells has more than 20% p63α positive cells. Preferably, the corneal endothelial cells are present at a density of greater than 500 cells / mm 2 In certain preferred aspects, the cell population obtainable or obtained by the method of culturing cells according to the present invention or the cell delivery formulation according to the present invention has only trace levels of the compound according to the present invention.

[0040] In another aspect, the present invention relates to a method for expanding a cell population, comprising the steps of: a) culturing a seeded cell population in the presence of a LATS inhibitor to produce an expanded cell population. In a preferred embodiment, the cell population expansion method is performed ex vivo. Preferably, the cells are ocular cells or hepatocytes. In a preferred embodiment, the cells are ocular cells. In yet another aspect, the present invention relates to a method for expanding a cell population, comprising the steps of: a) culturing a seeded cell population comprising limbal stem cells in the presence of a LATS inhibitor to produce an expanded cell population comprising limbal stem cells. Preferably, the LATS inhibitor is a compound according to the present invention having Formula A1 or a subformula thereof, or a salt thereof. In another aspect, the present invention relates to a method for expanding a cell population, comprising the steps of: a) culturing a seeded cell population comprising limbal stem cells in the presence of a compound having Formula A1 or a subformula thereof, or a salt thereof, to produce an expanded cell population comprising limbal stem cells. In another embodiment of the present invention, the compound is selected from Formula A2 or a subformula thereof, or a salt thereof. In another aspect, the present invention relates to a method for expanding a cell population, comprising the steps of: a) culturing a seeded cell population comprising corneal endothelial cells in the presence of a LATS inhibitor to produce an expanded cell population comprising corneal endothelial cells. Preferably, the LATS inhibitor is a compound according to the present invention having formula A1 or a subformula thereof, or a salt thereof. In another aspect, the present invention relates to a method for expanding a cell population, comprising the steps of: a) culturing a seeded cell population comprising corneal endothelial cells in the presence of a compound having formula A1 or a subformula thereof, or a pharmaceutically acceptable salt thereof, to produce an expanded cell population comprising corneal endothelial cells. Preferably, the compound is selected from formula A2 or a subformula thereof. Also preferably, the salt is a pharmaceutically acceptable salt.Preferably, the compound is selected from the group consisting of: N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propoxy)propan-2-ol; 2,4-dimethyl-4-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)pentan-2-ol; N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclobutyl) Pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-isopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propan-1-ol; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[0041] N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine -amine; 2-(2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propoxy)ethan-1-ol; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; and 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine.

[0042] Also preferably, the compound or its salt is selected from N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine and (S)-N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine.

[0043] In a preferred embodiment of the cell population expansion method, the compound is present at a concentration of 0.5 to 100 micromolar, preferably 0.5 to 25 micromolar, more preferably 1 to 20 micromolar, and particularly preferably about 3 to 10 micromolar. In a preferred embodiment of the cell population expansion method involving limbal stem cells in step a), the compound is present for 12 to 16 days, particularly preferably 14 days. In a preferred embodiment of the cell population expansion method involving corneal endothelial cells in step a), the compound is present for one to two weeks, followed by step b), wherein the cells are cultured in growth medium not supplemented with the compound for a period of time, preferably one to two weeks. In a specific embodiment of the cell population expansion method involving limbal stem cells, the compound according to Formula A1 or its subformulas produces a greater than 30-fold expansion of the inoculum of cells. In another specific embodiment of the cell population expansion method involving limbal stem cells, the compound according to Formula A1 and its subformulas produces a 100-fold to 2200-fold expansion of the inoculum of cells, preferably a 600-fold to 2200-fold expansion. In one embodiment of a method for expanding a cell population involving limbal stem cells, the method according to the present invention produces a cell population having greater than 20% limbal stem cells. In another embodiment of a method for expanding a cell population involving limbal stem cells, the method according to the present invention produces a cell population having greater than 50% limbal stem cells. In another aspect, a method for expanding a cell population involving limbal stem cells according to the present invention produces a cell population having greater than 20% expressing p63α. In another aspect, a method for expanding a cell population involving limbal stem cells according to the present invention produces a cell population having greater than 50% expressing p63α. In a specific embodiment of a method for expanding a cell population involving corneal endothelial cells, the compound according to Formula A1 or its subformulae produces a greater than 10-fold expansion of the inoculum of cells. In another specific embodiment of a method for expanding a cell population involving corneal endothelial cells, the compound according to Formula A1 and its subformulae produces a 15-fold to 600-fold expansion, preferably a 20-fold to 550-fold expansion, of the inoculum of cells. In one embodiment of the present invention, the LATS inhibitor inhibits LATS1 or LATS2, or both LATS1 and LATS2. In a more preferred embodiment, the LATS inhibitor inhibits LATS1 and LATS2. In another preferred embodiment, the cell population expansion method further comprises the use of a gene editing system. Preferably, the method comprises the use of gene editing, wherein the gene editing system specifically targets genes associated with promoting host anti-transplantation immune response. Also preferably, the cells are eye cells or liver cells. In a preferred embodiment, the cells are eye cells. In another preferred embodiment, the cell population expansion method further comprises genetically modifying limbal stem cells, preferably, wherein the genetic modification comprises introducing a gene editing system into the cells, wherein the gene editing system specifically targets genes associated with promoting host anti-transplantation immune response.In another preferred embodiment, the method further comprises genetically modifying corneal endothelial cells, preferably, wherein the genetic modification comprises introducing a gene editing system into the cells, wherein the gene editing system specifically targets genes associated with promoting host anti-transplantation immune responses. In another preferred embodiment, the cell population expansion method further comprises step c) rinsing the expanded cell population to substantially remove the compound according to the present invention.

[0044] In one aspect, the present invention relates to a kit comprising a LATS inhibitor, a growth medium, and instructions for cell population expansion. In another aspect, the present invention relates to a cell population obtainable by a method for cell population expansion according to the present invention. In another aspect, the present invention relates to a cell population obtained by a method for cell population expansion according to the present invention. In another aspect, the present invention relates to an ocular cell population obtainable by a method for cell population expansion according to the present invention. In another aspect, the present invention relates to an ocular cell population obtained by a method for cell population expansion according to the present invention. In one aspect, the present invention relates to a cell population comprising limbal stem cells obtainable by a method for cell population expansion involving limbal stem cells according to the present invention. In another aspect, the present invention relates to a cell population comprising limbal stem cells obtained by a method for cell population expansion involving limbal stem cells according to the present invention. In one aspect, the present invention relates to a cell population comprising corneal endothelial cells obtainable by a method for cell population expansion involving corneal endothelial cells according to the present invention. In another aspect, the present invention relates to a cell population comprising corneal endothelial cells obtained by a method for cell population expansion involving corneal endothelial cells according to the present invention. In another aspect, the present invention relates to an ocular cell delivery formulation comprising a cell population obtainable or obtained by a method for cell population expansion according to the present invention and a composition suitable for ocular delivery as a targeting agent. In a specific embodiment, the targeting agent is GelMa. In another specific embodiment, the positioning agent is fibrin or fibrin glue. Preferably, the cell delivery formulation of limbal stem cells has more than 20% limbal stem cells. Also preferably, the cell delivery formulation of limbal stem cells has more than 20% p63α positive cells. Preferably, the corneal endothelial cells are greater than 500 cells / mm 2 In certain preferred aspects, the cell population obtainable or obtained by the cell population expansion method according to the present invention or the cell delivery formulation according to the present invention has only trace levels of the compound according to the present invention.

[0045] In some aspects of the cell population expansion method, the method further comprises the use of a gene editing system. Preferably, the gene editing system is used to genetically modify cells. In an embodiment of the method according to the present invention, the genetic modification includes reducing or eliminating the expression and / or function of genes associated with promoting host anti-transplantation immune responses. It is also preferred that the gene editing system specifically targets genes associated with promoting host anti-transplantation immune responses. Preferably, the gene editing system is selected from the group consisting of: CRISPR gene editing system, TALEN gene editing system, zinc finger nuclease gene editing system, large range nuclease gene editing system, AAV vector-driven homologous recombination and lentiviral vector-based genome editing technology.

[0046] In one aspect, the present invention relates to an isolated cell population wherein greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the cells are limbal stem cells. Preferably, greater than 20% are limbal stem cells. More preferably, greater than 50% are limbal stem cells. In another preferred embodiment, greater than 70% are limbal stem cells. Particularly preferably, greater than 90% are limbal stem cells. In one embodiment, the cells have been genetically edited.

[0047] In another aspect, the present invention relates to an isolated cell population in which greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the cells express p63α. Preferably, greater than 20% are p63α positive. More preferably, greater than 50% are p63α positive. In another preferred embodiment, greater than 70% are p63α positive. Particularly preferably, greater than 90% are p63α positive. In one embodiment, the cells have been gene-edited.

[0048] In another aspect, the present invention relates to a cell population comprising limbal stem cells, or a cell population according to the present invention, wherein one or more of the cells comprises a non-naturally occurring insertion or deletion of one or more nucleic acid residues of a gene associated with promoting a host anti-transplantation immune response, wherein the insertion and / or deletion results in reduced or abolished expression or function of the gene. In a preferred embodiment, the gene is selected from the group consisting of B2M, HLA-A, HLA-B, and HLA-C. In specific embodiments, the cells have a genetically modified level of B2M expression.

[0049] In another aspect, the present invention relates to a cell population comprising corneal endothelial cells, or a cell population according to the present invention, wherein one or more of the cells comprises a non-naturally occurring insertion or deletion of one or more nucleic acid residues of a gene associated with promoting a host anti-transplantation immune response, wherein the insertion and / or deletion results in reduced or abolished expression or function of the gene. In a preferred embodiment, the gene is selected from the group consisting of B2M, HLA-A, HLA-B, and HLA-C. In specific embodiments, the cells have a genetically modified level of B2M expression.

[0050] In another aspect, the present invention relates to a cell population comprising gene-edited limbal stem cells or corneal endothelial cells. In another aspect, the present invention relates to a cell population comprising gene-edited limbal stem cells. Preferably, the gene editing is performed using CRISPR. Preferably, the B2M gene is also edited.

[0051] In one aspect, the present invention relates to a cell growth promoter comprising a LATS inhibitor. In one embodiment, the present invention relates to an ocular cell growth promoter comprising a LATS inhibitor. In one aspect, the present invention relates to a limbal stem cell growth promoter comprising a LATS inhibitor. Preferably, the LATS inhibitor is a compound having formula A1 or a subformula thereof, or a salt thereof. In another aspect, the present invention relates to a limbal stem cell growth promoter comprising a compound having formula A1 or a subformula thereof, or a salt thereof. In one aspect, the present invention relates to a corneal endothelial cell growth promoter comprising a LATS inhibitor. Preferably, the LATS inhibitor is a compound having formula A1 or a subformula thereof, or a salt thereof. In another aspect, the present invention relates to a corneal endothelial cell growth promoter comprising a compound having formula A1 or a subformula thereof, or a salt thereof.

[0052] In one aspect, the present invention relates to a pharmaceutical composition comprising a compound of formula A2 or its subformulae according to the present invention, or a pharmaceutically acceptable salt or stereoisomer thereof, and at least one pharmaceutically acceptable excipient. Preferably, the composition further comprises a preservation solution or a cryopreservation solution.

[0053] In another aspect, the present invention relates to a cell proliferation medium comprising a LATS inhibitor and a growth medium. Preferably, the LATS inhibitor is a compound according to the present invention having formula A1 or a subformula thereof. In one aspect, the present invention relates to a cell proliferation medium (which comprises a compound according to the present invention having formula A1 or a subformula thereof) and a growth medium. In one embodiment, the cell proliferation medium further comprises cells as provided herein. Preferably, the cell proliferation medium further comprises ocular cells. In another embodiment, the cell proliferation medium further comprises limbal stem cells. Preferably, the limbal stem cells are in suspension. In yet another embodiment, the cell proliferation medium comprises corneal endothelial cells. Preferably, the corneal endothelial cells are in suspension.

[0054] In one aspect, the present invention relates to a cell preparation comprising a LATS inhibitor and cells of a cell population described and / or provided herein. In another aspect, the present invention relates to a cell preparation comprising a LATS inhibitor and ocular cells. In another aspect, the present invention relates to a cell preparation comprising a LATS inhibitor and limbal stem cells. In yet another aspect, the present invention relates to a cell preparation comprising a LATS inhibitor and corneal endothelial cells. Preferably, the LATS inhibitor is a compound of formula A1 or a subformula thereof according to the present invention. In another aspect, the present invention relates to a cell preparation comprising a compound of formula A1 according to the present invention and limbal stem cells. In an alternative aspect, the present invention relates to a cell preparation comprising a compound of formula A1 according to the present invention and corneal endothelial cells. Preferably, the cell preparation further comprises a growth medium. Particularly preferably, the cell preparation further comprises a preservation solution or a cryopreservation solution.

[0055] In another aspect, the present invention relates to an ocular cell delivery formulation comprising a cell preparation according to the present invention and a composition suitable for ocular delivery as a positioning agent. In a specific embodiment, the positioning agent is GelMa. In another specific embodiment, the positioning agent is fibrin or fibrin glue. In another aspect, the present invention relates to an ocular cell delivery formulation comprising a cell preparation according to the present invention and a composition suitable for ocular delivery as a positioning agent. In a specific embodiment, the positioning agent is GelMa. In another specific embodiment, the positioning agent is fibrin or fibrin glue. In certain preferred aspects, the cell preparation according to the present invention has only trace levels of a compound according to the present invention. In yet another specific embodiment, more than 20% of the cells in the cell delivery formulation are limbal stem cells.

[0056] In another specific embodiment, greater than 20% of the cells in the cell delivery formulation are p63α expressing cells.

[0057] In yet another aspect, the present invention relates to an ocular cell delivery formulation comprising a cell formulation according to the present invention and a composition suitable for ocular delivery as a positioning agent. In a specific embodiment, the positioning agent is GelMa. Preferably, the corneal endothelial cells are in suspension. In an alternative embodiment, the corneal endothelial cells are present at a density of greater than 500 cells / mm 2 The corneal endothelial cells are present in the cell delivery formulation at a density of 1000 to 3500 cells / mm. 2 (area), more preferably 2000 to about 3000 cells / mm 2 In certain preferred aspects, the cell preparations according to the invention have only trace levels of the compound according to the invention.

[0058] Preferably, the growth medium in the method or cell preparation according to the present invention is selected from the group consisting of: Dulbecco's modified Eagle's medium (DMEM) supplemented with fetal bovine serum (FBS), human endothelial serum (SF) medium with human serum, X-VIVO15 medium and DMEM / F12 optionally supplemented with calcium chloride; preferably X-VIVO15 medium.

[0059] Preferably, the preservation solution or cryopreservation solution according to the invention comprises Optisol or PBS (phosphate buffered saline) solution, and the cryopreservation solution additionally comprises glycerol, dimethyl sulfoxide, propylene glycol or acetamide.

[0060] In another aspect, the present invention relates to a kit comprising a composition suitable for ocular delivery and a LATS inhibitor. Preferably, the LATS inhibitor is a compound according to the present invention having Formula A2 or a subformula thereof. In another aspect, the present invention relates to a kit comprising a composition suitable for ocular delivery and a compound according to the present invention having Formula A2 or a subformula thereof. Preferably, the kit comprises instructions for use. In one embodiment, the composition suitable for ocular delivery is a localizing agent or a topical eye drop. Preferably, the composition suitable for ocular delivery is a localizing agent. In a specific embodiment, the kit further comprises limbal stem cells. In another specific embodiment of the kit, the composition suitable for ocular delivery is a localizing agent that is GelMa. In an alternative specific embodiment of the kit, the composition suitable for ocular delivery is a localizing agent that is fibrin or fibrin glue. In yet another specific embodiment, greater than 20% of the cells in the kit are limbal stem cells. In another specific embodiment, greater than 20% of the cells in the kit are cells expressing p63α. In an alternative specific embodiment, the kit comprises corneal endothelial cells. In another specific embodiment, the composition suitable for ocular delivery of corneal endothelial cells is a localizing agent that is GelMa. In yet another specific embodiment, the corneal endothelial cells are present as a monolayer. Preferably, the corneal endothelial cells are present at a density of greater than 500 cells / mm 2 Particularly preferably, the corneal endothelial cells are present at a density of 1000 to 3500 cells / mm 2 (area), more preferably 2000 to about 3000 cells / mm 2 The density of (area) exists.

[0061] In a preferred embodiment according to the present invention, the composition suitable for eye delivery is a positioning agent, which is a biomatrix. Preferably, the composition suitable for eye delivery according to the present invention is a positioning agent selected from the group consisting of: fibrin, collagen, gelatin, cellulose, amniotic membrane, fibrin glue, polyethylene (ethylene glycol) diacrylate (PEGDA), GelMA, comprising the following positioning agent: polymer, cross-linked polymer or comprising one or more of the following hydrogels: hyaluronic acid, polyethylene glycol, polypropylene glycol, polyethylene oxide, polypropylene oxide, poloxamer, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinyl pyrrolidone, poly (lactide-to-glycolide), alginate, gelatin, collagen, fibrinogen, cellulose, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl guar gum, gellan gum, guar gum, xanthan gum and carboxymethyl cellulose and derivatives thereof, copolymers thereof, and combinations thereof. In a preferred embodiment according to the present invention, the composition suitable for eye delivery is a positioning agent, which is GelMa, fibrin or fibrin glue. In a specific embodiment according to the present invention, the composition suitable for eye delivery is a positioning agent, which is GelMa. In other specific embodiments according to the present invention, the composition suitable for eye delivery is a positioning agent, which is fibrin or fibrin glue. Preferably, the positioning agent is fibrin glue. Fibrin glue is known in the art, including, for example, TISSEEL VH fibrin sealant (Baxter AG, Vienna, Austria) (Panda et al., 2009, Indian J Ophthalmol. [Indian Journal of Ophthalmology] September-October; 57 (5): 371-379). In one embodiment, fibrin glue is used to deliver limbal stem cells. In another embodiment, GelMa is used to deliver corneal endothelial cells.

[0062] In more preferred embodiments according to the present invention, wherein limbal stem cells are present in combination with a targeting agent, greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the cells are limbal stem cells. Preferably, greater than 20% are limbal stem cells. More preferably, greater than 50% are limbal stem cells. In another preferred embodiment, greater than 70% are limbal stem cells. Particularly preferably, greater than 90% are limbal stem cells.

[0063] In another preferred embodiment according to the present invention, wherein the cells are present in combination with a localizing agent, more than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the cells express p63α. Preferably, more than 20% of the cells are p63α-positive. More preferably, more than 50% of the cells are p63α-positive. In another preferred embodiment, more than 70% of the cells are p63α-positive. Particularly preferably, more than 90% of the cells are p63α-positive.

[0064] In a more preferred embodiment according to the present invention, the corneal endothelial cells are present in combination with a positioning agent. Preferably, the corneal endothelial cells are in a single layer. More preferably, the corneal endothelial cells are present at a density of greater than 500 cells / mm 2 Particularly preferably, the corneal endothelial cells are present at a density of 1000 to 3500 cells / mm 2 (area), more particularly preferably 2000 to about 3000 cells / mm 2 The density of (area) exists.

[0065] In a further particularly preferred embodiment of the present invention, the LATS inhibitor inhibits LATS1 or LATS2, or LATS1 and LATS2. In a more particularly preferred embodiment according to the present invention, the LATS inhibitor inhibits LATS1 and LATS2.

[0066] In a preferred embodiment according to the present invention, the compound is selected from the group consisting of: 2-methyl-1-(2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propoxy)propan-2-ol; N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; (S)-N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propoxy)propan-2-ol; ,4-dimethyl-4-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)pentan-2-ol; N-isopropyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclobutyl)pyrido[3,4-d]pyrimidin-4-amine; N-isopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6- naphthyridin-1-amine; 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propan-1-ol; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2- [3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; 2-(2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propoxy)ethan-1-ol; and (R)-N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine.

[0067] Also preferably, the compound or its salt is selected from N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine and (S)-N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine. Preferably, the compound or its salt is N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine.

[0068] In particularly preferred embodiments according to the present invention, the compounds according to the invention are present in a concentration of 0.5 to 100 micromolar, preferably 0.5 to 25 micromolar, more preferably 1 to 20 micromolar, particularly preferably about 3 to 10 micromolar.

[0069] In one aspect, the present invention relates to a method of transplanting a cell population into a subject, the method comprising administering a cell population obtainable or obtained by the cell population expansion method or the method of culturing cells or the LATS inhibition method according to the present invention.

[0070] The present invention also relates to a method for transplanting an ocular cell population into the eye of a subject, the method comprising administering a cell population obtainable or obtained by a cell population expansion method, a cell culture method, or a LATS inhibition method according to the present invention, wherein the cells are ocular cells. The ocular cells are preferably limbal stem cells or corneal endothelial cells. In another aspect, the present invention relates to a method for transplanting an ocular cell population into the cornea of ​​a subject, the method comprising administering a cell delivery formulation according to the present invention.

[0071] In another aspect, the present invention relates to a method for transplanting a cell population comprising limbal stem cells onto the cornea of ​​a subject, the method comprising administering a cell population comprising limbal stem cells obtainable or obtained by a cell population expansion method or a cell culturing method or a LATS inhibition method according to the present invention. In another aspect, the present invention relates to a method for transplanting a cell population comprising limbal stem cells onto the cornea of ​​a subject, the method comprising administering a cell delivery formulation according to the present invention.

[0072] On the other hand, the present invention provides a method for transplanting a cell population comprising limbal stem cells onto the cornea of ​​a subject, the method comprising amplifying the cell population by culturing the cell population comprising limbal stem cells with a cell proliferation medium comprising a LATS inhibitor according to the present invention, preferably rinsing the amplified cell population to substantially remove the LATS inhibitor, and administering the cells to the cornea of ​​the subject. Preferably, prior to the administration, the cell population is combined with a biomatrix. In a specific embodiment, prior to the administration, the cell population is combined with a biomatrix as GelMA. In another specific embodiment, prior to the administration, the cell population is combined with fibrin glue. In one embodiment, the cell population is combined with a carrier as a contact lens. In a specific embodiment, the cell population comprising limbal stem cells is combined with a biomatrix as GelMA, and the GelMA is polymerized on a carrier as a contact lens. In another specific embodiment, the cell population comprising limbal stem cells is combined with fibrin glue and a contact lens.

[0073] In one aspect, the present invention relates to a method for transplanting a corneal endothelial cell population onto the cornea of ​​a subject, the method comprising administering a corneal endothelial cell population obtainable or obtained by a cell population expansion method or a cell culturing method or a LATS inhibition method according to the present invention. In another aspect, the present invention relates to a method for transplanting a corneal endothelial cell population onto the cornea of ​​a subject, the method comprising administering a cell delivery formulation according to the present invention.

[0074] On the other hand, the present invention relates to a method for transplanting a cell population comprising corneal endothelial cells onto the cornea of ​​a subject, the method comprising amplifying the cell population by culturing the cell population comprising corneal endothelial cells with a cell proliferation medium comprising a LATS inhibitor according to the present invention, rinsing the amplified cell population to substantially remove the LATS inhibitor, and administering the cells to the cornea of ​​the subject. Preferably, prior to the administration, the cells are combined with a biomatrix. In a specific embodiment, prior to the administration, the cells are combined with a biomatrix that is GelMA. In a more specific embodiment, the corneal endothelial cells are combined with a biomatrix that is bioprinted on the surface of the eye. Particularly preferably, the corneal endothelial cells are combined with a biomatrix that is GelMA and bioprinted on the surface of the eye by polymerizing the GelMA via a light-triggered reaction.

[0075] On the other hand, the present invention relates to a method for transplanting a cell population into the eye of a subject, the method comprising combining cells with a biomatrix to form a cell / biomatrix mixture, injecting the mixture into the eye of the subject or applying the mixture to the surface of the subject's eye, and guiding and fixing the cells (e.g., on the cornea) by using a light source such as ultraviolet A or a white light source by cell bioprinting in or on the eye. In certain embodiments, the light source produces light with a wavelength of at least 350nm. In certain embodiments, the light source produces light within the range of 350nm to 420nm. For example, an LED light source can be used to produce light with a wavelength of 365nm or 405nm or any other wavelength above 350nm, or a mercury lamp with a bandpass filter can be used to produce light with a wavelength of 350nm to 700nm, such as light with a wavelength of 365nm or 405nm. In another embodiment, the light source produces visible white light, and the white light has a wavelength, for example, within the range of 400nm to 700nm. In certain embodiments, the cell is an eye cell, such as a corneal cell, such as a corneal endothelial cell.

[0076] In another aspect, the present invention relates to a method of transplanting a population of corneal endothelial cells into an eye of a subject, the method comprising culturing the population of corneal endothelial cells in a cell proliferation medium comprising a LATS inhibitor, combining the corneal endothelial cells with a biomatrix to form a cell / biomatrix mixture, injecting the mixture into the subject's eye, and bioprinting the cells in the eye by directing and fixing the cells on the cornea using a light source (e.g., UVA or LED or visible light source).

[0077] In another aspect, the present invention relates to a method for preventing or treating an eye disease or disorder using a LATS inhibitor. Preferably, the LATS inhibitor is a compound according to the present invention having formula A1 or a subformula thereof. In yet another aspect, the present invention relates to a method for preventing or treating an eye disease or disorder using a compound according to the present invention having formula A2 or a subformula thereof. In a preferred embodiment, the method for preventing or treating an eye disease or disorder further comprises a method for inhibiting LATS in a cell population or a method for expanding a cell population according to the present invention, wherein the cells are ocular cells. Preferably, the method for preventing or treating an eye disease or disorder comprises administering to a subject in need thereof a therapeutically effective amount of a cell population obtainable or obtained by a method for expanding a cell population according to the present invention, wherein the cells are ocular cells. In another preferred embodiment, the method for preventing or treating an eye disease or disorder comprises administering to a subject in need thereof a therapeutically effective amount of a cell delivery formulation according to the present invention, wherein the cells are ocular cells. In yet another preferred embodiment, the method for preventing or treating an eye disease or disorder comprises the step of a method according to the present invention for transplanting a cell population comprising ocular cells into the eye of a subject. The ocular cells are preferably limbal stem cells or corneal endothelial cells. In yet another preferred embodiment, the method for preventing or treating an eye disease or disorder comprises the steps of a method according to the present invention for transplanting a cell population comprising limbal stem cells onto the cornea of ​​a subject. In an alternative preferred embodiment, the method for preventing or treating an eye disease or disorder comprises the steps of a method according to the present invention for transplanting a corneal endothelial cell population onto the cornea of ​​a subject. In a specific embodiment of the method for preventing or treating an eye disease or disorder according to the present invention, the cell population obtainable or obtained by the cell population expansion method according to the present invention or the cell delivery formulation according to the present invention is used simultaneously or sequentially with one or more drugs selected from the group consisting of dexamethasone, cyclosporine, tobramycin and cefazolin.

[0078] In one aspect, the present invention relates to a YAP (yes associated protein) modulator for use in a method of transplanting a cell population into a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a cell population obtainable or obtained according to a cell population expansion method of the present invention or a cell delivery formulation according to the present invention. Preferably, the YAP modulator is a LATS inhibitor. Preferably, the cells are ocular cells.

[0079] In one aspect, the present invention relates to a YAP (yes associated protein) modulator for use in a method of transplanting a cell population comprising limbal stem cells onto the cornea of ​​a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a cell population obtainable or obtained by a cell population expansion method according to the present invention or a cell delivery formulation according to the present invention. Preferably, the YAP modulator is a LATS inhibitor.

[0080] In another aspect, the present invention relates to a YAP modulator for use in a method for treating limbal stem cell deficiency, the method comprising administering to a subject in need thereof a therapeutically effective amount of a cell population obtainable or obtained by the cell population expansion method of the present invention or a cell delivery formulation of the present invention. Preferably, the YAP modulator is a LATS inhibitor.

[0081] In one aspect, the present invention relates to a YAP (yes associated protein) modulator for use in a method of transplanting a corneal endothelial cell population onto the cornea of ​​a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a cell population obtainable or obtained by a cell population expansion method according to the present invention or a cell delivery formulation according to the present invention. Preferably, the YAP modulator is a LATS inhibitor.

[0082] In another aspect, the present invention relates to a YAP modulator for use in a method for treating corneal endothelial dysfunction, the method comprising administering to a subject in need thereof a therapeutically effective amount of a cell population obtainable or obtained by the cell population expansion method of the present invention or a cell delivery formulation of the present invention. Preferably, the YAP modulator is a LATS inhibitor.

[0083] In yet another embodiment, the present invention relates to a method of treating a disease or disorder, comprising administering to a subject in need thereof a cell population, wherein the population has been grown in the presence of an agent capable of inhibiting the activity of LATS1 and LATS2 kinases; thereby inducing YAP translocation and driving downstream gene expression to promote cell proliferation. In another embodiment, the agent is a compound of formula A1 or a subformula thereof, or a pharmaceutically acceptable salt thereof. Preferably, the cell is an ocular cell.

[0084] In one aspect, the present invention relates to a compound according to formula A2 or a subformula thereof according to the present invention, or a pharmaceutically acceptable salt thereof, for use in therapy or as a medicament. Preferably, the compound is for use in an eye disease or disorder.

[0085] In another aspect, the present invention relates to a LATS inhibitor for use in eye diseases or disorders, preferably wherein the LATS inhibitor is a compound. Preferably, the compound is a compound according to the present invention having formula A1 or a subformula thereof, or a pharmaceutically acceptable salt thereof.

[0086] In yet another aspect, the present invention relates to the use of a compound of formula A2 or its subformulae according to the present invention, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament. In another aspect, the present invention relates to the use of a compound of formula A1 or its subformulae according to the present invention, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating an eye disease or disorder.

[0087] In a preferred embodiment of the compound used according to the invention or the LATS inhibitor used according to the invention or the use of the compound for the preparation of a medicament according to the invention, the use also comprises a method for inhibiting LATS in a cell population or a method for expanding a cell population according to the invention.

[0088] In another preferred embodiment of the use of a compound for use according to the present invention, or a LATS inhibitor for use according to the present invention, or a compound for use in the preparation of a medicament according to the present invention, the use comprises administering to a subject in need thereof a therapeutically effective amount of a cell population obtainable or obtained by the method for cell population expansion according to the present invention. In yet another preferred embodiment of the use of a compound for use according to the present invention, or a LATS inhibitor for use according to the present invention, or a compound for use in the preparation of a medicament according to the present invention, the use comprises administering to a subject in need thereof a therapeutically effective amount of a cell delivery formulation according to the present invention. In a preferred embodiment of the use of a compound for use according to the present invention, or a LATS inhibitor for use according to the present invention, or a compound for use in the preparation of a medicament according to the present invention, the use comprises the step of a method according to the present invention for transplanting a cell population comprising ocular cells onto the cornea of ​​a subject. In an even more preferred embodiment of the use of a compound for use according to the present invention, or a LATS inhibitor for use according to the present invention, or a compound for use in the preparation of a medicament according to the present invention, the use comprises the step of a method according to the present invention for transplanting a cell population comprising limbal stem cells onto the cornea of ​​a subject. In an even more preferred embodiment of the use of a compound for use according to the present invention, or a LATS inhibitor for use according to the present invention, or a compound for use in the preparation of a medicament according to the present invention, the use comprises the step of a method according to the present invention for transplanting a cell population comprising corneal endothelial cells onto the cornea of ​​a subject. In a specific embodiment of the use of the compound used according to the present invention or the LATS inhibitor used according to the present invention or the compound in the preparation of a medicament according to the present invention, the cell population obtainable or obtained by the cell population expansion method according to the present invention or the cell delivery formulation according to the present invention is used simultaneously or sequentially with one or more drugs selected from the group consisting of dexamethasone, cyclosporine, tobramycin and cefazolin.

[0089] In a preferred embodiment according to the present invention, the eye disease or disorder is associated with a limbal stem cell deficiency. In a more preferred embodiment, the eye disease or disorder is a limbal stem cell deficiency. More preferably, the eye disease or disorder is: limbal stem cell deficiency caused by an injury or disorder selected from the group consisting of: chemical burns, thermal burns, radiation damage, aniridia, sclerokeratosis, multiple endocrine neoplasia, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, collagen vascular disease, chronic non-autoimmune inflammatory disorders caused by contact lens use, dry eye, rosacea, staphylococcal limbus, keratitis (including bacterial, fungal and viral keratitis), pterygium or tumor, limbal stem cell deficiency caused by multiple eye surgeries, pterygium or tumor resection or cryotherapy; and limbal stem cell deficiency caused by drug toxicity caused by drugs selected from the group consisting of: preservatives (thimerosal, benzalkonium), local anesthetics, pilocarpine, beta-blockers, mitomycin, 5-fluorouracil, silver nitrate and oral drugs that cause Stevens-Johnson syndrome. Particularly preferably, the ocular disease or disorder is a limbal stem cell deficiency caused by an injury or disorder selected from the group consisting of chemical burns, aniridia, Stevens Johnson syndrome and contact lens use.

[0090] In a preferred embodiment according to the present invention, the eye disease or disorder is associated with a decrease in corneal endothelial cell density. In a more preferred embodiment, the eye disease or disorder is corneal endothelial dysfunction. More preferably, the eye disease or disorder is corneal endothelial dysfunction, which is selected from the group consisting of: Fuchs corneal endothelial dystrophy, bullous keratopathy (including pseudophakic bullous keratopathy and aphakic bullous keratopathy), corneal transplant failure, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked endothelial corneal dystrophy, aniridia and corneal endotheliitis. In a specific embodiment, the eye disease or disorder is selected from the group consisting of: Fuchs corneal endothelial dystrophy, bullous keratopathy (including pseudophakic bullous keratopathy and aphakic bullous keratopathy) and corneal transplant failure.

[0091] The present invention further relates to a method for promoting wound healing, in particular for treating or ameliorating the symptoms of burns, acute and chronic skin ulcers, comprising administering an effective amount of a LATS inhibitor to a subject in need thereof.

[0092] In certain other aspects, the present invention relates to a method of promoting wound healing, comprising administering a therapeutically effective amount of a compound of Formula A1 or its subformulae, or a pharmaceutically acceptable salt or stereoisomer thereof.

[0093] In another aspect, the present invention relates to compounds and compositions useful for promoting wound healing. In another aspect, the present invention relates to compounds and compositions useful for the preparation of a medicament for promoting wound healing.

[0094] The present invention also relates to a method for promoting wound healing, in particular a method for treating or ameliorating the symptoms of burns, acute skin ulcers and chronic skin ulcers, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having formula A1 or a subformula thereof and optionally a second therapeutic agent, which is another compound of the present invention or another type of therapeutic agent.

[0095] The present invention also relates to a method for promoting ocular wound healing, comprising administering a therapeutically effective amount of a compound of the present invention to the eye of a subject. In one embodiment, the ocular wound is a corneal wound. In other embodiments, the ocular wound is an injury or surgical wound.

[0096] In another aspect, the present invention relates to compounds and compositions useful for liver regeneration and re-growth. In certain other aspects, the present invention relates to a method for promoting liver regeneration and re-growth, comprising administering a therapeutically effective amount of a compound of Formula A1 or a subformula thereof, or a pharmaceutically acceptable salt or stereoisomer thereof. In another aspect, the present invention relates to compounds and compositions useful for preparing a medicament for promoting liver regeneration and re-growth.

[0097] The present invention also relates to methods for: liver regeneration and liver regrowth, in particular for treating insufficient liver regrowth after marginal graft transplantation; for supporting enhanced regrowth of the remaining liver mass after extensive hepatectomy; for regeneration of the liver in patients following acute liver failure caused by viral hepatitis, drug-induced liver injury, autoimmune hepatitis, ischemic and congestive liver disease; for treating patients with chronic liver injury and underlying liver fibrosis caused by non-alcoholic steatohepatitis, alcoholic steatohepatitis, chronic viral hepatitis B and C, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease and drug-induced liver fibrosis to enhance regenerative capacity and accelerate fibrosis regression, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to the present invention and, optionally, a second therapeutic agent, which is another compound of the present invention or one other type of therapeutic agent.

[0098] In certain embodiments, the present invention relates to a method for producing a cell material for cell therapy and / or transplantation, the method comprising ex vivo administration of a compound of Formula A1 or its subformulae, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. The cell material may comprise eye, liver, or skin cells.

[0099] Furthermore, in certain embodiments, the present invention relates to a method for promoting liver regeneration and liver re-growth, comprising ex vivo administration of a compound of Formula A1 or its subformulae, or a pharmaceutically acceptable salt or stereoisomer thereof.

[0100] The present invention also relates to an ex vivo method for expanding a hepatocyte population, said method comprising using a compound of the present invention or a pharmaceutically acceptable salt or stereoisomer thereof.

[0101] Other features and advantages of the invention will be apparent from the following detailed description and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0102] Figure 1 : As shown by Western blot, LATS inhibitors (Compounds Example 49 and Example 133) induced YAP dephosphorylation in LSCs within 1 hour of treatment.

[0103] Figure 2: Immunolabeling of p63-alpha in limbal stem cell cultures demonstrates that the LSC population can be expanded when maintained in culture medium containing LATS inhibitors (Compounds Example 49 and Example 133). Figure 2A In the presence of growth medium and DMSO, only a few detached cells adhered to the dish and remained viable for up to 6 days. Most cells expressed human nuclear markers, but few expressed p63α. Figure 2B and 2C In contrast, cells formed colonies and expressed p63α in the presence of LATS inhibitor compounds Example No. 49 and Example No. 133. These results indicate that LATS inhibitors promote the expansion of a cell population with a p63α-positive phenotype. Figure 2D : The cells were passaged and cultured in the presence of LATS inhibitor compound Example No. 49 for two weeks to allow the cell population to expand and form a confluent culture expressing p63α.

[0104] Figure 3 : siRNA knockdown of LATS1 and LATS2 activated LSC proliferation in culture, as indicated by the percentage of EdU-positive cells.

[0105] Figure 4Immunolabeling of LSC markers δN-p63α / β / γ, ABCG2, and C / EBPδ showed that LSCs maintained in culture medium containing LATS inhibitors (Compound Example 49 and Example 133) expressed typical LSC markers. The results indicate that cells cultured in DMSO do not typically express markers normally expressed by LSCs, such as δN-p63α / β / γ, ABCG2, and C / EBPδ. In contrast, cells cultured in the presence of LATS inhibitors expressed markers normally expressed by LSCs, such as δN-p63α / β / γ, ABCG2, and C / EBPδ.

[0106] Figure 5: Immunolabeling of undifferentiated LSC marker p63α and corneal epithelial cell marker keratin 12 showed that the LATS inhibitor ( Figure 5A : Compound Example 49, Figure 5B : Compound Example 47, Figure 5C : Compound Example 12, Figure 5D : Compound Example 261) culture-expanded LSC populations can differentiate into corneal epithelial cells when transferred to conditions that enable differentiation. Shown is a view of the transition from p63α-positive cell identity to keratin 12 identity.

[0107] Figure 6 : LSCs were labeled with fluorescent proteins to confirm that LSCs attached to contact lenses using GelMA polymerization can be delivered to the rabbit ocular surface ex vivo. Arrows indicate the attachment sites of LSCs.

[0108] Figure 7: Figure 7A : Transplanted eye, keratin 12 staining; Figure 7B : Transplanted eye, keratin 19 staining; Figure 7C : Non-transplanted control eyes, keratin 12 staining; Figure 7D : Non-transplanted control eye, keratin 19 staining. These figures show that in a rabbit limbal stem cell deficiency model, LSC populations expanded in a culture medium containing compound Example No. 12 were combined with GelMA and delivered to the rabbit corneal surface in vivo via a contact lens, which resulted in the regeneration of keratin 12-positive corneal epithelium ( Figure 7A ) and prevented conjunctivalization of keratin 19-positive conjunctival cells in transplanted eyes. Figure 7B : Arrows indicate the absence of keratin 19 staining. In contrast, non-transplanted rabbit eyes showed the absence of keratin 12-positive corneal epithelial repair. Figure 7C : Arrows indicate the absence of keratin 12 staining. In contrast, signs of conjunctivalization were observed, as indicated by the presence of keratin 19 staining. Figure 7D : Arrows indicate positive keratin 19 staining areas.

[0109] Figure 8: Figure 8A: Rabbit eyes transplanted with human LSCs; Figure 8B : Control rabbit eyes, not transplanted with human LSCs. These figures show that the cells that restored the corneal epithelium of the transplanted eyes were human, as evidenced by the presence of human mitochondrial proteins (arrows indicate the presence of human mitochondrial markers). Figure 8A In contrast, the ocular surface of the non-transplanted eye showed no staining for human mitochondrial proteins ( Figure 8B : absence of human mitochondrial markers).

[0110] Figure 9 : Microscopic images of LSCs delivered via TISSEEL to collagen-coated 24-well plates show that the cell population recovers to cover the culture surface within 2 weeks.

[0111] Figure 10 : CellTracker Green CMFDA-labeled LSCs were delivered to the human cornea ex vivo and covered with a protective contact lens.

[0112] Figure 11 : HEK-293 cells labeled with red and green dyes were bioprinted on top of isolated rabbit corneas in a yin-yang pattern (shown as dark gray and light gray patterns).

[0113] Figure 12 : Reduced immune rejection by CRISPR / Cas9-mediated deletion of the β-2-microglobulin (B2M) gene in LSCs: FACS analysis showed CRISPR-mediated B2M deletion and subsequent elimination of HLA A, HLA B, and HLA C in 21% of LSCs.

[0114] Figure 13 : A population of B2M negative / HLA A, HLA B, HLA C negative LSCs was expanded using compound Example No. 48a to produce a cell preparation in which 97% of the cells did not express HLA A, HLA B, HLA C.

[0115] Figure 14 : LATS inhibitors (Compound Example 133 and Example 49) induce YAP translocation into the nucleus of corneal endothelial cells (CECs).

[0116] Figure 15: LATS inhibitors (Compound Example 133 and Example 49) induce YAP dephosphorylation in CECs within 1 hour of treatment. As shown below: Figure 15a by Western blot; Figure 15b: a graph showing phosphorylated YAP levels normalized to β-actin; Figure 15c: a graph showing phosphorylated YAP levels normalized to total YAP.

[0117] Figure 16Figure 3: CECs grown in the presence or absence of a LATS inhibitor. The Incucyte system (Essen Biosciences) was used to measure CEC confluence by real-time quantitative live cell analysis over a time course. Compounds Example 49 (black squares) and Example 133 (light gray squares) induced robust CEC proliferation; whereas CECs in the vehicle (DMSO, dark gray squares) exhibited minimal proliferation.

[0118] Figure 17 : siRNA knockdown of LATS1 and LATS2 activates corneal endothelial cell proliferation in culture, as shown by the percentage of EdU-positive cells.

[0119] Figure 18: Zonula occludens-1 (ZO-1) immunolabeling shows that CECs proliferate in the presence of LATS inhibitor compound Example 49 (Figure 18b), form tight junctions, endothelial structures, and retain normal cell size and morphology characteristics of functional CECs. CECs proliferated in the presence of vehicle (DMSO) alone exhibit polymegatism characteristics of dysfunctional CECs (Figure 18a).

[0120] Figure 19 Quantitative RT-PCR analysis showed that corneal endothelial cells expanded with LATS inhibitor compound Example 49 expressed genes normally expressed by corneal endothelial cells in vivo, including collagen 8a2, AQP1, and SLc4A11. These cells did not express markers of other epithelial cells present in the eye, including RPE65 (a marker of retinal pigment epithelium) and CD31 (a marker of vascular epithelium).

[0121] Figure 20: Immunohistochemical analysis shows that corneal endothelial cells expanded with LATS inhibitor compound Example 49 express genes normally expressed by corneal endothelial cells in vivo, including Na / K ATPase (Figure 20a) and collagen 8a2 (Figure 20b).

[0122] Figure 21: FACS analysis of corneal endothelial cell populations expanded in the presence of LATS inhibitor compound Example 47 and CECs cultured in the absence of LATS inhibitors. Cell populations expanded in the presence of LATS inhibitors expressed low levels of CD73 (Figure 21a, gray line), CD44 (Figure 21b, gray line), CD166 (Figure 21c, gray line), and CD105 (Figure 21d, gray line); whereas cell populations cultured in the absence of LATS inhibitors expressed high levels of CD44, CD73, CD105, and CD166 (black line).

[0123] Figure 22: Bubble suppression method, which describes Method 1, further described under the "Bioprinting Section," wherein a biomatrix is ​​applied to the eye to deliver a cell formulation according to the present invention. Figure 22a. Injection of a large dose of biomatrix; Figure 22b. Injection of bubbles beneath the biomatrix to diffuse across the cornea; Figure 22c. Curing the biomatrix using a UV or blue light source; Figure 22d. Removal of bubbles and replacement with a balanced salt solution.

[0124] Figure 23: Subtractive method using femtosecond (FS) laser, which describes Method 2, further described under "Bioprinting Section," wherein a biomatrix is ​​applied to the eye to deliver a cell formulation according to the present invention. Figure 23a: Destruction of dysfunctional endothelium using FS; Figure 23b: Injection of biomatrix into the anterior chamber; Figure 23c: Curing of biomatrix using UV or blue light; Figure 23d: Detachment of unwanted biomatrix using FS; Figure 23e: Removal of detached biomatrix using tweezers.

[0125] FIG24 : Dye mask method, which describes method 3 further described under the “Bioprinting section”, wherein a biomatrix is ​​applied to the eye to deliver a cell preparation according to the present invention. FIG24 a stains the endothelium with a dye (e.g., trypan blue); FIG24 b strips the dysfunctional endothelium; FIG24 c injects the stained biomatrix; FIG24 d cures the biomatrix with a UV or blue light source; FIG24 e rinses the uncured biomatrix.

[0126] Figure 25: Dye dispense method, which describes Method 4, further described under the "Bioprinting Section," wherein a biomatrix is ​​applied to the eye to deliver a cell formulation according to the present invention. Figure 25a: Draining the anterior chamber; Figure 25b: Using a soft tip / brush cannula to dispense biomatrix to the posterior cornea; Figure 25c: Using a UV or blue light source to cure the biomatrix; Figure 25d: Filling the eye with a balanced salt solution.

[0127] Figure 26 A bioprinting apparatus as further described in Example C11 is schematically shown.

[0128] Figure 27 The results showed that cells could be bioprinted on the back of the cornea using a handheld device that projected 365nm UVA light through the cornea. After rinsing away the unpolymerized and unattached material, a circular pattern of fluorescent protein-labeled cells remained on the back of the cornea.

[0129] Figure 28 In a rabbit model of corneal endothelial dystrophy, CECs bioprinted on the posterior cornea can reconstruct the corneal endothelium. The results showed that in experimental rabbits, the corneal endothelial structure can be detected using ZO-1 immunohistochemistry ( Figure 28AIn the right eye of a rabbit in which the corneal endothelium was surgically removed and no CECs were bioprinted, there was no ZO-1 staining, indicating the absence of normal corneal endothelial structure ( Figure 28B In the right eye of a rabbit in which the corneal endothelium was surgically removed and CEC printing was performed, ZO-1 staining was present, indicating that the corneal endothelial structure had been reconstructed ( Figure 28C ). Figure 28D and Figure 28E The results show that human nuclear antigen immunostaining was absent in eyes that did not receive any human CECs. In contrast, human nuclear antigen-positive cells covered the imaged area in eyes where human CECs were bioprinted ( Figure 28F ), which indicates that Figure 28C The ZO-1 labeled corneal endothelial construct shown is composed of human CECs bioprinted on the posterior side of a rabbit cornea.

[0130] Figure 29 : Red fluorescent protein-labeled HEK-293 cells were bioprinted into structures with different letters on the posterior side of an ex vivo human cornea.

[0131] Figure 30 : Vector diagram showing the design of AAV2 vectors used to express CRISPR systems in LSCs and CECs. ( Figure 30 Disclosure SEQ ID NO:f28).

[0132] Figure 31 : FACS analysis of the expression of the AAV-mediated CRISPR system that enables deletion of B2M and subsequent elimination of HLA A, HLAB, and HLA C in LSCs.

[0133] Figure 32 : FACS analysis of the AAV-mediated CRISPR system that enables deletion of B2M and subsequent elimination of HLA A, HLAB, and HLA C expression in CECs.

[0134] Figure 33A : Figure 33A Western blot of pYAP in lysates of human HaCaT cells that were untreated or treated with 40 pM siRNA against MST1 / 2 or LATS1 / 2, respectively; actin was used as a control.

[0135] Figure 33B : Figure 33B is a Western blot of pYAP in lysates of human HaCaT cells that were untreated or treated with 9 μM Example 133; actin was used as a control.

[0136] Figure 33C : Figure 33C The relative inhibitory activity against LATS1 is about 10-4 Graph of Example 133 concentrations ranging from μM to 1 μM. Calculated IC of Example 133 against LATS1 50 is 1.3nM.

[0137] Figure 34 : is a bar graph of relative Cyr61 / Gapdh expression levels compared to Example 133 concentrations of 0, 0.2 mg / mL and 2 mg / mL.

[0138] Figure 35A : Figure 35A Micrographs of mouse skin topically treated with vehicle or Example 133 are shown.

[0139] Figure 35B : Figure 35B is a scatter plot comparing the percentage of Ki67+ cells in the skin of mice treated with vehicle or Example 133. DETAILED DESCRIPTION

[0140] LATS

[0141] LATS is an abbreviation for large tumor suppressor kinase. As used herein, LATS refers to LATS1 and / or LATS2. As used herein, LATS1 refers to large tumor suppressor kinase 1, and LATS2 refers to large tumor suppressor kinase 2. Both LATS1 and LATS2 have serine / threonine protein kinase activity. LATS1 and LATS2 have been assigned the Human Genome Organization (HUGO) Gene Nomenclature Committee identifiers: HGNC ID 6514 and HGNC ID 6515, respectively. LATS1 is sometimes also referred to as WARTS or wts in the art, and LATS2 is sometimes also referred to as KPM in the art. Representative LATS sequences include, but are not limited to, protein sequences available from the National Center for Biotechnology Information protein database as shown below: NP_004681.1 (LATS1), NP_001257448.1 (LATS1), and NP_055387.2 (LATS2).

[0142] LATS1: NP_004681.1 (serine / threonine-protein kinase LATS1 isoform 1, Homo sapiens) (SEQ ID NO: 1)

[0143] 1 mkrsekpegy rqmrpktfpa snytvssrqm lqeireslrn lskpsdaaka ehnmskmste

[0144] 61 dprqvrnppk fgthhkalqe irnsllpfan etnssrstse vnpqmlqdlq aagfdedmvi

[0145] 121 qalqktnnrs ieaaiefisk msyqdprreq maaaaarpin asmkpgnvqqsvnrkqswkg

[0146] 181 skeslvpqrh gpplgesvay hsespnsqtd vgrplsgsgi safvqahpsngqrvnppppp

[0147] 241 qvrsvtpppp prgqtppprg ttppppswep nsqtkrysgn meyvisrispvppgawqegy

[0148] 301 pppplntspm nppnqgqrgi ssvpvgrqpi imqssskfnf psgrpgmqngtgqtdfmihq

[0149] 361 nvvpagtvnr qppppyplta angqspsalq tggsaapssy tngsipqsmmvpnrnshnme

[0150] 421 lynisvpglq tnwpqsssap aqsspssghe iptwqpnipv rsnsfnnplgnrashsansq

[0151] 481 psattvtait papiqqpvks mrvlkpelqt alapthpswi pqpiqtvqpspfpegtasnv

[0152] 541 tvmppvaeap nyqgppppyp khllhqnpsv ppyesiskps kedqpslpkedeseksyenv

[0153] 601 dsgdkekkqi ttspitvrkn kkdeerresr iqsyspqafk ffmeqhvenvlkshqqrlhr

[0154] 661 kkqlenemmr vglsqdaqdq mrkmlcqkes nyirlkrakm dksmfvkiktlgigafgevc

[0155] 721 larkvdtkal yatktlrkkd vllrnqvahv kaerdilaea dnewvvrlyysfqdkdnlyf

[0156] 781 vmdyipggdm msllirmgif peslarfyia eltcavesvh kmgfihrdikpdnilidrdg

[0157] 841 hikltdfglc tgfrwthdsk yyqsgdhprq dsmdfsnewg dpsscrcgdrlkplerraar

[0158] 901 qhqrclahsl vgtpnyiape vllrtgytql cdwwsvgvil femlvgqppflaqtpletqm

[0159] 961 kvinwqtslh ippqaklspe asdliiklcr gpedrlgkng adeikahpffktidfssdlr

[0160] 1021 qqsasyipki thptdtsnfd pvdpdklwsd dneeenvndt lngwykngkhpehafyeftf

[0161] 1081 rrffddngyp ynypkpieye yinsqgseqq sdeddqntgs eiknrdlvyv

[0162] LATS1: Serine / threonine-protein kinase LATS1 isoform 2 [Homo sapiens]

[0163] NCBI Reference Sequence: NP_001257448.1 (SEQ ID NO:2)

[0164] 1 mkrsekpegy rqmrpktfpa snytvssrqm lqeireslrn lskpsdaaka ehnmskmste

[0165] 61 dprqvrnppk fgthhkalqe irnsllpfan etnssrstse vnpqmlqdlq aagfdedmvi

[0166] 121 qalqktnnrs ieaaiefisk msyqdprreq maaaaarpin asmkpgnvqq svnrkqswkg

[0167] 181 skeslvpqrh gpplgesvay hsespnsqtd vgrplsgsgi safvqahpsn gqrvnppppp

[0168] 241 qvrsvtpppp prgqtppprg ttppppswep nsqtkrysgn meyvisrisp vppgawqegy

[0169] 301 pppplntspm nppnqgqrgi ssvpvgrqpi imqssskfnf psgrpgmqng tgqtdfmihq

[0170] 361 nvvpagtvnr qppppyplta angqspsalq tggsaapssy tngsipqsmm vpnrnshnme

[0171] 421 lynisvpglq tnwpqsssap aqsspssghe iptwqpnipv rsnsfnnplg nrashsansq

[0172] 481 psattvtait papiqqpvks mrvlkpelqt alapthpswi pqpiqtvqps pfpegtasnv

[0173] 541 tvmppvaeap nyqgppppyp khllhqnpsv ppyesiskps kedqpslpke deseksyenv

[0174] 601 dsgdkekkqi ttspitvrkn kkdeerresr iqsyspqafk ffmeqhvenv lkshqqrlhr

[0175] 661 kkqlenemmr vkpfkmsifi lnhlfawclf

[0176] LATS 2: NP_055387.2 Serine / threonine-protein kinase LATS2 [Homo sapiens]. (SEQ ID NO: 3)

[0177] 1 mrpktfpatt ysgnsrqrlq eireglkqps kssvqglpag pnsdtsldak vlgskdatrq

[0178] 61 qqqmratpkf gpyqkalrei rysllpfane sgtsaaaevn rqmlqelvna gcdqemagra

[0179] 121 lkqtgsrsie aaleyiskmg yldprneqiv rvikqtspgk glmptpvtrr psfegtgdsf

[0180] 181 asyhqlsgtp yegpsfgadg ptaleemprp yvdylfpgvg phgpghqhqh ppkgygasve

[0181] 241 aagahfplqg ahygrphllv pgeplgygvq rspsfqsktp petggyaslp tkgqggppga

[0182] 301 glafpppaag lyvphphhkq agpaahqlhv lgsrsqvfas dsppqslltp srnslnvdly

[0183] 361 elgstsvqqw paatlarrds lqkpgleapp rahvafrpdc pvpsrtnsfn shqprpgppg

[0184] 421 kaepslpapn tvtavtaahi lhpvksvrvl rpepqtavgp shpawvpapa papapapapa

[0185] 481 aegldakeeh alalggagaf pldveyggpd rrcppppypk hlllrskseq ydldslcagm

[0186] 541 eqslragpne peggdksrks akgdkggkdk kqiqtspvpv rknsrdeekr esriksyspy

[0187] 601 afkffmeqhv enviktyqqk vnrrlqleqe makaglceae qeqmrkilyq kesnynrlkr

[0188] 661 akmdksmfvk iktlgigafg evclackvdt halyamktlr kkdvlnrnqv ahvkaerdil

[0189] 721 aeadnewvvk lyysfqdkds lyfvmdyipg gdmmsllirm evfpehlarf yiaeltlaie

[0190] 781 svhkmgfihr dikpdnilid ldghikltdf glctgfrwth nskyyqkgsh vrqdsmepsd

[0191] 841 lwddvsncrc gdrlktleqr arkqhqrcla hslvgtpnyi apevllrkgy tqlcdwwsvg

[0192] 901 vilfemlvgq ppflaptpte tqlkvinwen tlhipaqvkl speardlitk lccsadhrlg

[0193] 961 rngaddlkah pffsaidfss dirkqpapyv ptishpmdts nfdpvdeesp wndasegstk

[0194] 1021 awdtltspnn khpehafyef tfrrffddng ypfrcpkpsg aeasqaessdlessdlvdqt

[0195] 1081 egcqpvyv

[0196] LATS is thought to negatively regulate YAP1 activity. "YAP1" refers to yes-associated protein 1, also known as YAP or YAP65, a protein that acts as a transcriptional regulator of genes involved in cell proliferation. LATS kinase is a serine / threonine protein kinase that has been shown to directly phosphorylate YAP, which leads to YAP cytoplasmic retention and inactivation. In the absence of LATS phosphorylation, YAP translocates to the nucleus, forms a complex with the DNA-binding protein TEAD, and leads to downstream gene expression. (Barry ER & Camargo FD (2013) The Hippo superhighway: signaling crossroads converging on the Hippo / Yap pathway in stem cells and development. Current opinion in cell biology 25(2):247-253.; Mo JS, Park HW, & Guan KL (2014) The Hippo signaling pathway in stem cell biology and cancer. EMBO reports 15(6):642-656; Pan D (2010) The hipposignaling pathway in development and cancer. Developmental cell 19(4):491-505.)

[0197] The Hippo / YAP pathway is involved in multiple cell types and tissues in mammalian systems, including various cancers. In particular, the Hippo pathway is clearly involved in the intestine, stomach and esophagus, pancreas, salivary glands, skin, breast, ovary, prostate, brain and nervous system, bone, chondrocytes, adipocytes, muscle cells, T lymphocytes, B lymphocytes, myeloid cells, kidneys, and lungs. See Nishio et al., 2017, Genes to Cells 22:6-31.

[0198] LATS1 and LATS2 inhibition

[0199] Compounds of formula A1 or its subformulae, in free or salt form, are potent inhibitors of LATS1 and / or LATS2.

[0200] In preferred embodiments, compounds of formula A2 or subformulae thereof, in free or salt form, are potent inhibitors of LATS1 and LATS2.

[0201] The inhibitory potency of the compounds against LATS1 was determined by the LATS1 biochemical HTRF assay as described in Example A1 below. The inhibitory potency of the compounds of the invention against LATS1 in the assay (in micromolar LATS1 IC 50 ) are reported in Table 1A. It should be noted that IC 50 Compounds greater than 1 micromolar were considered inactive in this assay.

[0202] The inhibitory potency of selected compounds against LATS2 was determined by the LATS2 biochemical caliper assay as described in Example A3 below. The inhibitory potency of the compounds of the invention against LATS2 in the assay (in micromolar LATS2 IC50) is also reported in Table 1A. It should be noted that the IC 50 Compounds greater than 1 micromolar were considered inactive in this assay.

[0203] LATS inhibitors

[0204] Therefore, the present invention relates to compounds having the formula A2:

[0205]

[0206] or a salt or stereoisomer thereof, wherein

[0207] X 1 is CH or N;

[0208] Ring A is

[0209] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0210] A 9-membered fused bicyclic heteroaryl group selected from the following

[0211]

[0212] wherein "*" represents the point of attachment of Ring A to the rest of the molecule; and

[0213] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0214] R 0 Is hydroxyl or C 1-6 alkoxy;

[0215] R 1 is hydrogen or C 1-6 alkyl;

[0216] R 2 Selected from

[0217] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0218] (i) halogen;

[0219] (ii) cyano;

[0220] (iii) oxo;

[0221] (iv) C2 alkenyl;

[0222] (v) C2 alkynyl;

[0223] (vi)C 1-6 alkyl halide;

[0224] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0225] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0226] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0227] (x)-S(O)2C 1-6 alkyl;

[0228] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0229] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0230] (xiii) unsubstituted or halogen-substituted phenyl;

[0231] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0232] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0233] (b)-S(O)2C 1-6 alkyl;

[0234] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0235] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0236] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0237] Or, if X 1 When it is CH, R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[0238] R 3 Selected from hydrogen, halogen and C 1-6 alkyl; and

[0239] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or substituted by R 0 replace;

[0240] The conditions are:

[0241] (1) When X 1 is N, Ring A is 4-pyrimidinyl or 3-fluoro-4-pyrimidinyl, R 1 is H or methyl, R 3 is H or Cl, and R 5 is H; then R 2 Not selected from -NH2, C 1-6 substituted with an alkylamino or tert-butyl-carbamoyl-amino substituent and optionally further substituted with an unsubstituted phenyl group. 2-4 Alkyl; and

[0242] (2) When X 1is N, Ring A is indazol-5-yl, R 1 、R 3 and R 5 is H; then R 2 It is not a C4 alkyl group substituted with -NH2.

[0243] Unless otherwise indicated, the term "compound of the invention" refers to a compound of formula A2 or a subformula thereof, or a salt thereof, as well as all stereoisomers (including diastereoisomers and enantiomers), rotamers, tautomers and isotopically labeled compounds (including deuterium substitution), and inherently occurring moieties.

[0244] Various (enumerated) embodiments of the present invention are described herein. It will be appreciated that the features specified in each embodiment may be combined with other specified features to provide additional embodiments of the present invention. When an embodiment is described as "according to" a previous embodiment, the previous embodiment includes its sub-embodiments, such as when embodiment 20 is described as "according to" embodiments 1 to 19, embodiments 1 to 19 include embodiments 19 and 19A.

[0245] Example 1. The compound having formula A2 or a salt thereof as described above.

[0246] Embodiment 2. The compound of formula A2 or a salt thereof according to embodiment 1, wherein

[0247] Ring A is

[0248] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains 1 to 2 heteroatoms selected from N as ring members, provided that at least one of the nitrogen atom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0249] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0250]

[0251] wherein "*" represents the point of attachment of Ring A to the rest of the molecule; and

[0252] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2 and C 3-6 The cycloalkyl group is substituted with a substituent.

[0253] Embodiment 3. The compound of formula A2 or a salt thereof according to embodiment 1, wherein ring A is selected from

[0254] Each of which is unsubstituted or substituted with 1 to 2 independently selected from cyano, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, NH2, and C 3-6 Substitution of cycloalkyl groups;

[0255] Or selected from Each of them is unsubstituted or C 1-6 Alkyl substitution.

[0256] Embodiment 4. A compound or salt thereof according to any one of Embodiments 1 to 3 having formula A2, wherein ring A is selected from

[0257] Each of them is unsubstituted or selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Substitution with haloalkyl and -NH2 substituents;

[0258] or It is not substituted or C 1-6 Alkyl substitution.

[0259] Embodiment 5. A compound or salt thereof according to any one of Embodiments 1 to 3 having formula A2, wherein ring A is selected from

[0260]

[0261] Embodiment 6. A compound or salt thereof according to any one of Embodiments 1 to 5 having formula A2, wherein ring A is selected from

[0262]

[0263] Embodiment 7. A compound or salt thereof according to any one of Embodiments 1 to 6 having formula A2, wherein ring A is selected from

[0264]

[0265] Embodiment 8. A compound or salt thereof according to any one of Embodiments 1 to 7 having formula A2, wherein Ring A is

[0266] Embodiment 9. A compound or salt thereof according to any one of Embodiments 1 to 7 having formula A2, wherein Ring A is

[0267] Embodiment 10. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 7, wherein ring A is

[0268] Embodiment 11. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 7, wherein ring A is

[0269] Embodiment 12. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 7, wherein ring A is

[0270] Embodiment 13. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 5, wherein ring A is

[0271] Embodiment 14. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 5, wherein ring A is

[0272] Embodiment 15. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 6, wherein ring A is

[0273] Embodiment 16. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 3, wherein ring A is

[0274] Embodiment 17. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 4, wherein ring A is

[0275] Embodiment 18. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 5, wherein ring A is

[0276] Embodiment 18A. A compound of formula A2 or a salt thereof according to any one of Embodiments 1 to 5, wherein Ring A is

[0277] Embodiment 19. A compound or salt thereof according to any one of Embodiments 1 to 3 having formula A2, wherein ring A is selected from

[0278] Each of which is unsubstituted or substituted with 1 to 2 independently selected from cyano, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, NH2, and C 3-6 Substitution of cycloalkyl groups;

[0279] Or selected from Each of them is unsubstituted or C 1-6 Alkyl substitution.

[0280] Embodiment 20. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 19, wherein R 1 is selected from hydrogen, methyl and ethyl.

[0281] Embodiment 21. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 20, wherein R 1 It's methyl.

[0282] Embodiment 22. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 20, wherein R 1 It's hydrogen.

[0283] Embodiment 23. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 22, wherein

[0284] R 2 Selected from

[0285] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 Alkyl(i)cyano;

[0286] (ii) C2 alkynyl;

[0287] (iii)C 1-6 alkyl halide;

[0288] (iv)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0289] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0290] (vi)-C(O)R 8 , where R 8 It is R 0 ;

[0291] (vii)-S(O)2C 1-6 alkyl;

[0292] (viii) unsubstituted or selected from C 1-6 Alkyl, hydroxyl C1-6 Alkyl and R 0 Substituents substituted monocyclic C 3-6 Cycloalkyl;

[0293] (ix) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N and O as ring members and is unsubstituted or C 1-6 Alkyl substitution; and

[0294] (x) unsubstituted or halogen-substituted phenyl;

[0295] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0296] (c) a 4-membered heterocycloalkyl group containing as ring members a heteroatom selected from N and O, and being unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl.

[0297] Embodiment 24. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 22, wherein

[0298] R 2 Selected from

[0299] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 Alkyl(i)cyano;

[0300] (ii) C2 alkynyl;

[0301] (iii)C 1-6 alkyl halide;

[0302] (iv)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6alkyl;

[0303] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0304] (vi)-C(O)R 8 , where R 8 It is R 0 ;

[0305] (vii)-S(O)2C 1-6 alkyl;

[0306] (viii) unsubstituted or selected from C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and R 0 Substituents substituted monocyclic C 3-6 Cycloalkyl;

[0307] (ix) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N and O as ring members and is unsubstituted or C 1-6 Alkyl substitution; and

[0308] (x) unsubstituted or halogen-substituted phenyl;

[0309] And among them C 1-8 The C atom of the alkyl group is unsubstituted or substituted with 1 to 3 substituents (i) to (x), and is R 2 a point of attachment to the remainder of the molecule that is not a -CH2- group;

[0310] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0311] (c) a 4-membered heterocycloalkyl group containing as ring members a heteroatom selected from N and O, and being unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl.

[0312] Embodiment 25. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 23, wherein

[0313] R 2 Selected from

[0314] (a) unsubstituted or substituted with 1 to 2 substituents independently selected from the following C 1-8 Alkyl(i)cyano;

[0315] (ii) C2 alkynyl;

[0316] (iii)C 1-6 alkyl halide;

[0317] (iv)-OR 6 , where R 6 selected from hydrogen, unsubstituted or substituted C 1-6 alkyl;

[0318] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)-C 1-6 Alkoxy, and unsubstituted or substituted C 1-6 Alkyl; and

[0319] (vi) unsubstituted or hydroxy-substituted monocyclic C 3-6 cycloalkyl; and

[0320] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, and unsubstituted or hydroxy or -C(O)-C 1-6 Alkoxy-substituted C 1-6 alkyl.

[0321] Embodiment 26. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 25, wherein

[0322] R 2Selected from

[0323] (a) unsubstituted or substituted with 1 to 2 substituents independently selected from the following C 1-8 alkyl

[0324] (i)C 1-6 alkyl halide;

[0325] (ii)-OR 6 , where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C 1-6 Alkyl; and

[0326] (iii) unsubstituted or hydroxy-substituted monocyclic C 3-6 cycloalkyl; and

[0327] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0328] Embodiment 27. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26, wherein R 2 is unsubstituted or substituted with 1 to 2 independently selected 1-6 Haloalkyl and -OR 6 Substituents substituted C 1-8 Alkyl, where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0329] Embodiment 28. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 27, wherein R 2 is unsubstituted or hydroxy-substituted C 1-8 alkyl.

[0330] Embodiment 29. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 27, wherein R 2 Is unsubstituted or C 1-6 Haloalkyl substituted C 1-6 alkyl.

[0331] Embodiment 30. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 27, wherein R 2 Is unsubstituted or -OC 1-6 Alkyl-OH substituted C 1-6 alkyl.

[0332] Embodiment 31. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26, wherein R 2 is unsubstituted or substituted with a substituent selected from the following C 3-6 Cycloalkyl: C 1-6 Halogenated alkyl, C 1-6 Alkylamino, R 0 and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0333] Embodiment 32. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26 and 31, wherein R 2 is unsubstituted C 3-6 Cycloalkyl.

[0334] Embodiment 33. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26 and 31, wherein R 2 It is C 1-6 Alkyl or C 1-6 Haloalkyl substituted C 3-6 Cycloalkyl.

[0335] Embodiment 34. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 25, wherein R 2 isopropyl, sec-butyl, tert-butyl, 2-methyl-but-2-yl, 2,4,4-trimethylpent-2-yl,

[0336]

[0337] Where “*” represents R 2 The point of attachment to the rest of the molecule.

[0338] Embodiment 34A. A compound of formula A2 or a salt thereof according to any one of Embodiments 1 to 25, wherein R 2 Selected from

[0339] Embodiment 35. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 23 and 25 to 27, wherein R 2 Selected from n-propyl, isopropyl, tert-butyl,

[0340] Embodiment 36. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 27, 34 and 35, wherein R 2 Selected from

[0341]

[0342] Embodiment 37. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 27, 29 and 34 to 36, wherein R 2 yes

[0343] Embodiment 38. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 27, 30 and 34 to 36, wherein R 2 yes

[0344] Embodiment 39. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 27, 31 and 34 to 36, wherein R 2 yes

[0345] Embodiment 40. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26, 31, 34 and 35, wherein R 2 Selected from

[0346] Embodiment 41. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26, 31, 33 to 35 and 40, wherein R 2 Selected from

[0347] Embodiment 42. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26, 31, 33 to 35 and 40, wherein R 2 yes

[0348]

[0349] Embodiment 43. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 26, 31, 32, 34, 35 and 40, wherein R 2 yes

[0350] Embodiment 44. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 23, 25 to 30 and 35, wherein R 2 Selected from n-propyl, isopropyl and tert-butyl.

[0351] Embodiment 45. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 23, 25 to 30, 35, and 44, wherein R 2 It's n-propyl.

[0352] Embodiment 46. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 30, 35 and 44, wherein R 2 It is isopropyl.

[0353] Embodiment 47. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 30, 35 and 44, wherein R 2 It is tert-butyl.

[0354] Embodiment 48. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 19, wherein

[0355] X 1 is CH; and

[0356] R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 substituted by a substituent.

[0357] Embodiment 49. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 19 and 48, wherein

[0358] X 1 is CH; and

[0359] R 1 and R 2 Together with the nitrogen atoms to which they are both bound, they form a 5- or 6-membered heterocycloalkyl group which may contain 1 to 2 further heteroatoms selected from N, O and S as ring members, wherein R 1 and R 2 The 5- or 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from hydroxy, C 1-4 Alkyl, and C 1-4 The substituents of the haloalkyl group are substituted.

[0360] Embodiment 50. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 19, 48 and 49, wherein

[0361] X 1 is CH; and

[0362] R 1and R 2 Together with the nitrogen atom to which both are bound, a 6-membered heterocycloalkyl group is formed, which may contain other heteroatoms selected from N and O as ring members, wherein R 1 and R 2 The 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from hydroxy, C 1-6 Alkyl, and C 1-6 The substituents of the haloalkyl group are substituted.

[0363] Embodiment 51. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 19 and 48 to 50, wherein

[0364] X 1 is CH; and

[0365] R 1 and R 2 Together with the nitrogen atoms to which they are bound, they form a 6-membered heterocycloalkyl group selected from piperidinyl, piperazinyl and morpholinyl, wherein the piperidinyl, piperazinyl or morpholinyl is unsubstituted or substituted with 1 to 3 groups independently selected from hydroxyl and C 1-6 The alkyl group is substituted with a substituent.

[0366] Embodiment 52. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 51, wherein R 3 is selected from hydrogen, chlorine and methyl.

[0367] Embodiment 53. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 52, wherein R 3 It's hydrogen.

[0368] Embodiment 53A. A compound of formula A2 or a salt thereof according to any one of Embodiments 1 to 52, wherein R 3 It's chlorine.

[0369] Embodiment 53B. A compound of formula A2 or a salt thereof according to any one of Embodiments 1 to 52, wherein R 3 It's methyl.

[0370] Embodiment 54. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 53, wherein R 5 Selected from hydrogen and chlorine.

[0371] Embodiment 55. A compound of formula A2 or a salt thereof according to any one of embodiments 1 to 54, wherein R 5 It's hydrogen.

[0372] Embodiment 56. The compound of formula A2 or a salt thereof according to embodiment 1, wherein the compound has formula A3:

[0373]

[0374] in

[0375] X 1 is CH or N;

[0376] Ring A is Each of which is unsubstituted or selected from halogen, C 1-6 Alkyl, C 1-6 Substitution with haloalkyl and -NH2 substituents;

[0377] R 1 is hydrogen or unsubstituted C 1-6 alkyl; and

[0378] R 2 yes

[0379] (a) C is unsubstituted or substituted with one substituent selected from the following 1-8 alkyl

[0380] (i)C 1-4 Haloalkyl and

[0381] (ii)-OR 6 , where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C 1-6 alkyl; or

[0382] (b) unsubstituted or C 1-6 Alkyl or C 1-6 Monocyclic C substituted with haloalkyl 3-6 Cycloalkyl.

[0383] Embodiment 57. The compound of formula A2 or a salt thereof according to embodiment 56, wherein ring A is

[0384] Embodiment 58. The compound of formula A2 or a salt thereof according to embodiment 56 or embodiment 57, wherein R 2 yes

[0385]

[0386] Embodiment 59. The compound of formula A2 or a salt thereof according to embodiment 56 or embodiment 57, wherein R 2 is n-propyl or tert-butyl which is unsubstituted or substituted with trifluoromethyl.

[0387] Embodiment 60. A compound of formula A2 according to embodiment 1 or a salt thereof is selected from N-(2-cyclopropylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N,N-diethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (Pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methoxy-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxy-2-methylbutyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-butyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; 2-methyl N-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; N-ethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-cyclohexylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(3-methyloxetan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl -3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; N-butyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methyl-4-phenylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methanesulfonyl-2-methylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol;3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)acetic acid; (1R,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; 4,4,4-trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-(1-methylsulfonyl-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (2S)- 3,3,3-Trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-[(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)amino]acetic acid; (2R)-3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; methyl 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoate; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)amino]acetic acid -yl]amino}cyclopentan-1-ol; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-(2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethoxy)ethan-1-ol; 2-(hydroxymethyl)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol; 3-methyl-3-(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanamide)butanoic acid; 2-(pyridin-4-yl)-N-(1,1,1-trifluoro-3-phenylpropan-2-yl)- pyrido[3,4-d]pyrimidin-4-amine; N-{[4-(dimethylamino)oxiran-4-yl]methyl}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyric acid; N-(2-methylsulfonylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(adamantan-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propionamide;4,4,4-Trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanoic acid; N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propane-2-sulfonamide; 2-(pyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; -2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4,4,4-trifluoro-2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; (1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentyl)methanol; N-(3-methoxycyclobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (1R,2R)-1-N ,2-N-dimethyl-1-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]cyclohexane-1,2-diamine; methyl (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; ethyl 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylic acid; (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylic acid; 2-( [3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-(1,1,1-trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[ ...2-(Pyridin-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; N-(butan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylbutan-3-yn-2-yl)-2-(pyridin-4-yl)pyrido[3, 4-d]pyrimidin-4-amine; (1r,3s)-3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutan-1-ol; 2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(pyridin-4-yl)-N-(2,4,4-trimethylpentan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(pentan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-methyl-1-(morpholin-4-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine ; N-[1-(tert-Butoxy)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4,4,4-trifluoro-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-pentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-[1-(1H-indol-3-yl)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[1-(4-fluorophenyl)-2-methylpropan- [2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-phenylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(4-fluorophenyl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethan-1-ol;N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 1-({[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}methyl)cyclopentan-1-ol; N,N-dimethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-phenyl-2-(pyridin-4-yl) Pyrido[3,4-d]pyrimidin-4-amine; N-(3-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 6-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}hexanoic acid; N-(3-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanoic acid; N-(1-phenylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N -(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl N-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)carbamate; (1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; methyl 2-(1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)acetate; N-(2-methylpropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol [3,4-d]pyrimidin-4-yl]amino}butyronitrile; N-(6-aminohexyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-aminobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propionitrile; N-[2-methyl-1-(2-methylpiperidin-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine;N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-[4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl]pyridin-2-amine; 2-[1-(phenylsulfonyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-N-tert-butylpyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-methylpyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(2-methylbutan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl}amino)pentan-2-ol; N-ethyl-2-(3-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine 2-Methyl-1-[2-methyl-2-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl}amino)propoxy]propan-2-ol; 2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1-methoxy-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 4- {[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; 2-(3-chloropyridin-4-yl)-N-cyclopentylpyrido[3,4-d]pyrimidin-4-amine; 1-(2-{[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2-methylpropoxy)-2-methylpropan-2-ol; N-methyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(4-methylsulfonyl-2-methylbutan-2-yl)pyrido[3,4-d]pyrimidin-4-amine;N-tert-butyl-2-[3-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[2-chloro-5-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine -amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridin-2-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine 2-(2-fluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(1H-indazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3,5-dimethyl-1H-pyrazol-4-yl)-N- -(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1,1,1-trifluoro-2-methylpropan-2-yl)-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(4-hydroxy-2,4-dimethylpentan-2-yl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-(3,5-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2,3-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine;N-(1-methylcyclopropyl)-2-(1,3-thiazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-[2-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-2-carbonitrile; N-(1-methylcyclopropyl)-2-(1,2-oxazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(dimethyl-1,2-oxazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H- Pyrrolo[2,3-b]pyridin-4-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[3,2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclobutyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyrimidin-4-yl) Pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; N-propyl-2-{7H-pyrrolo[2,3-d]pyrimidin-5-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-cyclopropyl-1H-pyrazol-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-{1-methyl- 1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-[(1R)-1-phenylethyl]-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(5-methyl-1H-pyrazol-4-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine;2-(1-methyl-1H-pyrazol-5-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyridazin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1 ,3-oxazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H-pyrrolo[3,2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-1,2,3-triazol-4-yl)pyrido[3, 4-d]pyrimidin-4-amine; 2-(3-methyl-1,2-oxazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(2H-1,2,3,4-tetrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol ; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclobutyl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; 2-(1H-pyrazol-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine;(1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; (1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)methanol; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-4-yl)-N-(2-methylpropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine -4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-amino-2-methylpropan-2-yl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 5-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d] Pyrimidin-4-amine; 2-(2-{[4-(tert-butylamino)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-5-yl]amino}ethoxy)ethan-1-ol; N-(4-methoxy-2-methylbutan-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[2-methyl-1-(propan-2-yloxy)propan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2S)-butan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2R)-butan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methoxy-2-methylpropan- 2-(pyridin-4-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butan-1-ol; N-tert-butyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2,2-dimethyl-1-[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]piperidin-4-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}pentan-2-ol; N-cyclopentyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine;Dimethyl(3-methyl-3-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butyl)amine; N,N-diethyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}propoxy)propan-2-ol; N-propyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin- 4-amine; N-tert-butyl-2-{1H-pyrrolo[2,3-b]pyridin-4-yl}-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyridazin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyridin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine; N,N-diethyl-2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-amine; (3-{[2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-yl]amino}-3-methylbutyl)dimethylamine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)-1,7-naphthyridin-4-amine; 2-(3-fluoropyridin-4-yl)-4-(piperidin- 1-[2-(3-fluoropyridin-4-yl)-1,7-naphthyridine-4-yl]-2,2-dimethylpiperidin-4-ol; 2-(3-fluoropyridin-4-yl)-4-(morpholin-4-yl)-1,7-naphthyridine-4-amine; N-tert-butyl-2-(3-fluoropyridin-4-yl)-1,7-naphthyridine-4-amine; 2-(3-fluoropyridin-4-yl)-N-(2-methylbutan-2-yl)-1,7-naphthyridine-4-amine; 2-{[2-(3-fluoropyridin-4-yl)-1,7-naphthyridine-4-yl]amino}-2-methylpropan-1-ol; 1-[2-(3-chloropyridin-4-yl)-1,7-naphthyridine-4-yl]-2,2-dimethylpiperidin-4-ol; 2-(3-fluoropyridin-4-yl)-N-[2-methyl-1-(morpholin-4-yl)propan-2-yl]-1,7-naphthyridine- 4-amine; 4-(4-methylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 4-(piperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 4-(2-methylpiperidin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclobutyl)-1,7-naphthyridine-4-amine; 2-methyl-N1-(2-(pyridin-4-yl)-1,7-naphthyridine-4-yl)propane-1,2-diamine; N-(oxetan-3-yl)-2-(pyridin-4-yl)-1,7-naphthyridine-4-amine; N-(1-methylcyclopropyl)-2-(pyridin-4-yl)-1,7-naphthyridine-4-amine;4-(3,3-dimethylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2,2-dimethyl-4-(2-(pyridin-4-yl)-1,7-naphthyridine-4-yl)morpholine; N-(1-methylcyclobutyl)-2-(pyridin-4-yl)-1,7-naphthyridine-4-amine; 2,2-dimethyl-N1-(2-(pyridin-4-yl)-1,7-naphthyridine-4-yl)propane-1,3-diamine; N; 2 ,N 2 ,2-trimethyl-N 1 -(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,2-diamine; 4-(2-methylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2-methyl-N 1 -(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,3-diamine; (R)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)-1,7-naphthyridin-4-amine; N-(tert-butyl)-N-methyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methylcyclobutyl)-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; N 1 ,N 1 ,3-trimethyl-N 3 -(2-(pyrimidin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl(2-methyl-1-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propan-2-yl)carbamate; tert-butyl(2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)ethyl)carbamate; 2-methyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine; N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)ethane-1,2-diamine; N,N,2-trimethyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; N 1 ,3-dimethyl-N 1-(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl(2,2-dimethyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propyl)carbamate; 2,2-dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butanamide; (R)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; 2,3-dimethyl-N 2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine; (S)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; ethyl 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanoate; N 1 ,N 1 ,2,2-tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 4-(4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; N 2 ,N 2 ,2-trimethyl-N 1-(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine; 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; (S)-1,1,1-trifluoro-2-methyl-3-((2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)amino)propan-2-ol; N-tert-butyl-2-(3-chloropyridin-4-yl)amino)propanamide N-((1R,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (S)-N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1S,2R)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine (R)-N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1S,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1R,2R)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine 4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl (3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butyl)carbamate; N 1 ,N 1 ,N 3 ,2,2-pentamethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; N 1 ,N 1 -Diethyl-3-methyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; N 3 -(2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; N 1,N 1 ,3-trimethyl-N 3 -(2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-aminopyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; and 3-methyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine.

[0388] Embodiment 60A. A compound of formula A2 according to embodiment 1, or a salt thereof, selected from N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyridin-4-ol; Idio[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)piperazin-1-yl )pyrido[3,4-d]pyrimidine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; N-(1-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine;N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0389] Embodiment 60B. A compound of formula A2 according to embodiment 1 or a salt thereof is selected from N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0390] Embodiment 60C. A compound of Formula A2 or a salt thereof according to Embodiment 1 wherein the compound is N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine.

[0391] Example 61. A compound having formula I or a salt thereof

[0392]

[0393] in

[0394] Ring A is

[0395] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0396] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0397]

[0398] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0399] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0400] R 0 Is hydroxyl or C 1-6 alkoxy;

[0401] R1 is hydrogen or C 1-6 alkyl;

[0402] R 2 Selected from

[0403] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0404] (i) halogen;

[0405] (ii) cyano;

[0406] (iii) oxo;

[0407] (iv) C2 alkenyl;

[0408] (v) C2 alkynyl;

[0409] (vi)C 1-6 alkyl halide;

[0410] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0411] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0412] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0413] (x)-S(O)2C 1-6 alkyl;

[0414] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0415] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0416] (xiii) unsubstituted or halogen-substituted phenyl;

[0417] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0418] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0419] (b)-S(O)2C 1-6 alkyl;

[0420] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0421] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0422] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C1-6 alkyl;

[0423] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[0424] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or substituted by R 0 replace;

[0425] The conditions are:

[0426] (1) When ring A is 4-pyrimidinyl or 3-fluoro-4-pyrimidinyl, R 1 is H or methyl, R 3 is H or Cl, and R 5 is H; then R 2 Not selected from -NH2, C 1-6 substituted with an alkylamino or tert-butyl-carbamoyl-amino substituent and optionally further substituted with an unsubstituted phenyl group. 2-4 Alkyl; and

[0427] (2) When ring A is indazol-5-yl, R 1 、R 3 and R 5 is H; then R 2 It is not a C4 alkyl group substituted with -NH2.

[0428] Embodiment 62. The compound of formula I or a salt thereof according to embodiment 61, wherein

[0429] Ring A is

[0430] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains 1 to 2 heteroatoms selected from N as ring members, provided that at least one of the nitrogen atom ring members is an unsubstituted nitrogen (-N=) in the 3-position or 5-position relative to the attached carbon ring member of the 5-membered heteroaryl group or in the para ring position for a 6-membered heteroaryl group; or

[0431] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0432]

[0433] wherein "*" represents the point of attachment of Ring A to the rest of the molecule and Ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2 and C3-6 The cycloalkyl group is substituted with a substituent.

[0434] Embodiment 63. The compound of formula I or a salt thereof according to embodiment 61 or embodiment 62, wherein ring A is selected from

[0435] Each of which is unsubstituted or substituted with 1 to 2 independently selected from cyano, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, NH2, and C 3-6 Substitution of cycloalkyl groups;

[0436] Or selected from Each of them is unsubstituted or C 1-6 Alkyl substitution.

[0437] Embodiment 64. A compound of formula I or a salt thereof according to any one of embodiments 61 to 63, wherein ring A is selected from

[0438] Each of them is unsubstituted or selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Substitution with haloalkyl and -NH2 substituents;

[0439] or It is not substituted or C 1-6 Alkyl substitution.

[0440] Embodiment 65. A compound of formula I or a salt thereof according to any one of embodiments 61 to 63, wherein ring A is selected from

[0441]

[0442] Embodiment 66. A compound of formula I or a salt thereof according to any one of embodiments 61 to 65, wherein ring A is selected from

[0443]

[0444] Embodiment 67. A compound of formula I or a salt thereof according to any one of embodiments 61 to 66, wherein ring A is selected from

[0445]

[0446] Embodiment 68. A compound of formula I or a salt thereof according to any one of embodiments 61 to 67, wherein ring A is

[0447] Embodiment 69. A compound of formula I or a salt thereof according to any one of embodiments 61 to 67, wherein ring A is

[0448] Embodiment 70. A compound of formula I or a salt thereof according to any one of embodiments 61 to 67, wherein ring A is

[0449] Embodiment 71. A compound of formula I or a salt thereof according to any one of embodiments 61 to 67, wherein ring A is

[0450] Embodiment 72. A compound of formula I or a salt thereof according to any one of embodiments 61 to 67, wherein ring A is

[0451] Embodiment 73. A compound of formula I or a salt thereof according to any one of embodiments 61 to 65, wherein ring A is

[0452] Embodiment 74. A compound of formula I or a salt thereof according to any one of embodiments 61 to 65, wherein ring A is

[0453] Embodiment 75. A compound of formula I or a salt thereof according to any one of embodiments 61 to 66, wherein ring A is

[0454] Embodiment 76. A compound of formula I or a salt thereof according to any one of embodiments 61 to 63, wherein ring A is

[0455] Embodiment 77. A compound of formula I or a salt thereof according to any one of embodiments 61 to 64, wherein ring A is

[0456] Embodiment 78. A compound of formula I or a salt thereof according to any one of embodiments 61 to 65, wherein ring A is

[0457] Embodiment 78A. A compound of formula I or a salt thereof according to any one of embodiments 61 to 65, wherein ring A is

[0458] Embodiment 79. A compound of formula I or a salt thereof according to any one of embodiments 61 to 63, wherein ring A is selected from

[0459] Each of which is unsubstituted or substituted with 1 to 2 independently selected from cyano, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, NH2, and C 3-6 Substitution of cycloalkyl groups;

[0460] Or selected from Each of them is unsubstituted or C 1-6 Alkyl substitution.

[0461] Embodiment 80. A compound of formula I or a salt thereof according to any one of embodiments 61 to 79, wherein R 1 is selected from hydrogen, methyl and ethyl.

[0462] Embodiment 81. A compound of formula I or a salt thereof according to any one of embodiments 61 to 80, wherein R 1 It's methyl.

[0463] Embodiment 82. A compound of formula I or a salt thereof according to any one of embodiments 61 to 80, wherein R 1 It's hydrogen.

[0464] Embodiment 83. A compound of formula I or a salt thereof according to any one of embodiments 61 to 82, wherein

[0465] R 2 Selected from

[0466] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0467] (i) cyano;

[0468] (ii) C2 alkynyl;

[0469] (iii)C 1-6 alkyl halide;

[0470] (iv)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0471] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0472] (vi)-C(O)R 8 , where R 8 It is R 0 ;

[0473] (vii)-S(O)2C 1-6 alkyl;

[0474] (viii) unsubstituted or selected from C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and R 0 Substituents substituted monocyclic C 3-6 Cycloalkyl;

[0475] (ix) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N and O as ring members and is unsubstituted or C 1-6 Alkyl substitution; and

[0476] (x) unsubstituted or halogen-substituted phenyl;

[0477] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0478] (c) a 4-membered heterocycloalkyl group containing as ring members a heteroatom selected from N and O, and being unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl.

[0479] Embodiment 84. A compound of formula I or a salt thereof according to any one of embodiments 61 to 82, wherein

[0480] R 2 Selected from

[0481] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 Alkyl(i)cyano;

[0482] (ii) C2 alkynyl;

[0483] (iii)C 1-6 alkyl halide;

[0484] (iv)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0485] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0486] (vi)-C(O)R 8 , where R 8 It is R 0 ;

[0487] (vii)-S(O)2C 1-6 alkyl;

[0488] (viii) unsubstituted or selected from C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and R 0 Substituents substituted monocyclic C 3-6 Cycloalkyl;

[0489] (ix) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N and O as ring members and is unsubstituted or C 1-6 Alkyl substitution; and

[0490] (x) unsubstituted or halogen-substituted phenyl;

[0491] And among them C 1-8 The C atom of the alkyl group is unsubstituted or substituted with 1 to 3 substituents (i) to (x), and is R 2 The point of attachment to the rest of the molecule that is not a -CH2- group.

[0492] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0493] (c) a 4-membered heterocycloalkyl group containing as ring members a heteroatom selected from N and O, and being unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl.

[0494] Embodiment 85. A compound of formula I or a salt thereof according to any one of embodiments 61 to 83, wherein

[0495] R 2 Selected from

[0496] (a) unsubstituted or substituted with 1 to 2 substituents independently selected from the following C 1-8 alkyl

[0497] (i) cyano;

[0498] (ii) C2 alkynyl;

[0499] (iii)C 1-6 alkyl halide;

[0500] (iv)-OR 6 , where R 6 selected from hydrogen, unsubstituted or substituted C 1-6 alkyl;

[0501] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)-C 1-6 Alkoxy, and unsubstituted or substituted C 1-6 Alkyl; and

[0502] (vi) unsubstituted or substituted monocyclic C 3-6 cycloalkyl; and

[0503] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, and unsubstituted or hydroxy or -C(O)-C1-6 Alkoxy-substituted C 1-6 alkyl.

[0504] Embodiment 86. A compound of formula I or a salt thereof according to any one of embodiments 61 to 85, wherein

[0505] R 2 Selected from

[0506] (a) unsubstituted or substituted with 1 to 2 substituents independently selected from the following C 1-8 alkyl

[0507] (i)C 1-6 alkyl halide;

[0508] (ii)-OR 6 , where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C 1-6 Alkyl; and

[0509] (iii) unsubstituted or hydroxy-substituted monocyclic C 3-6 cycloalkyl; and

[0510] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0511] Embodiment 87. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86, wherein R 2 is unsubstituted or substituted with 1 to 2 independently selected 1-6 Haloalkyl and -OR 6 Substituents substituted C 1-6 Alkyl, where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0512] Embodiment 88. A compound of formula I or a salt thereof according to any one of embodiments 61 to 87, wherein R 2 is unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0513] Embodiment 89. A compound of formula I or a salt thereof according to any one of embodiments 61 to 87, wherein R 2 Is unsubstituted or C 1-6 Haloalkyl substituted C1-6 alkyl.

[0514] Embodiment 90. A compound of formula I or a salt thereof according to any one of embodiments 61 to 87, wherein R 2 Is unsubstituted or -OC 1-6 Alkyl-OH substituted C 1-6 alkyl.

[0515] Embodiment 91. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86, wherein R 2 is unsubstituted or substituted with a substituent selected from the following C 3-6 Cycloalkyl: C 1-6 Halogenated alkyl, C 1-6 Alkylamino, R 0 and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0516] Embodiment 92. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86 and 91, wherein R 2 is unsubstituted C 3-6 Cycloalkyl.

[0517] Embodiment 93. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86 and 91, wherein R 2 It is C 1-6 Alkyl or C 1-6 Haloalkyl substituted C 3-6 Cycloalkyl.

[0518] Embodiment 94. A compound of formula I or a salt thereof according to any one of embodiments 61 to 85, wherein R 2 Selected from n-propyl, isopropyl, sec-butyl, tert-butyl, 2-methyl-but-2-yl, 2,4,4-trimethylpent-2-yl,

[0519] Where “*” represents R 2 The point of attachment to the rest of the molecule.

[0520] Embodiment 94A. A compound of formula I or a salt thereof according to any one of embodiments 61 to 85, wherein R 2 Selected from

[0521]

[0522] Embodiment 95. A compound of formula I or a salt thereof according to any one of embodiments 61 to 83 and 85 to 87, wherein R 2Selected from

[0523] n-propyl, isopropyl, tert-butyl,

[0524] Embodiment 96. A compound of formula I or a salt thereof according to any one of embodiments 61 to 87, 94 and 95, wherein R 2 Selected from

[0525]

[0526] Embodiment 97. A compound of formula I or a salt thereof according to any one of embodiments 61 to 87, 89 and 94 to 96, wherein R 2 yes

[0527] Embodiment 98. A compound of formula I or a salt thereof according to any one of embodiments 61 to 87, 90 and 94 to 96, wherein R 2 yes

[0528] Embodiment 99. A compound of formula I or a salt thereof according to any one of embodiments 61 to 87, 91 and 94 to 96, wherein R 2 yes

[0529] Embodiment 100. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86, 91, 94 and 95, wherein R 2 Selected from

[0530] Embodiment 101. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86, 91, 93 to 95 and 100, wherein R 2 yes

[0531]

[0532] Embodiment 102. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86, 91, 93 to 95 and 100, wherein R 2 yes

[0533]

[0534] Embodiment 103. A compound of formula I or a salt thereof according to any one of embodiments 61 to 86, 91 to 95, 100 and 102, wherein R 2 yes

[0535] Embodiment 104. A compound of formula I or a salt thereof according to any one of embodiments 61 to 83, 85 to 90 and 95, wherein R 2 Selected from n-propyl, isopropyl and tert-butyl.

[0536] Embodiment 105. A compound of formula I or a salt thereof according to any one of embodiments 61 to 83, 85 to 90, 95, and 104, wherein R 2 It's n-propyl.

[0537] Embodiment 106. A compound of formula I or a salt thereof according to any one of embodiments 61 to 90, 95 and 104, wherein R 2 It is isopropyl.

[0538] Embodiment 107. A compound of formula I or a salt thereof according to any one of embodiments 61 to 90, 95 and 104, wherein R 2 It is tert-butyl.

[0539] Embodiment 108. A compound of formula I or a salt thereof according to any one of embodiments 61 to 107, wherein R 3 is selected from hydrogen, chlorine and methyl.

[0540] Embodiment 109. A compound of formula I or a salt thereof according to any one of embodiments 61 to 108, wherein R 3 It's hydrogen.

[0541] Embodiment 109A. A compound of formula I or a salt thereof according to any one of embodiments 61 to 108, wherein R 3 It's chlorine.

[0542] Embodiment 109B. A compound of formula I or a salt thereof according to any one of embodiments 61 to 108, wherein R 3 It's methyl.

[0543] Embodiment 110. A compound of formula I or a salt thereof according to any one of embodiments 61 to 109, wherein R 5 Selected from hydrogen and chlorine.

[0544] Embodiment 111. A compound of formula I or a salt thereof according to any one of embodiments 61 to 110, wherein R 5 It's hydrogen.

[0545] Embodiment 112. The compound of formula I or a salt thereof according to embodiment 61, wherein the compound has formula V:

[0546]

[0547] in

[0548] Ring A is Each of which is unsubstituted or selected from halogen, C 1-6 Alkyl, C 1-6 Substitution with haloalkyl and -NH2 substituents;

[0549] R 1 is hydrogen or unsubstituted C 1-6 alkyl; and

[0550] R 2 yes

[0551] (a) C is unsubstituted or substituted with one substituent selected from the following 1-8 alkyl

[0552] (i)C 1-4 haloalkyl or

[0553] (ii)-OR 6 , where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C 1-6 alkyl; or

[0554] (b) unsubstituted or C 1-6 Alkyl or C 1-6 Monocyclic C substituted with haloalkyl 3-6 Cycloalkyl.

[0555] Embodiment 113. The compound of formula I or a salt thereof according to embodiment 112, wherein ring A is selected from

[0556]

[0557] Embodiment 114. The compound of formula I or a salt thereof according to embodiment 112 or embodiment 113, wherein ring A is

[0558] Embodiment 115. The compound of formula I or a salt thereof according to embodiment 112 or embodiment 113, wherein ring A is

[0559] Embodiment 116. A compound of formula I or a salt thereof according to any one of embodiments 112 to 115, wherein R 2 Selected from

[0560] Embodiment 116A. A compound of formula I or a salt thereof according to any one of embodiments 112 to 115, wherein R 2 Selected from

[0561]

[0562] Embodiment 117. A compound of formula I or a salt thereof according to any one of embodiments 112 to 116, wherein R 2 yes

[0563]

[0564] Embodiment 118. A compound of formula I or a salt thereof according to any one of embodiments 112 to 116, wherein R 2 yes

[0565] Embodiment 119. A compound of formula I or a salt thereof according to any one of embodiments 112 to 116, wherein R 2 yes

[0566] Embodiment 120. A compound of formula I according to embodiment 61, or a salt thereof, selected from N-(2-cyclopropylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N,N-diethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; -(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methoxy-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxy-2-methylbutyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-butyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; 2-methyl N-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; N-ethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-cyclohexylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(3-methyloxetan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl -3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; N-butyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methyl-4-phenylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methanesulfonyl-2-methylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol;3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)acetic acid; (1R,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; 4,4,4-trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-(1-methylsulfonyl-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (2S)- 3,3,3-Trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-[(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)amino]acetic acid; (2R)-3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; methyl 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoate; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)amino]acetic acid -yl]amino}cyclopentan-1-ol; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-(2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethoxy)ethan-1-ol; 2-(hydroxymethyl)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol; 3-methyl-3-(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanamide)butanoic acid; 2-(pyridin-4-yl)-N-(1,1,1-trifluoro-3-phenylpropan-2-yl)- pyrido[3,4-d]pyrimidin-4-amine; N-{[4-(dimethylamino)oxiran-4-yl]methyl}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyric acid; N-(2-methylsulfonylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(adamantan-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propionamide;4,4,4-Trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanoic acid; N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propane-2-sulfonamide; 2-(pyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; -2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4,4,4-trifluoro-2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; (1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentyl)methanol; N-(3-methoxycyclobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (1R,2R)-1-N ,2-N-dimethyl-1-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]cyclohexane-1,2-diamine; methyl (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; ethyl 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylic acid; (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylic acid; 2-( [3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-(1,1,1-trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; [3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[ ...2-(Pyridin-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; N-(butan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylbutan-3-yn-2-yl)-2-(pyridin-4-yl)pyrido[3, 4-d]pyrimidin-4-amine; (1r,3s)-3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutan-1-ol; 2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(pyridin-4-yl)-N-(2,4,4-trimethylpentan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(pentan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-methyl-1-(morpholin-4-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine ; N-[1-(tert-Butoxy)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4,4,4-trifluoro-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-pentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-[1-(1H-indol-3-yl)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[1-(4-fluorophenyl)-2-methylpropan- [2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-phenylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(4-fluorophenyl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethan-1-ol;N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 1-({[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}methyl)cyclopentan-1-ol; N,N-dimethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-phenyl-2-(pyridin-4-yl) Pyrido[3,4-d]pyrimidin-4-amine; N-(3-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 6-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}hexanoic acid; N-(3-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanoic acid; N-(1-phenylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N -(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl N-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)carbamate; (1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; methyl 2-(1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)acetate; N-(2-methylpropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol [3,4-d]pyrimidin-4-yl]amino}butyronitrile; N-(6-aminohexyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-aminobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propionitrile; N-[2-methyl-1-(2-methylpiperidin-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine;N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-[4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl]pyridin-2-amine; 2-[1-(phenylsulfonyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-N-tert-butylpyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-methylpyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(2-methylbutan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl}amino)pentan-2-ol; N-ethyl-2-(3-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine 2-Methyl-1-[2-methyl-2-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl}amino)propoxy]propan-2-ol; 2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1-methoxy-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 4- {[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; 2-(3-chloropyridin-4-yl)-N-cyclopentylpyrido[3,4-d]pyrimidin-4-amine; 1-(2-{[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2-methylpropoxy)-2-methylpropan-2-ol; N-methyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(4-methylsulfonyl-2-methylbutan-2-yl)pyrido[3,4-d]pyrimidin-4-amine;N-tert-butyl-2-[3-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[2-chloro-5-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine -amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridin-2-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine 2-(2-fluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(1H-indazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3,5-dimethyl-1H-pyrazol-4-yl)-N- -(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1,1,1-trifluoro-2-methylpropan-2-yl)-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(4-hydroxy-2,4-dimethylpentan-2-yl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-(3,5-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2,3-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine;N-(1-methylcyclopropyl)-2-(1,3-thiazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-[2-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-2-carbonitrile; N-(1-methylcyclopropyl)-2-(1,2-oxazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(dimethyl-1,2-oxazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H- Pyrrolo[2,3-b]pyridin-4-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[3,2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclobutyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyrimidin-4-yl) Pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; N-propyl-2-{7H-pyrrolo[2,3-d]pyrimidin-5-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-cyclopropyl-1H-pyrazol-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-{1-methyl- 1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-[(1R)-1-phenylethyl]-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(5-methyl-1H-pyrazol-4-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine;2-(1-methyl-1H-pyrazol-5-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyridazin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1 ,3-oxazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H-pyrrolo[3,2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-1,2,3-triazol-4-yl)pyrido[3, 4-d]pyrimidin-4-amine; 2-(3-methyl-1,2-oxazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(2H-1,2,3,4-tetrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol ; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclobutyl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; 2-(1H-pyrazol-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine;(1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; (1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)methanol; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-4-yl)-N-(2-methylpropyl)pyrido[3,4-d]pyrimidin- 4-amine; 2-(1-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-amino-2-methylpropan-2-yl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N; 1 ,N 1 ,3-trimethyl-N 3 -(2-(pyrimidin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl(2-methyl-1-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propan-2-yl)carbamate; tert-butyl(2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)ethyl)carbamate; 2-methyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine; N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)ethane-1,2-diamine; N,N,2-trimethyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; N 1 ,3-dimethyl-N 1-(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl(2,2-dimethyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propyl)carbamate; 2,2-dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butanamide; (R)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; 2,3-dimethyl-N 2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine; (S)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; ethyl 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanoate; N 1 ,N 1 ,2,2-tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 4-(4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; N 2 ,N 2 ,2-trimethyl-N 1-(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine; 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; (S)-1,1,1-trifluoro-2-methyl-3-((2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)amino)propan-2-ol; 5-chloro-N-(1-methylcyclopropyl) -2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-{[4-(tert-butylamino)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-5-yl]amino}ethoxy)ethan-1-ol; N-((1R,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (S)-N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-5-yl]amino}ethoxy)ethan-1-ol -4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1S,2R)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (R)-N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1S,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine pyrimidin-4-amine; N-((1R,2R)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl (3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butyl)carbamate; N 1 ,N 1 ,N 3 ,2,2-pentamethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; N 1 ,N 1 -Diethyl-3-methyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; N 3 -(2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; N1 ,N 1 ,3-trimethyl-N 3 -(2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-aminopyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; and 3-methyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine.

[0567] Embodiment 120A. A compound of Formula I according to Embodiment 61, or a salt thereof, selected from N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidine -4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; (1S,2S)- 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0568] Embodiment 120B. A compound of Formula I or a salt thereof according to Embodiment 61, wherein the compound is N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0569] Example 121. A compound of formula II or a salt thereof

[0570]

[0571] in

[0572] Ring A is

[0573] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0574] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0575]

[0576] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0577] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0578] R 0 Is hydroxyl or C 1-6 alkoxy;

[0579] R 1 is hydrogen or C 1-6 alkyl;

[0580] R 2 Selected from

[0581] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0582] (i) halogen;

[0583] (ii) cyano;

[0584] (iii) oxo;

[0585] (iv) C2 alkenyl;

[0586] (v) C2 alkynyl;

[0587] (vi)C 1-6 alkyl halide;

[0588] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0589] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0590] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0591] (x)-S(O)2C 1-6 alkyl;

[0592] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0593] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0594] (xiii) unsubstituted or halogen-substituted phenyl;

[0595] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0596] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0597] (b)-S(O)2C 1-6 alkyl;

[0598] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0599] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0600] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl; or

[0601] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C1-6 Haloalkyl and R 0 Substituents substituted;

[0602] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[0603] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[0604] Embodiment 122. The compound of formula II or a salt thereof according to embodiment 121, wherein

[0605] Ring A is

[0606] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains 1 to 2 heteroatoms selected from N as ring members, provided that at least one of the nitrogen atom ring members is an unsubstituted nitrogen (-N=) in the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or in the para-ring position of the 6-membered heteroaryl group; or

[0607] (b) a 9-membered fused bicyclic heteroaryl group selected from

[0608]

[0609] wherein "*" represents the point of attachment of Ring A to the rest of the molecule and the 9-membered fused bicyclic heteroaryl is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2 and C 3-6 The cycloalkyl group is substituted with a substituent.

[0610] Embodiment 123. The compound of formula II or a salt thereof according to embodiment 121 or embodiment 122, wherein ring A is selected from

[0611] Each of which is unsubstituted or substituted with 1 to 2 independently selected from cyano, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, NH2, and C 3-6 Substitution of cycloalkyl groups;

[0612] Or selected from Each of them is unsubstituted or C 1-6 Alkyl substitution.

[0613] Embodiment 124. A compound of formula II or a salt thereof according to any one of embodiments 121 to 123, wherein ring A is selected from

[0614] Each of them is unsubstituted or selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Substitution with haloalkyl and -NH2 substituents;

[0615] or It is not substituted or C 1-6 Alkyl substitution.

[0616] Embodiment 125. A compound of formula II or a salt thereof according to any one of embodiments 121 to 123, wherein ring A is selected from

[0617] Embodiment 126. A compound of formula II or a salt thereof according to any one of embodiments 121 to 125, wherein ring A is selected from

[0618]

[0619] Embodiment 127. A compound of formula II or a salt thereof according to any one of embodiments 121 to 126, wherein ring A is selected from

[0620] Embodiment 128. A compound of formula II or a salt thereof according to any one of embodiments 121 to 127, wherein ring A is

[0621] Embodiment 129. A compound of formula II or a salt thereof according to any one of embodiments 121 to 127, wherein ring A is

[0622] Embodiment 130. A compound of formula II or a salt thereof according to any one of embodiments 121 to 127, wherein ring A is

[0623] Embodiment 131. A compound of formula II or a salt thereof according to any one of embodiments 121 to 127, wherein ring A is

[0624] Embodiment 132. A compound of formula II or a salt thereof according to any one of embodiments 121 to 127, wherein ring A is

[0625] Embodiment 133. A compound of formula II or a salt thereof according to any one of embodiments 121 to 125, wherein ring A is

[0626] Embodiment 134. A compound of formula II or a salt thereof according to any one of embodiments 121 to 125, wherein ring A is

[0627] Embodiment 135. A compound of formula II or a salt thereof according to any one of embodiments 121 to 126, wherein ring A is

[0628] Embodiment 136. A compound of formula II or a salt thereof according to any one of embodiments 121 to 123, wherein ring A is

[0629] Embodiment 137. A compound of formula II or a salt thereof according to any one of embodiments 121 to 124, wherein ring A is

[0630] Embodiment 138. A compound of formula II or a salt thereof according to any one of embodiments 121 to 125, wherein ring A is

[0631] Embodiment 139. A compound of formula II or a salt thereof according to any one of embodiments 121 to 123, wherein ring A is selected from

[0632] Each of which is unsubstituted or substituted with 1 to 2 independently selected from cyano, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, NH2, and C 3-6 Substitution of cycloalkyl groups;

[0633] Or selected from Each of them is unsubstituted or C 1-6 Alkyl substitution.

[0634] Embodiment 140. A compound of formula II or a salt thereof according to any one of embodiments 121 to 139, wherein R 1 is selected from hydrogen, methyl and ethyl.

[0635] Embodiment 141. A compound of formula II or a salt thereof according to any one of embodiments 121 to 140, wherein R 1 It's methyl.

[0636] Embodiment 142. A compound of formula II or a salt thereof according to any one of embodiments 121 to 140, wherein R 1 It's hydrogen.

[0637] Embodiment 143. A compound of formula II or a salt thereof according to any one of embodiments 121 to 142, wherein

[0638] R 2 Selected from

[0639] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 Alkyl(i)cyano;

[0640] (ii) C2 alkynyl;

[0641] (iii)C 1-6 alkyl halide;

[0642] (iv)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0643] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0644] (vi)-C(O)R 8 , where R 8 It is R 0 ;

[0645] (vii)-S(O)2C 1-6 alkyl;

[0646] (viii) unsubstituted or selected from C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and R 0 Substituents substituted monocyclic C 3-6 Cycloalkyl;

[0647] (ix) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N and O as ring members and is unsubstituted or C 1-6 Alkyl substitution; and

[0648] (x) unsubstituted or halogen-substituted phenyl;

[0649] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0650] (c) a 4-membered heterocycloalkyl group containing as ring members a heteroatom selected from N and O, and being unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl.

[0651] Embodiment 144. A compound of formula II or a salt thereof according to any one of embodiments 121 to 142, wherein

[0652] R 2 Selected from

[0653] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 Alkyl(i)cyano;

[0654] (ii) C2 alkynyl;

[0655] (iii)C 1-6 alkyl halide;

[0656] (iv)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0657] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0658] (vi)-C(O)R 8 , where R 8 It is R 0 ;

[0659] (vii)-S(O)2C 1-6 alkyl;

[0660] (viii) unsubstituted or selected from C 1-6 Alkyl, hydroxyl C 1-6 Alkyl and R 0 Substituents substituted monocyclic C 3-6 Cycloalkyl;

[0661] (ix) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N and O as ring members and is unsubstituted or C 1-6 Alkyl substitution; and

[0662] (x) unsubstituted or halogen-substituted phenyl;

[0663] Among them C 1-8 The C atom of the alkyl group is unsubstituted or substituted with 1 to 3 substituents (i) to (x), and is R 2 a point of attachment to the remainder of the molecule that is not a -CH2- group;

[0664] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0665] (c) a 4-membered heterocycloalkyl group containing as ring members a heteroatom selected from N and O, and being unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl.

[0666] Embodiment 145. A compound of formula II or a salt thereof according to any one of embodiments 121 to 143, wherein

[0667] R 2Selected from

[0668] (a) unsubstituted or substituted with 1 to 2 substituents independently selected from the following C 1-8 Alkyl(i)cyano;

[0669] (ii) C2 alkynyl;

[0670] (iii)C 1-6 alkyl halide;

[0671] (iv)-OR 6 , where R 6 selected from hydrogen, unsubstituted or substituted C 1-6 alkyl;

[0672] (v)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)-C 1-6 Alkoxy, and unsubstituted or substituted C 1-6 Alkyl; and

[0673] (vi) unsubstituted or hydroxy-substituted monocyclic C 3-6 cycloalkyl; and

[0674] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, and unsubstituted or hydroxy or -C(O)-C 1-6 Alkoxy-substituted C 1-6 alkyl.

[0675] Embodiment 146. A compound of formula II or a salt thereof according to any one of embodiments 121 to 145, wherein

[0676] R 2 Selected from

[0677] (a) unsubstituted or substituted with 1 to 2 substituents independently selected from the following C 1-8 alkyl

[0678] (i)C 1-6 alkyl halide;

[0679] (ii)-OR 6 , where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C1-6 Alkyl; and

[0680] (iii) unsubstituted or hydroxy-substituted monocyclic C 3-6 cycloalkyl; and

[0681] (b) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0682] Embodiment 147. A compound of formula II or a salt thereof according to any one of embodiments 121 to 146, wherein R 2 is unsubstituted or substituted with 1 to 2 independently selected 1-6 Haloalkyl and -OR 6 Substituents substituted C 1-6 Alkyl, where R 6 selected from hydrogen, and unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0683] Embodiment 148. A compound of formula II or a salt thereof according to any one of embodiments 121 to 147, wherein R 2 is unsubstituted or hydroxy-substituted C 1-6 alkyl.

[0684] Embodiment 149. A compound of formula II or a salt thereof according to any one of embodiments 121 to 147, wherein R 2 Is unsubstituted or C 1-6 Haloalkyl substituted C 1-6 alkyl.

[0685] Embodiment 150. A compound of formula II or a salt thereof according to any one of embodiments 121 to 147, wherein R 2 Is unsubstituted or -OC 1-6 Alkyl-OH substituted C 1-6 alkyl.

[0686] Embodiment 151. A compound of formula II or a salt thereof according to any one of embodiments 121 to 146, wherein R 2 is unsubstituted or substituted with a substituent selected from the following C 3-6 Cycloalkyl: C 1-6 Halogenated alkyl, C 1-6 Alkylamino, R 0 and unsubstituted or hydroxy-substituted C1-6 alkyl.

[0687] Embodiment 152. A compound of formula II or a salt thereof according to any one of embodiments 121 to 146 and 151, wherein R 2 is unsubstituted C 3-6 Cycloalkyl.

[0688] Embodiment 153. A compound of formula II or a salt thereof according to any one of embodiments 121 to 146 and 151, wherein R 2 It is C 1-6 Alkyl or C 1-6 Haloalkyl substituted C 3-6 Cycloalkyl.

[0689] Embodiment 154. A compound of formula II or a salt thereof according to any one of embodiments 121 to 145, wherein R 2 Selected from n-propyl, isopropyl, sec-butyl, tert-butyl, 2-methyl-but-2-yl, 2,4,4-trimethylpent-2-yl,

[0690]

[0691]

[0692] Where “*” represents R 2 The point of attachment to the rest of the molecule.

[0693] Embodiment 155. A compound of formula II or a salt thereof according to any one of embodiments 121 to 143 and 145 to 147, wherein R 2 Selected from n-propyl, isopropyl, tert-butyl,

[0694] Embodiment 156. A compound of formula II or a salt thereof according to any one of embodiments 121 to 147, 154 and 155, wherein R 2 Selected from

[0695]

[0696] Embodiment 157. A compound of formula II or a salt thereof according to any one of embodiments 121 to 147, 149 and 154 to 156, wherein R 2 yes

[0697] Embodiment 158. A compound of formula II or a salt thereof according to any one of embodiments 121 to 147, 150 and 154 to 156, wherein R 2 yes

[0698] Embodiment 159. A compound of formula II or a salt thereof according to any one of embodiments 121 to 147, 151 and 154 to 156, wherein R 2 yes

[0699] Embodiment 160. A compound of formula II or a salt thereof according to any one of embodiments 121 to 146, 151, 154 and 155, wherein R 2 Selected from

[0700] Embodiment 161. A compound of formula II or a salt thereof according to any one of embodiments 121 to 146, 151, 153 to 155 and 160, wherein R 2 yes

[0701] Embodiment 162. A compound of formula II or a salt thereof according to any one of embodiments 121 to 136, 151, 153 to 155 and 160, wherein R 2 yes

[0702] Embodiment 163. A compound of formula II or a salt thereof according to any one of embodiments 121 to 136, 151, 152, 154, 155 and 160, wherein R 2 yes

[0703] Embodiment 164. A compound of formula II or a salt thereof according to any one of embodiments 121 to 133, 135 to 150, and 155, wherein R 2 Selected from n-propyl, isopropyl and tert-butyl.

[0704] Embodiment 165. A compound of formula II or a salt thereof according to any one of embodiments 121 to 143, 145 to 150, 155, and 164, wherein R 2 It's n-propyl.

[0705] Embodiment 166. A compound of formula II or a salt thereof according to any one of embodiments 121 to 150, 155 and 164, wherein R 2 It is isopropyl.

[0706] Embodiment 167. A compound of formula II or a salt thereof according to any one of embodiments 121 to 150, 155 and 164, wherein R 2 It is tert-butyl.

[0707] Embodiment 168. A compound of formula II or a salt thereof according to any one of embodiments 121 to 139, wherein R 1 and R 2 Together with the nitrogen atom to which both are bound, they form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 substituted by a substituent.

[0708] Embodiment 169. A compound of formula II or a salt thereof according to any one of embodiments 121 to 139 and 168, wherein R 1 and R 2 Together with the nitrogen atoms to which they are both bound, they form a 5- or 6-membered heterocycloalkyl group which may contain 1 to 2 further heteroatoms selected from N, O and S as ring members, wherein R 1 and R 2 The 5- or 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from hydroxy, C 1-4 Alkyl, and C 1-4 The substituents of the haloalkyl group are substituted.

[0709] Embodiment 170. A compound of formula II or a salt thereof according to any one of embodiments 121 to 139, 168 and 169, wherein R 1 and R 2 Together with the nitrogen atom to which both are bound, a 6-membered heterocycloalkyl group is formed, which may contain other heteroatoms selected from N and O as ring members, wherein R 1 and R 2 The 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from hydroxy, C 1-6 Alkyl, and C 1-6 The substituents of the haloalkyl group are substituted.

[0710] Embodiment 171. A compound of formula II or a salt thereof according to any one of embodiments 121 to 139 and 168 to 170, wherein R 1 and R 2 Together with the nitrogen atoms to which they are bound, they form a 6-membered heterocycloalkyl group selected from piperidinyl, piperazinyl and morpholinyl, wherein the piperidinyl, piperazinyl or morpholinyl is unsubstituted or substituted with 1 to 3 groups independently selected from hydroxyl and C 1-6 The alkyl group is substituted with a substituent.

[0711] Embodiment 172. A compound of formula II or a salt thereof according to any one of embodiments 121 to 171, wherein R 3 is selected from hydrogen, chlorine and methyl.

[0712] Embodiment 173. A compound of formula II or a salt thereof according to any one of embodiments 121 to 172, wherein R 3 It's hydrogen.

[0713] Embodiment 174. A compound of formula II or a salt thereof according to any one of embodiments 121 to 173, wherein R 5 Selected from hydrogen and chlorine.

[0714] Embodiment 175. A compound of formula II or a salt thereof according to any one of embodiments 121 to 174, wherein R 5 It's hydrogen.

[0715] Embodiment 176. The compound of Formula II or a salt thereof according to Embodiment 121, wherein the compound has Formula VI:

[0716]

[0717] in

[0718] Ring A is Each is unsubstituted or selected from halogen, C 1-6 Alkyl, C 1-6 Substitution with haloalkyl and -NH2 substituents;

[0719] R 1 is hydrogen or unsubstituted C 1-6 alkyl; and

[0720] R 2 yes

[0721] (a) C is unsubstituted or substituted with a substituent selected from the following 1-8 alkyl

[0722] (i) II-C 1-6 Alkylamino;

[0723] (ii)C 1-6 alkyl halide;

[0724] (iii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 Substituted C 1-6 alkyl; or

[0725] (b) unsubstituted or C1-6 Alkyl or C 1-6 Monocyclic C substituted with haloalkyl 3-6 Cycloalkyl;

[0726] or R 1 and R 2 Together with the nitrogen to which they are attached, they may form a 6-membered heterocycloalkyl group which is unsubstituted or selected from C 1-6 The alkyl group and the hydroxy group are substituted with 1 to 3 substituents.

[0727] Embodiment 177. The compound of formula II or a salt thereof according to embodiment 176, wherein ring A is

[0728] Embodiment 178. The compound of formula II or salt thereof according to embodiment 176 or embodiment 177, wherein R 2 Selected from ethyl,

[0729] Embodiment 179. A compound of formula II or a salt thereof according to any one of embodiments 176 to 178, wherein R 2 It is tert-butyl.

[0730] Embodiment 180. A compound of Formula II according to Embodiment 121, or a salt thereof, selected from N-(4-methoxy-2-methylbutan-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[2-methyl-1-(propan-2-yloxy)propan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2S)-butan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2R)-butan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methoxy-2-methylpropan-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-methyl-N-(propan-2-yloxy)propan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine. 2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butan-1-ol; N-tert-butyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butan-1-ol; N-tert-butyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]piperidin-4-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}pentan-2-ol; N-cyclopentyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; dimethyl(3-methyl-3-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butyl) Amine; N,N-diethyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}propoxy)propan-2-ol; N-propyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine; N-tert-butyl-2-{1H-pyrrolo[2,3-b]pyridin-4-yl}-1,7-naphthyridin- 4-amine; N-tert-butyl-2-(pyridazin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyridin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine; N,N-diethyl-2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-amine; (3-{[2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-yl]amino}-3-methylbutyl)dimethylamine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)-1,7-naphthyridin-4-amine; 2-(3-fluoropyridin-4-yl)-4-(piperidin-1-yl)-1,7-naphthyridin-4-amine; 2-(3-fluoropyridin-4-yl)-4-(morpholin-4-yl)-1,7-naphthyridin-4-amine;N-tert-butyl-2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-amine; 2-(3-fluoropyridin-4-yl)-N-(2-methylbutan-2-yl)-1,7-naphthyridin-4-amine; 2-{[2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-yl]amino}-2-methylpropan-1-ol; 1-[2-(3-chloropyridin-4-yl)-1,7-naphthyridin-4-yl]-2,2-dimethylpiperidin-4-ol; 2-(3-fluoropyridin-4-yl)-N-(2-methylbutan-2-yl)-1,7-naphthyridin-4-amine -[2-methyl-1-(morpholin-4-yl)propan-2-yl]-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-chloropyridin-4-yl)-1,7-naphthyridin-4-amine; and 2-(3-chloropyridin-4-yl)-N,N-diethyl-1,7-naphthyridin-4-amine. ;

[0731] Embodiment 180a. A compound of Formula II or a salt thereof according to Embodiment 121, wherein the compound is N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine.

[0732] Embodiment 181. A compound having formula A1 or a salt thereof,

[0733]

[0734] For use in eye diseases or disorders, wherein

[0735] X 1 and X 2 are each independently CH or N;

[0736] Ring A is

[0737] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0738] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0739]

[0740] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0741] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0742] R 0 Is hydroxyl or C 1-6 alkoxy;

[0743] R 1 is hydrogen or C 1-6 alkyl;

[0744] R 2 Selected from

[0745] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0746] (i) halogen;

[0747] (ii) cyano;

[0748] (iii) oxo;

[0749] (iv) C2 alkenyl;

[0750] (v) C2 alkynyl;

[0751] (vi)C 1-6 alkyl halide;

[0752] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0753] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0754] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0755] (x)-S(O)2C 1-6 alkyl;

[0756] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0757] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0758] (xiii) unsubstituted or halogen-substituted phenyl;

[0759] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0760] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0761] (b)-S(O)2C 1-6 alkyl;

[0762] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0763] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0764] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0765] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[0766] R 3 Selected from hydrogen, halogen and C 1-6 alkyl; and

[0767] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[0768] Embodiment 182. A compound of Formula A1 or a salt thereof for use in an eye disease or disorder according to Embodiment 181, wherein the compound has a formula selected from Formula I to IV:

[0769]

[0770]

[0771] Embodiment 183. A compound of Formula A1 or a salt thereof for use in an eye disease or disorder according to Embodiment 181, wherein the compound is selected from 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0772] Embodiment 184. A compound of Formula A1 or a salt thereof for use in an eye disease or disorder according to Embodiment 181, wherein the compound is a compound according to any one of Embodiments 1 to 180.

[0773] Example 185. Compounds of Formula A1 or salts thereof

[0774]

[0775] Use in a method of generating, preferably ex vivo, an expanded limbal stem cell population, wherein

[0776] X 1 and X 2 are each independently CH or N;

[0777] Ring A is

[0778] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0779] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0780]

[0781] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0782] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0783] R 0 Is hydroxyl or C 1-6 alkoxy;

[0784] R 1 is hydrogen or C 1-6 alkyl;

[0785] R 2 Selected from

[0786] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0787] (i) halogen;

[0788] (ii) cyano;

[0789] (iii) oxo;

[0790] (iv) C2 alkenyl;

[0791] (v) C2 alkynyl;

[0792] (vi)C 1-6 alkyl halide;

[0793] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0794] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0795] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0796] (x)-S(O)2C 1-6 alkyl;

[0797] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0798] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0799] (xiii) unsubstituted or halogen-substituted phenyl;

[0800] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0801] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0802] (b)-S(O)2C 1-6 alkyl;

[0803] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0804] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0805] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0806] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[0807] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[0808] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[0809] Example 186. Compounds of Formula A1 or their salts

[0810]

[0811] Use in a method of producing, preferably ex vivo, an expanded corneal endothelial cell population, wherein

[0812] X 1 and X 2 are each independently CH or N;

[0813] Ring A is

[0814] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0815] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0816]

[0817] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0818] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0819] R 0 Is hydroxyl or C 1-6 alkoxy;

[0820] R 1 is hydrogen or C 1-6 alkyl;

[0821] R 2 Selected from

[0822] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0823] (i) halogen;

[0824] (ii) cyano;

[0825] (iii) oxo;

[0826] (iv) C2 alkenyl;

[0827] (v) C2 alkynyl;

[0828] (vi)C 1-6 alkyl halide;

[0829] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0830] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R0 Substituted C 1-6 alkyl;

[0831] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0832] (x)-S(O)2C 1-6 alkyl;

[0833] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0834] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0835] (xiii) unsubstituted or halogen-substituted phenyl;

[0836] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0837] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0838] (b)-S(O)2C 1-6 alkyl;

[0839] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0840] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0841] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0842] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[0843] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[0844] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[0845] Embodiment 187. The use of a compound of Formula A1 or a salt thereof according to Embodiment 185 or 186, wherein the compound has a formula selected from Formula I to IV:

[0846]

[0847] Embodiment 188. The use of a compound of Formula A1 or a salt thereof according to Embodiment 185 or 186, wherein the compound is selected from 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; and 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine.

[0848] Embodiment 188A. The use of a compound of Formula AI or a salt thereof according to Embodiment 185 or 186, wherein the compound is selected from: N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol. pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 2-(Pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3 ,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine and N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine. ;

[0849] Embodiment 188B. The use of a compound of Formula AI or a salt thereof according to Embodiment 185 or 186, wherein the compound is selected from: N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0850] Embodiment 188C. The use of a compound of Formula AI or a salt thereof according to Embodiment 185 or 186 wherein the compound is N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine.

[0851] Embodiment 189. Use of a compound of formula A1 or a salt thereof according to embodiment 185 or 186, wherein the compound is according to any one of embodiments 1 to 180.

[0852] Embodiment 190. A method of treating an eye disease or disorder, the method comprising administering to a subject in need thereof a cell population, wherein the cell population has been grown in the presence of a compound having Formula A1 or a salt thereof,

[0853]

[0854] in

[0855] X 1 and X 2 are each independently CH or N;

[0856] Ring A is

[0857] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0858] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0859]

[0860] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0861] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0862] R 0 Is hydroxyl or C 1-6 alkoxy;

[0863] R 1 is hydrogen or C 1-6 alkyl;

[0864] R 2 Selected from

[0865] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0866] (i) halogen;

[0867] (ii) cyano;

[0868] (iii) oxo;

[0869] (iv) C2 alkenyl;

[0870] (v) C2 alkynyl;

[0871] (vi)C 1-6 alkyl halide;

[0872] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0873] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0874] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C1-6 Alkyl-C(O)R 0 ;

[0875] (x)-S(O)2C 1-6 alkyl;

[0876] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0877] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0878] (xiii) unsubstituted or halogen-substituted phenyl;

[0879] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0880] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0881] (b)-S(O)2C 1-6 alkyl;

[0882] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0883] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6Alkyl; and

[0884] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0885] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[0886] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[0887] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[0888] Embodiment 190A. A method of treating an ocular disease or disorder, the method comprising administering to a subject in need thereof a population of limbal stem cells, wherein the population has been grown in the presence of a compound having Formula A1 or a salt thereof,

[0889]

[0890] in

[0891] X 1 and X 2 are each independently CH or N;

[0892] Ring A is

[0893] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0894] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0895]

[0896] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0897] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0898] R 0 Is hydroxyl or C 1-6 alkoxy;

[0899] R 1 is hydrogen or C 1-6 alkyl;

[0900] R 2 Selected from

[0901] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0902] (i) halogen;

[0903] (ii) cyano;

[0904] (iii) oxo;

[0905] (iv) C2 alkenyl;

[0906] (v) C2 alkynyl;

[0907] (vi)C 1-6 alkyl halide;

[0908] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0909] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0910] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0911] (x)-S(O)2C 1-6 alkyl;

[0912] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted by 1-2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0913] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0914] (xiii) unsubstituted or halogen-substituted phenyl;

[0915] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0916] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0917] (b)-S(O)2C 1-6 alkyl;

[0918] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0919] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0920] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0921] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[0922] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[0923] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[0924] Embodiment 191. A method of treating an ocular disease or disorder, the method comprising administering to a subject in need thereof a population of corneal endothelial cells, wherein the population has been grown in the presence of a compound having Formula A1 or a salt thereof,

[0925]

[0926] in

[0927] X 1 and X 2 are each independently CH or N;

[0928] Ring A is

[0929] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0930] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0931]

[0932] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0933] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0934] R 0 Is hydroxyl or C 1-6 alkoxy;

[0935] R 1 is hydrogen or C 1-6 alkyl;

[0936] R 2 Selected from

[0937] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0938] (i) halogen;

[0939] (ii) cyano;

[0940] (iii) oxo;

[0941] (iv) C2 alkenyl;

[0942] (v) C2 alkynyl;

[0943] (vi)C 1-6 alkyl halide;

[0944] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0945] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0946] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0947] (x)-S(O)2C 1-6 alkyl;

[0948] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0949] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0950] (xiii) unsubstituted or halogen-substituted phenyl;

[0951] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0952] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0953] (b)-S(O)2C 1-6 alkyl;

[0954] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0955] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0956] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0957] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[0958] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[0959] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[0960] Embodiment 192. The method of treating an eye disease or disorder according to embodiment 190 or 191, wherein the compound has a formula selected from Formula I to IV:

[0961]

[0962] Embodiment 193. The method of treating an eye disease or disorder according to embodiment 190 or 191, wherein the compound is selected from 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0963] Embodiment 193A. The method of treating an eye disease or disorder according to embodiment 190 or 191, wherein the compound is selected from: N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol. -yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 2- (Pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3, (4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine and N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine. ;

[0964] Embodiment 193B. The method of treating an eye disease or disorder according to embodiment 190 or 191, wherein the compound is selected from: N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[0965] Embodiment 193C. The method of treating an eye disease or disorder according to Embodiment 190 or 191 wherein the compound is N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine.

[0966] Embodiment 194. The method of promoting cell proliferation according to embodiment 190 or 191, wherein the compound is according to any one of embodiments 1 to 180.

[0967] Example 195. A compound of formula A1 or a salt thereof,

[0968]

[0969] Use in the manufacture of a medicament for an eye disease or disorder, wherein

[0970] X 1 and X 2 are each independently CH or N;

[0971] Ring A is

[0972] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[0973] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[0974]

[0975] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[0976] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[0977] R 0 Is hydroxyl or C 1-6 alkoxy;

[0978] R 1 is hydrogen or C 1-6 alkyl;

[0979] R 2 Selected from

[0980] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[0981] (i) halogen;

[0982] (ii) cyano;

[0983] (iii) oxo;

[0984] (iv) C2 alkenyl;

[0985] (v) C2 alkynyl;

[0986] (vi)C 1-6 alkyl halide;

[0987] (vii)-OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[0988] (viii)-NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[0989] (ix)-C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[0990] (x)-S(O)2C 1-6 alkyl;

[0991] (xi) Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0992] (xii) 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[0993] (xiii) unsubstituted or halogen-substituted phenyl;

[0994] (xiv) 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[0995] (xv) 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[0996] (b)-S(O)2C 1-6 alkyl;

[0997] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[0998] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[0999] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1000] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[1001] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[1002] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[1003] Embodiment 196. Use of a compound of Formula A1 or a salt thereof according to Embodiment 195 in the manufacture of a medicament for an eye disease or disorder, wherein the compound has a formula selected from Formula I to IV:

[1004]

[1005] Embodiment 197. Use of a compound of Formula A1 according to Embodiment 195 or a salt thereof in the manufacture of a medicament for an eye disease or disorder, wherein the compound is selected from 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; and 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine.

[1006] Embodiment 197A. Use of a compound of Formula AI or a salt thereof according to Embodiment 195 in the manufacture of a medicament for an eye disease or disorder, wherein the compound is selected from: N-methyl-2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridine- 4-amine; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl -1-ol; 2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)pyrido[3,4-d]pyrimidine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine] [3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine and N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine. ;

[1007] Embodiment 197B. Use of a compound of Formula AI or a salt thereof according to Embodiment 195 in the manufacture of a medicament for an eye disease or disorder, wherein the compound is selected from: N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; and N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

[1008] Embodiment 197C. Use of a compound of Formula AI or a salt thereof according to Embodiment 195 in the manufacture of a medicament for an eye disease or disorder, wherein the compound is N-(tert-butyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine.

[1009] Embodiment 198. Use of a compound of formula A1 or a salt thereof according to embodiment 195, wherein the compound is according to any one of embodiments 1 to 180, for the manufacture of a medicament for an eye disease or disorder.

[1010] Example 199. A compound of formula A1 or a pharmaceutically acceptable salt thereof,

[1011]

[1012] For promoting liver regeneration and liver regrowth,

[1013] X 1 and X 2 are each independently CH or N;

[1014] Ring A is

[1015] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[1016] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[1017]

[1018] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[1019] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[1020] R 0 Is hydroxyl or C 1-6 alkoxy;

[1021] R 1 is hydrogen or C 1-6 alkyl;

[1022] R 2 Selected from

[1023] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[1024] halogen;

[1025] cyano group;

[1026] Oxo;

[1027] C2 alkenyl;

[1028] C2 alkynyl;

[1029] C 1-6 alkyl halide;

[1030] -OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1031] -NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[1032] -C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R0 ;

[1033] -S(O)2C 1-6 alkyl;

[1034] Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1035] 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1036] unsubstituted or halogen-substituted phenyl;

[1037] 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[1038] 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[1039] (b)-S(O)2C 1-6 alkyl;

[1040] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[1041] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[1042] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1043] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[1044] R 3 Selected from hydrogen, halogen and C 1-6 Alkyl; and

[1045] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[1046] Embodiment 200. A compound of formula A1 or a pharmaceutically acceptable salt thereof for use in promoting liver regeneration and liver regeneration according to embodiment 199, wherein the compound has a formula selected from formula I to IV:

[1047]

[1048] Embodiment 201. A compound of formula A1 or a pharmaceutically acceptable salt thereof for use in promoting liver regeneration and liver regeneration and growth according to embodiment 199, wherein the compound is selected from:

[1049] 2-Methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol;

[1050] dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine;

[1051] N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1052] 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1053] 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1054] N-(tert-Butyl)-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1055] 5-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1056] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1057] N-tert-Butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine;

[1058] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1059] 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine;

[1060] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1061] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1062] 2,2-Dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1063] 2,3-Dimethyl-N2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine;

[1064] N 1 ,N 1 ,2,2-tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1065] 4-(4-(tert-Butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; and

[1066] N 2 ,N 2 ,2-trimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine.

[1067] Embodiment 202. The compound of formula A1 or a pharmaceutically acceptable salt thereof for use in promoting liver regeneration and liver regeneration and growth according to embodiment 199, wherein the compound is according to any one of embodiments 1 to 180.

[1068] Example 203. Compounds of Formula A1 or pharmaceutically acceptable salts thereof

[1069]

[1070] Use for promoting liver regeneration and liver regeneration growth, wherein

[1071] X 1 and X 2 are each independently CH or N;

[1072] Ring A is

[1073] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[1074] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[1075]

[1076] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[1077] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[1078] R 0 Is hydroxyl or C 1-6 alkoxy;

[1079] R 1 is hydrogen or C 1-6 alkyl;

[1080] R 2 Selected from

[1081] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[1082] halogen;

[1083] cyano group;

[1084] Oxo;

[1085] C2 alkenyl;

[1086] C2 alkynyl;

[1087] C 1-6 alkyl halide;

[1088] -OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1089] -NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[1090] -C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[1091] -S(O)2C 1-6 alkyl;

[1092] Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1093] 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1094] unsubstituted or halogen-substituted phenyl;

[1095] 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[1096] 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[1097] (b)-S(O)2C 1-6 alkyl;

[1098] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[1099] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[1100] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1101] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[1102] R 3 Selected from hydrogen, halogen and C 1-6 alkyl; and

[1103] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[1104] Embodiment 204. Use of a compound of Formula A1 or a pharmaceutically acceptable salt thereof according to Embodiment 203 for promoting liver regeneration and liver regeneration growth, wherein the compound has a formula selected from Formula I to IV:

[1105]

[1106] Embodiment 205. Use of a compound of formula A1 or a pharmaceutically acceptable salt thereof according to embodiment 203 for promoting liver regeneration and liver regeneration growth, wherein the compound is selected from:

[1107] 2-Methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol;

[1108] dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine;

[1109] N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1110] 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1111] 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1112] N-(tert-Butyl)-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1113] 5-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1114] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1115] N-tert-Butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine;

[1116] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1117] 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine;

[1118] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1119] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1120] 2,2-Dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1121] 2,3-Dimethyl-N2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine;

[1122] N 1 ,N 1 ,2,2-tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1123] 4-(4-(tert-Butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; and

[1124] N 2 ,N 2 ,2-trimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine.

[1125] Embodiment 206. Use of a compound of formula A1 according to embodiment 203 or a pharmaceutically acceptable salt thereof for promoting liver regeneration and liver regeneration growth, wherein the compound is according to any one of embodiments 1 to 180.

[1126] Example 207. A method of promoting liver regeneration and liver re-growth, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having Formula A1 or a pharmaceutically acceptable salt thereof,

[1127]

[1128] in

[1129] X 1 and X 2 are each independently CH or N;

[1130] Ring A is

[1131] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[1132] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[1133]

[1134] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[1135] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[1136] R 0 Is hydroxyl or C 1-6 alkoxy;

[1137] R 1 is hydrogen or C 1-6 alkyl;

[1138] R 2 Selected from

[1139] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[1140] halogen;

[1141] cyano group;

[1142] Oxo;

[1143] C2 alkenyl;

[1144] C2 alkynyl;

[1145] C 1-6 alkyl halide;

[1146] -OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1147] -NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[1148] -C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R0 ;

[1149] -S(O)2C 1-6 alkyl;

[1150] Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1151] 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1152] unsubstituted or halogen-substituted phenyl;

[1153] 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[1154] 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[1155] (b)-S(O)2C 1-6 alkyl;

[1156] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[1157] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[1158] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1159] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[1160] R 3 Selected from hydrogen, halogen and C 1-6 alkyl; and

[1161] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[1162] Embodiment 208. The method of promoting liver regeneration and liver re-growth according to embodiment 207, wherein the compound has a formula selected from Formula I to IV:

[1163]

[1164] Embodiment 209. The method for promoting liver regeneration and liver re-growth according to embodiment 207, wherein the compound is selected from:

[1165] 2-Methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol;

[1166] dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine;

[1167] N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1168] 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1169] 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1170] N-(tert-Butyl)-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1171] 5-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1172] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1173] N-tert-Butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine;

[1174] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1175] 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine;

[1176] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1177] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1178] 2,2-Dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1179] 2,3-Dimethyl-N2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine;

[1180] N 1 ,N 1 ,2,2-tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1181] 4-(4-(tert-Butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; and

[1182] N 2 ,N 2 ,2-trimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine.

[1183] Embodiment 210. The method of promoting liver regeneration and liver re-growth according to embodiment 207, wherein the compound is according to any one of embodiments 1 to 180.

[1184] Example 211. Compounds of Formula A1 or pharmaceutically acceptable salts thereof

[1185]

[1186] Use in the manufacture of a medicament for promoting liver regeneration and liver regeneration growth, wherein

[1187] X 1 and X 2 are each independently CH or N;

[1188] Ring A is

[1189] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[1190] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[1191]

[1192] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[1193] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[1194] R 0 Is hydroxyl or C 1-6 alkoxy;

[1195] R 1 is hydrogen or C 1-6 alkyl;

[1196] R 2 Selected from

[1197] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[1198] halogen;

[1199] cyano group;

[1200] Oxo;

[1201] C2 alkenyl;

[1202] C2 alkynyl;

[1203] C 1-6 alkyl halide;

[1204] -OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1205] -NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[1206] -C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[1207] -S(O)2C 1-6 alkyl;

[1208] Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C 1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1209] 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1210] unsubstituted or halogen-substituted phenyl;

[1211] 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[1212] 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[1213] (b)-S(O)2C 1-6 alkyl;

[1214] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[1215] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[1216] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1217] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[1218] R 3 Selected from hydrogen, halogen and C 1-6 alkyl; and

[1219] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[1220] Embodiment 212. Use of a compound of formula A1 or a pharmaceutically acceptable salt thereof according to embodiment 211 in the manufacture of a medicament for promoting liver regeneration and liver regeneration growth, wherein the compound has a formula selected from formula I to IV:

[1221]

[1222] Embodiment 213. Use of a compound of formula A1 or a pharmaceutically acceptable salt thereof according to embodiment 211 in the manufacture of a medicament for promoting liver regeneration and liver regeneration growth, wherein the compound is selected from:

[1223] 2-Methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol;

[1224] dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine;

[1225] N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1226] 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1227] 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1228] N-(tert-Butyl)-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1229] 5-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;

[1230] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1231] N-tert-Butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine;

[1232] N-tert-Butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine;

[1233] 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine;

[1234] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1235] N 1 ,N 1 ,3-trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine;

[1236] 2,2-Dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1237] 2,3-Dimethyl-N 2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine;

[1238] N 1 ,N 1 ,2,2-tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine;

[1239] 4-(4-(tert-Butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; and

[1240] N 2 ,N 2 ,2-trimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,2-diamine.

[1241] Embodiment 214. Use of a compound of formula A1 according to embodiment 211 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for promoting liver regeneration and liver regeneration and growth, wherein the compound is according to any one of embodiments 1 to 180.

[1242] In another embodiment, the present invention relates to a pharmaceutical composition comprising at least one compound of the present invention or a pharmaceutically acceptable salt thereof.

[1243] In another embodiment, the present invention relates to a pharmaceutical composition comprising at least one compound of the present invention or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier, diluent or excipient.

[1244] In another embodiment, the present invention relates to a compound of the present invention or a pharmaceutically acceptable salt or pharmaceutical composition thereof for use as a medicament.

[1245] In another embodiment, the present invention relates to a pharmaceutical composition for promoting liver regeneration and liver regeneration growth, comprising a compound having Formula A1 or its subformulae or a pharmaceutically acceptable salt thereof.

[1246] In another embodiment, the present invention also relates to the use of a compound of formula A1 or its subformula or a pharmaceutically acceptable salt thereof, alone or optionally in combination with another compound of formula A1 or its subformula or a pharmaceutically acceptable salt thereof and / or at least one other type of therapeutic agent, in the preparation of a medicament for promoting liver regeneration and liver regeneration and growth.

[1247] In another embodiment, the present invention relates to a method of promoting liver regeneration and liver re-growth, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula A1 or its subformulae, or a pharmaceutically acceptable salt thereof.

[1248] In another embodiment, the present invention relates to a method for: promoting liver regeneration and liver regrowth, particularly for treating insufficient liver regrowth after marginal graft transplantation; for supporting enhanced regrowth of the remaining liver mass after extensive hepatectomy; for regeneration of the liver in patients following acute liver failure caused by viral hepatitis, drug-induced liver injury, autoimmune hepatitis, ischemic and congestive liver disease; for treating patients with chronic liver injury and underlying liver fibrosis caused by non-alcoholic steatohepatitis, alcoholic steatohepatitis, chronic viral hepatitis B and C, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease and drug-induced liver fibrosis to enhance regenerative capacity and accelerate fibrosis regression.

[1249] In another embodiment, the present invention relates to a method for promoting liver regeneration and liver re-growth, comprising administering to a subject in need thereof a therapeutically effective amount of an agent capable of inhibiting the activity of LATS1 and LATS2 kinases; thereby inducing YAP translocation and driving downstream gene expression to promote cell proliferation. In another embodiment, the agent is a compound having Formula A1 or its subformulae, or a pharmaceutically acceptable salt thereof.

[1250] In another embodiment, the present invention relates to a method for promoting liver regeneration and liver re-growth, comprising administering to a subject in need thereof a therapeutically effective amount of an agent capable of inhibiting LATS kinase activity; thereby inducing YAP translocation and driving downstream gene expression to promote cell proliferation. In a preferred embodiment, the agent is a compound according to any one of embodiments 1 to 180.

[1251] In another embodiment, the present invention relates to a method for ex vivo expansion of a hepatocyte population, comprising contacting the hepatocytes with a compound according to any one of embodiments 1 to 180. In a preferred embodiment, the method further comprises gene editing the hepatocytes. Preferably, the gene editing targets genes associated with host anti-transplantation immune responses.

[1252] In another embodiment, the present invention relates to a method for ex vivo expansion of a hepatic progenitor cell population, the method comprising contacting the hepatic progenitor cells with a compound according to any one of embodiments 1 to 180. In a preferred embodiment, the method further comprises gene editing the hepatic progenitor cells. Preferably, the gene editing targets genes associated with host anti-transplantation immune responses.

[1253] In another embodiment, the present invention relates to a population of hepatocytes obtained by contacting hepatocytes with a compound according to any one of embodiments 1 to 180. In a preferred embodiment, the hepatocytes obtained by contacting hepatocytes with a compound according to any one of embodiments 1 to 180 have been gene-edited. Preferably, the gene editing targets genes related to host anti-transplantation immune responses.

[1254] In another embodiment, the present invention relates to a population of hepatic progenitor cells obtained by contacting hepatic progenitor cells with a compound according to any one of Examples 1 to 180. In a preferred embodiment, the hepatic progenitor cells obtained by contacting hepatic progenitor cells with a compound according to any one of Examples 1 to 180 have been gene-edited. Preferably, the gene editing targets genes related to host anti-transplantation immune responses.

[1255] Embodiment 215. A compound having formula A1 or a pharmaceutically acceptable salt thereof,

[1256]

[1257] To promote wound healing,

[1258] X 1 and X 2 are each independently CH or N;

[1259] Ring A is

[1260] (a) a 5- or 6-membered monocyclic heteroaryl group which is attached to the remainder of the molecule via a carbon ring member and contains from 1 to 4 heteroatoms independently selected from N, O and S as ring members, provided that at least one of the heteroatom ring members is an unsubstituted nitrogen (-N=) at the 3- or 4-position of the 5-membered heteroaryl group relative to the attached carbon ring member or at the para ring position of the 6-membered heteroaryl group; or

[1261] (b) a 9-membered fused bicyclic heteroaryl group selected from the following

[1262]

[1263] where “*” represents the point of attachment of Ring A to the rest of the molecule;

[1264] wherein ring A is unsubstituted or substituted with 1 to 2 groups independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Haloalkyl, -NH2, C 1-6 Alkylamino, di-(C 1-6 Alkyl)amino, C 3-6 Substitution of cycloalkyl and phenylsulfonyl groups;

[1265] R0 Is hydroxyl or C 1-6 alkoxy;

[1266] R 1 is hydrogen or C 1-6 alkyl;

[1267] R 2 Selected from

[1268] (a) unsubstituted or substituted with 1 to 3 substituents independently selected from the following C 1-8 alkyl

[1269] halogen;

[1270] cyano group;

[1271] Oxo;

[1272] C2 alkenyl;

[1273] C2 alkynyl;

[1274] C 1-6 alkyl halide;

[1275] -OR 6 , where R 6 Selected from hydrogen, unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 alkyl;

[1276] -NR 7a R 7b , where R 7a is hydrogen or C 1-6 Alkyl, and R 7b Selected from hydrogen, -C(O)R 0 , unsubstituted or -C(O)R 0 Substituted C 1-6 alkyl;

[1277] -C(O)R 8 , where R 8 It is R 0 or -NH-C 1-6 Alkyl-C(O)R 0 ;

[1278] -S(O)2C 1-6 alkyl;

[1279] Monocyclic C 3-6 Cycloalkyl or polycyclic C 7-10 Cycloalkyl, each of which is unsubstituted or substituted with 1 to 2 independently selected halogen, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, C1-6 Haloalkyl, R 0 、-NH2、C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1280] 6-membered heterocycloalkyl, which contains 1 to 2 heteroatoms independently selected from N, O and S as ring members and is unsubstituted or substituted with 1 to 2 heteroatoms independently selected from hydroxy, halogen, C 1-6 Alkyl, C 1-6 Alkylamino and di-(C 1-6 substituted with a substituent of an alkyl)amino group;

[1281] unsubstituted or halogen-substituted phenyl;

[1282] 5- or 6-membered monocyclic heteroaryl containing 1 to 4 heteroatoms independently selected from N and O as ring members; and

[1283] 9- or 10-membered fused bicyclic heteroaryl containing 1 to 2 heteroatoms independently selected from N and O as ring members;

[1284] (b)-S(O)2C 1-6 alkyl;

[1285] (c) unsubstituted or substituted with 1 to 2 independently selected from halogen, C 1-6 Alkyl and R 0 a phenyl group substituted with a substituent;

[1286] (d) C is unsubstituted or substituted with 1 to 2 substituents independently selected from the following 3-6 Cycloalkyl: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C 1-6 Alkyl; and

[1287] (e) 4-membered heterocycloalkyl, which contains 1 to 2 heteroatoms selected from N, O and S as ring members, and is unsubstituted or substituted with 1 to 2 substituents independently selected from: C 1-6 Haloalkyl, R 0 、C 1-6 Alkylamino, di-(C 1-6 alkyl)amino, -C(O)R 0 and unsubstituted or R 0 or -C(O)R 0 Substituted C1-6 alkyl;

[1288] or R 1 and R 2 Together with the nitrogen atom to which both are bound, they may form a 4- to 6-membered heterocycloalkyl group which may contain 1 to 2 other heteroatoms independently selected from N, O and S as ring members, wherein R 1 and R 2 The 4- to 6-membered heterocycloalkyl group formed together with the nitrogen atoms to which both are bound is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, C 1-6 Alkyl, C 1-6 Haloalkyl and R 0 Substituents substituted;

[1289] R 3 Selected from hydrogen, halogen and C 1-6 alkyl; and

[1290] R 5 is selected from hydrogen, halogen and -NH-(3 to 8 membered heteroalkyl), wherein the 3 to 8 membered heteroC 3-8 The alkyl group contains 1 to 2 oxygen atoms as chain members and is unsubstituted or R 0 replace.

[1291] Embodiment 216. A compound of formula A1 or a pharmaceutically acceptable salt thereof for use in promoting wound healing according to embodiment 215, wherein the compound has a formula selected from formula I to IV:

[1292]

[1293] Embodiment 217. A compound of formula A1 for use in promoting wound healing according to embodiment 215, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from 3-(pyridin-4-yl)-N-(1-(trifluoromethyl)cyclopropyl)-2,6-naphthyridin-1-amine; N-(1-methylcyclopropyl)-7-(pyridin-4-yl)isoquinolin-5-amine; 2-(pyridin-4-yl)-4-(3-(trifluor...

Claims

1. A compound or a salt thereof, wherein the compound is selected from N-(2-cyclopropylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N,N-diethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(pyridin-4-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; Idio[3,4-d]pyrimidin-4-amine; N-(1-methoxy-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxy-2-methylbutyl-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-butyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; 2-methyl-1-(2 -methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; N-ethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-cyclohexylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(3-methyloxetane-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3- {[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; N-butyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methyl-4-phenylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopropyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methanesulfonyl-2-methylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol;3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)acetic acid; (1R,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; 4,4,4-trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-(1-methylsulfonyl-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (2S)- 3,3,3-Trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-[(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)amino]acetic acid; (2R)-3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; methyl 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoate; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4 -yl]amino}cyclopentan-1-ol; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-(2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethoxy)ethan-1-ol; 2-(hydroxymethyl)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propane-1,3-diol; 3-methyl-3-(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butanamide)butanoic acid; 2-(pyridin-4-yl)-N-(1,1,1-trifluoro-3-phenylpropan-2- 4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-{[4-(dimethylamino)oxiran-4-yl]methyl}-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyric acid; N-(2-methylsulfonylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(adamantan-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propionamide;4,4,4-Trifluoro-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyric acid; N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]propane-2-sulfonamide; 2-(pyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazol-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; -2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4,4,4-trifluoro-2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; (1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentyl)methanol; N-(3-methoxycyclobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (1R,2R)-1-N ,2-N-dimethyl-1-N-[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]cyclohexane-1,2-diamine; methyl (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; ethyl 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; 1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylate; (1s,3s)-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutane-1-carboxylic acid; 2-( pyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylbutan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine;2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; N-(butan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylbutan-3-yn-2-yl)-2-(pyridin-4-yl)pyrido[3, 4-d]pyrimidin-4-amine; (1r,3s)-3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutan-1-ol; 2,3-dimethyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-2-ol; 2-(pyridin-4-yl)-N-(2,4,4-trimethylpentan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(pentan-3-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-methyl-1-(morpholin-4-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine ; N-[1-(tert-butyloxy)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4,4,4-trifluoro-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-pentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butan-1-ol; N-[1-(1H-indol-3-yl)-2-methylpropan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[1-(4-fluorophenyl)-2-methylpropan- [2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-phenylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-[2-(4-fluorophenyl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3,3,3-trifluoro-2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propanoic acid; 2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}ethan-1-ol;N-methyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 1-({[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}methyl)cyclopentan-1-ol; N,N-dimethyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methylphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-methoxyphenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 6-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}hexanoic acid; N-(3-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 6-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}hexanoic acid; N-(3-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine 4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyric acid; N-(1-phenylethyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl N-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propyl)carbamate; (1-{[2-(pyridin- 4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; methyl 2-(1-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)acetate; N-(2-methylpropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyronitrile; N-(6-aminohexyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(4-aminobutyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propionitrile; N-[2-methyl-1-(2-methylpiperidin-1-yl)propan-2-yl]-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; dimethyl(3-methyl-3-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}butyl)amine; N-(1-amino-2-methylpropan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-cyclopentyl-2-[3-(trifluoromethyl)- 1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-[4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl]pyridin-2-amine; 2-[1-(phenylsulfonyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-N-tert-butylpyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-chloropyridin-4-yl)pyrido[3 ,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-methylpyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(2-methylbutyl-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-yl}amino)pentan-2-ol; N-ethyl-2-(3-fluoropyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-[2-methyl-2-({2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d] [3,4-d]pyrimidin-4-yl}amino)propoxy]propan-2-ol; 2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-ethyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1-methoxy-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; 2-(3-chloropyridin-4-yl)-N-cyclopentylpyrido[3,4-d]pyrimidin-4-amine;1-(2-{[2-(3-chloropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2-methylpropoxy)-2-methylpropan-2-ol; N-methyl-2-(3-methylpyridin-4-yl)-N-(propan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(4-methylsulfonyl-2-methylbutyl-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[3-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-[2-chloro-5-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 2 -(3-chloropyridin-4-yl)-N-[3-(1H-1,2,3,4-tetrazolyl-5-yl)propyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2S)-1,1,1 -trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-fluoropyridin-4-yl)-N-methyl-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridin-2-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; 4-{4-[(1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridin-2-amine cyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-{2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(1H-indazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3,5-dimethyl-1H-pyrazol-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1,1,1-trifluoro-2-methylpropan-2-yl)-2-[3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine;4-{4-[(4-hydroxy-2,4-dimethylpentan-2-yl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-3-carbonitrile; 2-(3,5-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2,3-difluoropyridin-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1,3-thiazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-[2-(trifluoromethyl)pyridin-4-yl]pyrido[3,4-d]pyrimidin-4-amine; 4-{4-[( [1-methylcyclopropyl)amino]pyrido[3,4-d]pyrimidin-2-yl}pyridine-2-carbonitrile; N-(1-methylcyclopropyl)-2-(1,2-oxazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(dimethyl-1,2-oxazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H-pyrrolo[2,3-b]pyridin-4-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-{1H-pyrrolo[3, 2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclobutyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyrimidin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-{[2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}-2,4-dimethylpentan-2-ol; N-propyl-2-{7H-pyrrolo[2,3 -d]pyrimidin-5-yl}pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-cyclopropyl-1H-pyrazol-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-(3-methylpyridin-4-yl)-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-N-propylpyrido[3,4-d]pyrimidin-4-amine; 2,4-dimethyl-4-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol;N-[(1R)-1-phenylethyl]-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(5-methyl-1H-pyrazol-4-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-[(1R)-1-phenylethyl]pyrido[3,4 -d]pyrimidin-4-amine; N-methyl-N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(pyridazin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1,3-oxazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-imidazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-{1H-pyrrolo[3,2-b]pyridin-1-yl}pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-1, 2-(2H-1,2,3,4-tetrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1,2-oxazol-5-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(2H-1,2,3,4-tetrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d ]pyrimidin-4-yl]amino}cyclobutyl)methanol; 2-(1-methyl-1H-pyrazol-5-yl)-N-(1-methylcyclobutyl)pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(1-methyl-1H-pyrazol-5-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; 2-(1H-pyrazol-4-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-[1-(pyridin-4-yl)ethyl] Pyrido[3,4-d]pyrimidin-4-amine; (1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclobutyl)methanol; (1-{[2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopropyl)methanol; 2-(1-methyl-1H-pyrazol-5-yl)-N-[1-(pyridin-4-yl)ethyl]pyrido[3,4-d]pyrimidin-4-amine; N-(1-methylcyclopropyl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(1-ethyl-1H-pyrazol-4-yl)-N-(2-methylpropyl)pyrido[3,4-d]pyrimidin-4-amine;2-(1-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; N-(1-amino-2-methylpropan-2-yl)-2-(1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 8-methyl-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-5-chloro-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 5-chloro-N-(1-methylcyclopropyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine 2-(2-{[4-(tert-butylamino)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-5-yl]amino}ethoxy)ethan-1-ol; N-(4-methoxy-2-methylbutyl-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[2-methyl-1-(propan-2-yloxy)propan-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2S)-butyl-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-[(2R)-butyl-2-yl]-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methoxy-2-methylbutyl-2-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine 2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)-piperidin-4-ol; 2,4-dimethyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)-piperidin-4-ol; 2-( ...-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)-piperidin-4-ol; 2-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)piperidin-4-ol; 2-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)piperidin-4-ol; 2-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)piperidin-4-ol; 2-(2-(pyridin-4 N,N-diethyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}butyl)amine; N,N-diethyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)-1,7-naphthyridin-4-yl]amino}propoxy)propan-2-ol; N-propyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyrimidin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine;N-tert-butyl-2-{1H-pyrrolo[2,3-b]pyridin-4-yl}-1,7-naphthyridin-4-amine; N-tert-butyl-2-(pyridazin-4-yl)-1,7-naphthyridin-4-amine; 2-(2-aminopyridin-4-yl)-N-tert-butyl-1,7-naphthyridin-4-amine; N,N-diethyl-2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-amine; (3-{[2-(3-fluoropyridin-4-yl)- 2-(3-fluoropyridin-4-yl)-4-(piperidin-1-yl)-1,7-naphthyridine; 2-(3-fluoropyridin-4-yl)-4-(morpholin-4-yl)-1,7-naphthyridine; N-tert-butyl-2-(3-fluoropyridin-4-yl)-N-methyl-N-(propan-2-yl)-1,7-naphthyridine )-1,7-naphthyridin-4-amine; 2-(3-fluoropyridin-4-yl)-N-(2-methylbutyl-2-yl)-1,7-naphthyridin-4-amine; 2-{[2-(3-fluoropyridin-4-yl)-1,7-naphthyridin-4-yl]amino}-2-methylpropan-1-ol; 1-[2-(3-chloropyridin-4-yl)-1,7-naphthyridin-4-yl]-2,2-dimethylpiperidin-4-ol; 2-(3-fluoropyridin-4-yl)-N-(2-methylbutyl-2-yl)-1,7-naphthyridin-4-amine -[2-methyl-1-(morpholin-4-yl)propan-2-yl]-1,7-naphthyridin-4-amine; N-tert-butyl-2-(3-chloropyridin-4-yl)-1,7-naphthyridin-4-amine; N-((1R,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (S)-N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1S,2R)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; (R)-N-(sec-butyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1S,2S)-2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-((1R,2R) -2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 4-(4-methylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 4-(piperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 4-(2-methylpiperidin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2-(pyridin-4-yl)-N -(1-(trifluoromethyl)cyclobutyl)-1,7-naphthyridin-4-amine; 2-methyl-N1-(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,2-diamine; N-(oxetane-3-yl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methylcyclopropyl)-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; 4-(3,3- dimethylpiperazine-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2,2-dimethyl-4-(2-(pyridin-4-yl)-1,7-naphthyridine-4-yl)morpholine; N-(1-methylcyclobutyl)-2-(pyridin-4-yl)-1,7-naphthyridine-4-amine; 2,2-dimethyl-N1-(2-(pyridin-4-yl)-1,7-naphthyridine-4-yl)propane-1,3-diamine; N 2 ,N 2 ,2-Trimethyl-N 1 -(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,2-diamine; 4-(2-methylpiperazin-1-yl)-2-(pyridin-4-yl)-1,7-naphthyridine; 2-methyl-N 1 -(2-(pyridin-4-yl)-1,7-naphthyridin-4-yl)propane-1,3-diamine; (R)-2-(pyridin-4-yl)-4-(3-(trifluoromethyl)piperazin-1-yl)-1,7-naphthyridine; N-(tert-butyl)-N-methyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine; N-(1-methylcyclobutyl)-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; N 1 ,N 1 ,3-Trimethyl-N 3 -(2-(pyrimidin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 1 ,N 1 ,3-Trimethyl-N 3 -(2-(3-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl(2-methyl-1-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propan-2-yl)carbamate; tert-butyl(2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)ethyl)carbamate; N,N,2-trimethyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; N 1 ,3-dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; tert-butyl(2,2-dimethyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propyl)carbamate; 2,2-dimethyl-N 1 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butanamide; 2,3-dimethyl-N 2 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-2,3-diamine; ethyl 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanoate; N 1 ,N 1 ,2,2-Tetramethyl-N 3 -(2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; 4-(4-(tert-butylamino)pyrido[3,4-d]pyrimidin-2-yl)-1,2,5-oxadiazol-3-amine; 2-methyl-2-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)propanamide; (S)-1,1,1-trifluoro-2-methyl-3-((2-(pyridin- 4-yl)-1,7-naphthyridin-4-yl)amino)propan-2-ol; 2-(3-chloropyridin-4-yl)-N,N-diethyl-1,7-naphthyridin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; tert-butyl (3-methyl-3-((2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)amino)butyl)carbamate; N 1 ,N 1 ,N 3 ,2,2-pentamethyl-N 3 -(2-(Pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)propane-1,3-diamine; N 1 ,N 1 -Diethyl-3-methyl-N 3 -(2-(Pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-fluoropyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-Trimethylbutane-1,3-diamine; N 3 -(2-(3,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-Trimethylbutane-1,3-diamine; N 1 ,N 1 ,3-Trimethyl-N 3 -(2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine; N 3 -(2-(2-aminopyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)-N 1 ,N 1 ,3-trimethylbutane-1,3-diamine; and 3-methyl-N 1 -(2-(Pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl)butane-1,3-diamine.

2. The compound of claim 1, wherein the compound is N-tert-butyl-2-(pyridin-4-yl)-1,7-naphthyridin-4-amine, or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising the compound according to any one of claims 1 to 2 as an active ingredient and at least one pharmaceutically acceptable excipient.

4. A method for inhibiting LATS in an isolated cell population comprising ocular cells using a compound of any one of claims 1-2, wherein the compound is not N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2 -ol; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)-N-[1-(trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[ 3,4-d]pyrimidin-4-yl]amino}propan-1-ol; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl) [3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine; or N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

5. The method of claim 4, wherein the ocular cells comprise limbal stem cells or corneal endothelial cells.

6. The method of claim 4, wherein the compound is present at a concentration of 0.5 to 100 micromolar.

7. The method of claim 4, wherein the compound is present at a concentration of 0.5 to 25 micromolar.

8. The method of claim 4, wherein the compound is present at a concentration of 3 to 10 micromolar.

9. The method of claim 4, wherein the method further comprises genetically modifying the ocular cells.

10. The method of claim 9, wherein the genetic modification comprises reducing or eliminating the expression or function of a gene associated with promoting host anti-transplantation immune response.

11. The method of claim 9, wherein the genetic modification comprises introducing a gene editing system into the cell, the gene editing system specifically targeting a gene associated with promoting a host anti-transplantation immune response.

12. The method according to claim 11, wherein the gene editing system is selected from: CRISPR gene editing system, TALEN gene editing system, zinc finger nuclease gene editing system, large-range nuclease gene editing system, AAV vector-driven homologous recombination and lentiviral vector-based genome editing technology.

13. The method of claim 10, wherein the gene is selected from the group consisting of: B2M, HLA-A, HLA-B, and HLA-C.

14. A method for culturing cells, the method comprising culturing a cell population comprising ocular cells in the presence of a compound as defined in any one of claims 1 to 2 or a salt thereof, wherein the compound is not 2-methyl-1-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)propan-2-ol; 2,4-dimethyl-4-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}pentan-2-ol; N-tert-butyl-2-(pyrimidin-4-yl)-1,7-naphthyridin-4-amine; 2-(pyridin-4-yl)-N-[1-( trifluoromethyl)cyclobutyl]pyrido[3,4-d]pyrimidin-4-amine; N-propyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-methyl-1H-pyrazol-4-yl)-N-(1-methylcyclopropyl)pyrido[3,4-d]pyrimidin-4-amine; 2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propan-1-ol; N-cyclopentyl-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin- 4-amine; N-propyl-2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-(2-methylcyclopentyl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(3-chloropyridin-4-yl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrido[3,4-d]pyrimidin-4-amine; 2-(2-methyl-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol; (1S,2S)-2-{[2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-yl]amino}propoxy)ethan-1-ol [3,4-d]pyrimidin-4-yl]amino}cyclopentan-1-ol; N-methyl-2-(pyridin-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine; N-methyl-N-(propan-2-yl)-2-(pyridin-4-yl)pyrido[3,4-d]pyrimidin-4-amine; N-tert-butyl-2-(3-methyl-1H-pyrazol-4-yl)-1,7-naphthyridin-4-amine; or N-methyl-2-(pyridin-4-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyrido[3,4-d]pyrimidin-4-amine.

15. The method of claim 14, wherein the ocular cells comprise limbal stem cells or corneal endothelial cells.

16. The method of claim 14, wherein the compound is present at a concentration of 0.5 to 100 micromolar.

17. The method of claim 14, wherein the compound is present at a concentration of 0.5 to 25 micromolar.

18. The method of claim 14, wherein the compound is present at a concentration of 3 to 10 micromolar.

19. The method of claim 14, further comprising genetically modifying the ocular cells.

20. The method of claim 19, wherein the genetic modification comprises reducing or eliminating the expression or function of a gene associated with promoting host anti-transplantation immune response.

21. The method of claim 19, wherein the genetic modification comprises introducing a gene editing system into the cell, the gene editing system specifically targeting a gene associated with promoting a host anti-transplantation immune response.

22. The method of claim 21, wherein the gene editing system is selected from: CRISPR gene editing system, TALEN gene editing system, zinc finger nuclease gene editing system, large-range nuclease gene editing system, AAV vector-driven homologous recombination and lentiviral vector-based genome editing technology.

23. The method of claim 20, wherein the gene is selected from the group consisting of: B2M, HLA-A, HLA-B, and HLA-C.

24. A method for expanding a cell population, the method comprising the following steps: a) culturing a seeded cell population comprising ocular cells in the presence of a compound as defined in any one of claims 1 to 2 or a salt thereof to produce an expanded cell population comprising ocular cells.

25. The method of claim 24, wherein the ocular cells comprise limbal stem cells or corneal endothelial cells.

26. The method of claim 24, wherein the compound is present at a concentration of 0.5 to 100 micromolar.

27. The method of claim 24, wherein the compound is present at a concentration of 0.5 to 25 micromolar.

28. The method of claim 24, wherein the compound is present at a concentration of 3 to 10 micromolar.

29. The method of claim 24, wherein the compound is present for one to two weeks, followed by a further step in which the cells are cultured for a period of time in growth medium not supplemented with the compound.

30. The method of claim 29, wherein the period of time is from one to two weeks.

31. The method of claim 24, wherein the method further comprises genetically modifying the ocular cells.

32. The method of claim 31, wherein the genetic modification comprises reducing or eliminating the expression or function of a gene associated with promoting a host anti-transplantation immune response.

33. The method of claim 31, wherein the genetic modification comprises introducing a gene editing system into the cell that specifically targets a gene associated with promoting a host anti-transplantation immune response.

34. The method of claim 33, wherein the gene editing system is selected from: CRISPR gene editing system, TALEN gene editing system, zinc finger nuclease gene editing system, large-range nuclease gene editing system, AAV vector-driven homologous recombination, and lentiviral vector-based genome editing technology.

35. The method of claim 34, wherein the gene is selected from the group consisting of: B2M, HLA-A, HLA-B, and HLA-C.

36. An agent for promoting the growth of ocular cells, comprising the compound or a salt thereof as defined in any one of claims 1 to 2.

37. The growth promoter of eye cells according to claim 36, wherein the eye cells comprise limbal stem cells or corneal endothelial cells.

38. A cell proliferation medium comprising a compound or a salt thereof as defined in any one of claims 1 to 2 and a growth medium.

39. The cell proliferation medium of claim 38, wherein the growth medium is selected from the group consisting of: Dulbecco's Modified Eagle's Medium supplemented with fetal bovine serum, human endothelial serum-free medium with human serum, X-VIVO 15 medium, and mesenchymal stem cell conditioned medium.

40. The cell proliferation medium of claim 39, wherein the growth medium comprises X-VIVO 15 medium.

41. The cell proliferation medium of claim 38, further comprising ocular cells.

42. The cell proliferation medium of claim 41, wherein the ocular cells comprise limbal stem cells or corneal endothelial cells.

43. A cell preparation comprising a compound or a salt thereof as defined in any one of claims 1 to 2 and ocular cells.

44. The cell preparation of claim 43, wherein the ocular cells comprise limbal stem cells or corneal endothelial cells.

45. The cell preparation according to claim 43, further comprising a growth medium, wherein the growth medium is selected from the group consisting of: Dulbecco's Modified Eagle's Medium supplemented with fetal bovine serum, human endothelial serum-free medium with human serum, X-VIVO15 medium, and mesenchymal stem cell conditioned medium.

46. ​​The cell preparation of claim 45, wherein the growth medium comprises X-VIVO15 medium.

47. The pharmaceutical composition of claim 3, further comprising a preservation solution.

48. The pharmaceutical composition of claim 47, wherein the preservation solution comprises Optisol or PBS solution.

49. The cell preparation of claim 43, further comprising a cryopreservation solution.

50. The cell preparation of claim 49, wherein the cryopreservation solution comprises Optisol or PBS solution.

51. The pharmaceutical composition of claim 3, further comprising a cryopreservation solution.

52. The pharmaceutical composition of claim 51, wherein the cryopreservation solution comprises glycerol, dimethyl sulfoxide, propylene glycol, or acetamide.

53. The cell preparation of claim 43, further comprising a cryopreservation solution.

54. The cell preparation of claim 53, wherein the cryopreservation solution comprises glycerol, dimethyl sulfoxide, propylene glycol or acetamide.

55. A kit comprising a composition suitable for ocular delivery and a compound as defined in any one of claims 1 to 2, or a salt thereof.

56. The kit of claim 55, wherein the composition suitable for ocular delivery is a spotter or topical eye drop.

57. The kit of claim 55, further comprising ocular cells.

58. The kit of claim 57, wherein the ocular cells comprise limbal stem cells or corneal endothelial cells.

59. The kit of claim 55, wherein the composition suitable for ocular delivery is a localizing agent comprising a biological matrix.

60. The kit of claim 55, wherein the composition suitable for ocular delivery is a positioning agent selected from fibrin, collagen, gelatin, cellulose, amniotic membrane, fibrin glue, polyethylene (glycol) diacrylate (PEGDA), GelMA or a hydrogel.

61. The kit of claim 55, wherein the composition suitable for ocular delivery is a positioning agent selected from a polymer.

62. The kit of claim 61, wherein the polymer is a cross-linked polymer.

63. The kit of claim 60, wherein the hydrogel comprises one or more of hyaluronic acid, polyethylene glycol, polypropylene glycol, polyethylene oxide, polypropylene oxide, poloxamers, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinyl pyrrolidone, poly(lactide-co-glycolide), alginate, gelatin, collagen, fibrinogen, methylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl guar gum, gellan gum, xanthan gum, and carboxymethyl cellulose.

64. The kit of claim 60, wherein the hydrogel comprises one or more of hyaluronic acid, polyethylene glycol, polypropylene glycol, polyethylene oxide, polypropylene oxide, poloxamers, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinyl pyrrolidone, poly(lactide-co-glycolide), alginate, gelatin, collagen, fibrinogen, cellulose, gellan gum, guar gum, and xanthan gum.

65. The kit of claim 60, wherein the composition suitable for ocular delivery is a localizing agent comprising GelMA.

66. A cell delivery formulation comprising the cell preparation of claim 43 and a composition suitable for ocular delivery as a localizing agent.

67. The cell delivery formulation of claim 66, wherein the composition suitable for ocular delivery is a localizing agent for a biological matrix.

68. The cell delivery formulation of claim 66, wherein the composition suitable for ocular delivery is a positioning agent selected from the group consisting of fibrin, collagen, gelatin, cellulose, amniotic membrane, fibrin glue, polyethylene (glycol) diacrylate (PEGDA), GelMA, or a hydrogel.

69. The cell delivery formulation of claim 66, wherein the composition suitable for ocular delivery is a positioning agent selected from a polymer.

70. The cell delivery formulation of claim 69, wherein the polymer is a cross-linked polymer.

71. The cell delivery formulation of claim 68, wherein the hydrogel comprises one or more of hyaluronic acid, polyethylene glycol, polypropylene glycol, polyethylene oxide, polypropylene oxide, poloxamers, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinyl pyrrolidone, poly(lactide-co-glycolide), alginate, gelatin, collagen, fibrinogen, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropyl guar gum, gellan gum, xanthan gum, and carboxymethylcellulose.

72. The cell delivery formulation of claim 68, wherein the hydrogel comprises one or more of hyaluronic acid, polyethylene glycol, polypropylene glycol, polyethylene oxide, polypropylene oxide, poloxamers, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyvinyl pyrrolidone, poly(lactide-co-glycolide), alginate, gelatin, collagen, fibrinogen, cellulose, gellan gum, guar gum, and xanthan gum.

73. The cell delivery formulation of claim 68, wherein the composition suitable for ocular delivery is a localizing agent as a GelMa.

74. Use of a compound as defined in any one of claims 1 to 2, or a salt thereof, for the manufacture of a medicament for the treatment of an eye disease or disorder.

75. The use according to claim 74, wherein the ocular disease or disorder is associated with reduced corneal endothelial cell density.

76. The use according to claim 74, wherein the ocular disease or disorder is corneal endothelial dysfunction.

77. The use according to claim 74, wherein the ocular disease or disorder is selected from the group consisting of: Fuchs endothelial corneal dystrophy, bullous keratopathy, corneal transplant failure, posterior polymorphic corneal dystrophy, congenital hereditary endothelial dystrophy, X-linked endothelial corneal dystrophy, aniridia and corneal endotheliitis.

78. The use according to claim 77, wherein the bullous keratopathy is pseudophakic bullous keratopathy or aphakic bullous keratopathy.

79. The use according to claim 74, wherein the ocular disease or disorder is selected from the group consisting of: Fuchs corneal endothelial dystrophy, bullous keratopathy, and corneal transplant failure.

80. The use of claim 74, wherein the eye disease or disorder is a limbal stem cell deficiency.

81. The use of claim 80, wherein the ocular disease or disorder is limbal stem cell deficiency caused by (i) an injury or disorder selected from chemical burns, thermal burns, radiation damage, aniridia, sclerokeratosis, multiple endocrine neoplasia, Stevens Johnson syndrome, ocular cicatricial pemphigoid, collagen vascular disease; (ii) limbal stem cell deficiency caused by chronic non-autoimmune inflammatory disorders caused by contact lens use, dry eye, rosacea, staphylococcal limbus, keratitis, pterygium or tumor, multiple eye surgeries, pterygium or tumor removal or cryotherapy; (iii) and limbal stem cell deficiency caused by drug toxicity caused by a drug selected from the group consisting of: Antiseptics, local anesthetics, pilocarpine, beta-blockers, mitomycin, 5-fluorouracil, silver nitrate, and oral medications that cause Stevens Johnson syndrome.

82. The use of claim 80, wherein the ocular disease or disorder is a limbal stem cell deficiency caused by an injury or disorder selected from the group consisting of chemical burns, aniridia, Stevens Johnson syndrome, and contact lens use.

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