Pharmaceutical composition for the treatment of cancer

Abstract

To provide pharmaceutical compositions for the treatment of conditions or disorders ameliorated by the inhibition of A2A / A2B receptors.SOLUTION: Provided are pharmaceutical compositions comprising compounds of Formula I and their pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof. Further provided is the use of said pharmaceutical composition for the preparation of a medicament for the treatment of a condition or disorder selected from prostate, rectal, renal, ovarian, endometrial, thyroid, pancreatic cancer, breast, colon, bladder cancer, brain, glial, melanoma, pineal, or lung cancers.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This disclosure relates to A 2A / A 2B The present disclosure relates to a pharmaceutical composition comprising a compound selected from a compound of Formula I, a compound of Formula II, a compound of Formula III, or a compound of Formula IV for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. In particular, the present disclosure relates to the use of the pharmaceutical composition for the preparation of a medicament for the treatment of a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer. [Background technology]

[0002] Adenosine is an endogenous modulator of a wide range of physiological functions and has been implicated in several pathologies. Recent advances in molecular biology, coupled with several pharmacological studies, have identified at least four subtypes of adenosine receptors: A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14, A15, A16, A17, A18, A19, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A5 2A , A 2B A1 and A3 receptors have been identified. A1 and A3 receptors downregulate cellular cAMP levels by coupling with G proteins that inhibit adenylate cyclase. In contrast, A 2A and A 2B The receptor couples to a G protein that activates adenylate cyclase, increasing intracellular cAMP levels.

[0003] Advances in our understanding of the role of adenosine and its receptors in physiology and pathophysiology, as well as new advances in the medicinal chemistry of these receptors, have revealed potential therapeutic areas for drug development. Pharmacological data using selective ligands, combined with genetically engineered mice, have led to significant progress toward understanding the role of adenosine receptors (Ar) in a variety of diseases, including inflammatory conditions, sepsis, heart attack, ischemia-reperfusion injury, vascular trauma, spinal cord injury, chronic obstructive pulmonary disease (COPD), asthma, diabetes, obesity, inflammatory bowel disease, retinopathy, and Parkinson's disease (PD).

[0004] In the central nervous system, A 2A Antagonists have antidepressant properties and can stimulate cognitive function. Epidemiological evidence indicates a protective role for caffeine in Parkinson's disease. Furthermore, A 2A The receptor density is found to be very high in the basal ganglia, which control motor control functions. 2A Antagonists can improve movement disorders caused by neurodegenerative diseases such as Parkinson's disease (Trends Pharmacol. Sci., 1997, vol. 18, pp. 338-344), senile dementia such as Alzheimer's disease, psychosis, and stroke, and may potentially be effective in treating cerebral ischemia (Life Sci., 1994, vol. 55, pp. 61-65). 2a Antagonists can also be used to treat or manage attention-related disorders such as attention deficit disorder and attention deficit hyperactivity disorder, extrapyramidal syndromes such as dystonia, akathisia, pseudoparkinsonism, and tardive dyskinesia, and abnormal movement disorders such as restless legs syndrome and periodic limb movements during sleep. Some of these indications have been disclosed in patent applications (e.g., WO 02 / 055083, WO 05 / 044245, and WO 06 / 132275). Adenosine A 2A Antagonists may also be useful in the treatment of amyotrophic lateral sclerosis, cirrhosis, fibrosis, and fatty liver (U.S. Patent Application Publication No. 2007037033, WO 01 / 058241). 2A Receptor antagonists are also useful for reducing addictive behavior (WO 06 / 009698) and for treating and preventing skin fibrosis in diseases such as scleroderma (Arthritis & Rheumatism, Vol. 54(8), pp. 2632-2642, 2006).

[0005] Parkinson's disease (PD) is a progressive, incurable disorder with no established preventative treatment, although drugs can be used to alleviate symptoms and / or slow disease progression. Among various strategies, A 2A AR blockers are considered a potential approach to the treatment of the disease. 2AAR is abundantly expressed in the striatum, nucleus accumbens, and olfactory tubercle. A is expressed in GABAergic striatopallidal neurons, where adenosine and dopamine agonists exert antagonistic effects in controlling locomotor activity. 2A Co-expression of D2 dopamine receptors has been reported. 2A Activation of the AR reduces the affinity of the D2 receptor for dopamine, antagonizing the effects of the D2 receptor. 2A Based on the negative interaction between A and D2 receptors, A is being investigated as a novel therapeutic approach for the treatment of PD. 2A Antagonists are used (Pharmacol. Ther., 2005, vol. 105, p. 267). 2A The recent discovery that A can form functional heteromeric receptor complexes with other G protein-coupled receptors, such as D2 receptors and mGlu5 receptors, has led to the development of A in PD. 2A New opportunities for potential antagonists were also suggested (J. Mol. Neurosci., 2005, 26, 209).

[0006] Adenosine signaling is known to play apoptotic, angiogenic, and pro-inflammatory roles and may be involved in the pathogenesis of asthma and chronic obstructive pulmonary disease (Trends in Pharmacological Sciences, 2003, vol. 24, p. 8). Extracellular adenosine acts as a local modulator with generally cytoprotective functions in the body. Its effects on tissue protection and repair fall into four categories: increasing the ratio of oxygen supply to demand; protecting against ischemic injury by cellular conditioning; triggering anti-inflammatory responses; and promoting angiogenesis.

[0007] In recent years, A 2AAdenosine receptors have represented an exciting advance in the development of immunotherapies for cancer treatment (Cancer Immunol Res., 2015, Vol. 3, pp. 506-517). Adenosine production in the tumor microenvironment is an active metabolic mechanism used by cancer cells to evade antitumor immune surveillance and increase metastasis. The ectonucleotidases CD73 and CD39 (highly expressed on tumor and stromal cells) convert ATP released by dying tumor cells into adenosine. 2A Adenosine signaling through the receptor enhances pro-tumor responses in the tumor microenvironment that contribute to tumor growth and metastasis. 2A The receptor is expressed on several immune cell types: T lymphocytes, dendritic cells, and natural killer cells. 2A When the receptor is activated on T cells and NK cells, it causes immunosuppression by reducing their proliferation, cytokine production, and tumoricidal activity. 2A The antagonists can induce anti-tumor responses in multiple types of cancer when used standalone or in combination with existing immunotherapies or radiotherapy or chemotherapy. 2A Cancers that may benefit from antagonist therapy include melanoma, triple-negative breast cancer, colon cancer, colorectal cancer, lung cancer, prostate cancer, renal cell cancer, non-small cell lung cancer, bladder cancer, cervical cancer, vulvar or anal cancer, esophageal cancer, metastatic head and neck cancer, liver cancer, lymphoma, multiple myeloma, ovarian cancer, pancreatic cancer, acute myeloid leukemia, and Kaposi's sarcoma.

[0008] A 2B Adenosine receptor subtypes (Feoktistov et al., I. Pharmacol. Rev., 1997, 49, 381-402) have been identified in various human and mouse tissues and are involved in the regulation of vascular tone, smooth muscle growth, angiogenesis, hepatic glucose production, bowel movements, intestinal secretion, and mast cell degranulation.

[0009] A 2BThe receptor has been implicated in mast cell activation and asthma, regulation of vascular tone, cardiomyocyte contractility, cell proliferation and gene expression, vasodilation, control of cell growth, intestinal function, and neurosecretory modulation (Pharmacological Reviews, 2003, Vol. 49, No. 4).

[0010] A 2B The receptor modulates mast cell function. Adenosine activates adenylate cyclase and protein kinase C, enhancing post-stimulation mediator release in mouse bone marrow-derived mast cells. 2B Activation of the receptor increases IL-8 release and enhances PMA-induced IL-8 secretion. Thus, adenosine contributes to the asthmatic response by inducing mast cells to release pro-inflammatory mediators (Pulmonary Pharmacology & Therapeutics, 1999, Vol. 12, pp. 111-114). In COPD, the transformation of pulmonary fibroblasts into myofibroblasts is considered to be the main mechanism. 2B Activation of AR is involved in this process. 2B Antagonists are expected to have beneficial effects on pulmonary fibrosis (Curr. Drug Targets, 2006, vol. 7, pp. 699-706; Am. J. Resper. Cell. Mol. Biol., 2005, vol. 32, p. 228). 2B Antagonists can be used as wound healing agents. 2B Activation of AR promotes angiogenesis by increasing the release of angiogenic factors, leading to A 2B Antagonists are useful for blocking angiogenesis (Circ. Res., 2002, 90, 531-538). 2BAR can be involved in the inhibition of cardiac fibroblast (CF) proliferation (Am. J. Physiol. Heart Circ. Physiol., 2004, Vol. 287, pp. H2478-H2486). Adenosine stimulates Cl secretion in the intestinal epithelium, suggesting a possible treatment for cystic fibrosis patients with CFTR mutations (Am. J. Respir. Cell Mol. Biol., 2008, Vol. 39, pp. 190-197). High-affinity A 2B The antagonist was effective in the hot plate model and inhibited A in nociception. 2B This suggests a role for steroids in the treatment of psoriasis and that they can be used as potential analgesics (The J. of Pharmacol. and Exp. Ther., 2004, 308, 358-366).

[0011] A 2B The receptor is involved in the release of IL-6. Increasing evidence suggests that IL-6 plays a role in Alzheimer's disease with respect to the inflammatory processes associated with the disease. 2B Receptor antagonists may be useful for Alzheimer's disease.

[0012] A 2B AR is Na + They are involved in stimulating nitric oxide production during glucose or glutamine absorption. They are involved in agonist-stimulated glucose production in hepatocytes. 2B Receptor antagonists have shown antidiabetic potential primarily by increasing plasma insulin levels under conditions in which adenosine tone is elevated in vivo and insulin release is increased in vitro (J Pharm. Pharmacol., 2006 December; 58(12):1639-45). Thus, A 2B Antagonists may serve as novel targets for the treatment of this metabolic disease.

[0013] A 2BAdenosine activation of adenosine receptors has been shown to increase cAMP accumulation, cell proliferation, and VEGF expression in human retinal endothelial cells. 2B Activation of AdoR increased vascular endothelial growth factor mRNA and protein expression in human retinal endothelial cells. Adenosine also exerts a synergistic effect with VEGF in vitro on retinal endothelial cell proliferation and capillary morphogenesis. Such activity is necessary for wound healing, but endothelial cell hyperproliferation contributes to diabetic retinopathy. Unwanted vascular proliferation also occurs in neoplasia. Therefore, adenosine and endothelial A 2B Inhibition of receptor binding reduces or prevents hypervascularization, thus preventing retinopathy and inhibiting tumor formation.

[0014] Adenosine production in the tumor microenvironment is an active metabolic mechanism used by cancer cells to evade antitumor immune surveillance and increase metastasis. The ectonucleotidases CD73 and CD39 (highly expressed on tumor and stromal cells) convert ATP released by dying tumor cells into adenosine. 2B The receptor is expressed at low levels in multiple cell types under normal conditions but is significantly upregulated under hypoxic conditions that prevail in the tumor microenvironment. 2B Activation of the receptor promotes angiogenesis and induces immunosuppression mediated by T cells and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. 2B The antagonists can induce anti-tumor responses in multiple types of cancer when used standalone or in combination with existing immunotherapies or radiotherapy or chemotherapy. 2B Cancers that may benefit from antagonist therapy include melanoma, triple-negative breast cancer, colon cancer, colorectal cancer, lung cancer, prostate cancer, renal cell cancer, non-small cell lung cancer, bladder cancer, cervical cancer, vulvar or anal cancer, esophageal cancer, metastatic head and neck cancer, liver cancer, lymphoma, multiple myeloma, ovarian cancer, pancreatic cancer, acute myeloid leukemia, and Kaposi's sarcoma.

[0015] Adenosine A2B Receptors are ubiquitous and regulate multiple biological activities. For example, adenosine binds to the A receptor on endothelial cells. 2B Adenosine binds to receptors, thereby stimulating angiogenesis. Adenosine also regulates the proliferation of smooth muscle cell populations in blood vessels. Adenosine binds to A receptors on mast cells. 2B Adenosine stimulates the A receptors in the intestine, thus modulating type I allergic reactions. 2B It also stimulates gastric secretory activity by binding to

[0016] Many of these biological effects of adenosine are necessary to maintain normal tissue homeostasis under several physiological changes, and it would be desirable to modulate their effects. 2B Receptor binding stimulates angiogenesis by promoting endothelial cell proliferation. Such activity is necessary for wound healing, but endothelial cell hyperproliferation contributes to diabetic retinopathy. Unwanted vascular proliferation also occurs in neoplasia. Therefore, adenosine and endothelial A 2B Inhibition of receptor binding reduces or prevents hypervascularization, thus preventing retinopathy and inhibiting tumor formation.

[0017] A 2B The receptor is found in the colon on the basolateral domain of intestinal epithelial cells and, when acted upon by an appropriate ligand, acts to increase chloride secretion, thus causing diarrhea, a common and potentially fatal complication of infectious diseases such as cholera and typhoid. 2B Antagonists can be used to block chloride secretion in the intestine and are therefore useful in treating inflammatory gastrointestinal disorders, including diarrhea. 2B Another adverse biological effect of adenosine acting at its receptors is the overstimulation of the cytokine brain IL-6, which is associated with dementia and Alzheimer's disease.

[0018] Therefore, A 2A / A 2B Shows complete or partial selectivity for the receptor, A 2A / A 2BPotent A receptor modulators useful in the treatment of various pathologies, such as cancer. 2A / A 2B Antagonists (i.e., A 2A / A 2B It would be desirable to provide compounds that inhibit adenosine receptors. [Prior art documents] [Patent documents]

[0019] [Patent Document 1] International Publication No. 02 / 055083 [Patent Document 2] International Publication No. 05 / 044245 [Patent Document 3] International Publication No. 06 / 132275 [Patent Document 4] U.S. Patent Application Publication No. 2007037033 [Patent Document 5] International Publication No. 01 / 058241 [Patent Document 6] International Publication No. 06 / 009698 [Patent Document 7] International Publication No. 2012038980 [Patent Document 8] International Publication No. 2010103547 [Patent Document 9] International Publication No. 2012035548 [Non-patent literature]

[0020] [Non-Patent Document 1] Trends Pharmacol. Sci., 1997, vol. 18, pp. 338-344 [Non-patent document 2] Life Sci., 1994, vol. 55, pp. 61-65 [Non-patent document 3] Arthritis & Rheumatism, Vol. 54(No. 8), pp. 2632-2642, 2006 [Non-licensed Document 4] Pharmacol. Ther., 2005, Vol. 105, p. 267 [Non-licensed Document 5] J. Mol. Neurosci., 2005, Vol. 26, p. 209 [Non-licensed Document 6] Trends in Pharmacological Sciences, 2003, Volume 24, Page 8 [Non-licensed Document 7] Cancer Immunol Res., 2015, Vol. 3, pp. 506-517 [Non-licensed Document 8] Feoktistov, I. Pharmacol. Rev., 1997, Vol. 49, pp. 381-402 [Non-licensed Document 9] Pharmacological Reviews, 2003, Volume 49, No. 4 [Non-licensed Document 10] Pulmonary Pharmacology & Therapeutics, 1999, Volume 12, pp. 111-114 [Non-licensed Document 11] Curr. Drug Targets, 2006, volume 7, pages 699~706 [Non-licensed Document 12] Am. J. Resper. Cell. Mol. Biol., 2005, Volume 32, Page 228 [Non-licensed Document 13] Circ. Res., 2002, Volume 90, pp. 531-538 [Non-licensed Document 14] Am.J. Physiol. Heart Circ. Physiol., 2004, Vol. 287, pp. H2478-H2486 [Non-licensed Document 15] Am. J. Respir. Cell Mol. Biol., 2008, Vol. 39, pp. 190-197 [Non-licensed Document 16] The Journal of Pharmacol. and Exp. Ther., 2004, Vol. 308, pp. 358-366 [Non-Patent Document 17] J Pharm. Pharmacol., December 2006; Volume 58 (Issue 12): Pages 1639-45 Summary of the Invention [Means for solving the problem]

[0021] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising a compound of Formula I and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition.

[0022] [ka]

[0023] [In the formula, --- represents a single or double bond, X is O, S or NR a is selected from Y1 is selected from N or CH; Y2 is NR 5 , O or CR 5 R 6 is selected from Y3 is selected from N, CH, CH2, C(=O), or C(=S); Y4 is selected from N, C, or CH; R 1 and R 2 are independently selected from hydrogen or alkyl; R 3 is -AZBQ, where A is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a)-, or -C(O), wherein alkylene, alkenylene, and alkynylene are groups selected from alkylene, alkenylene, and alkynylene, optionally substituted by groups such as -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyano, halogen, haloalkyl, perhaloalkyl, alkoxyalkoxy, alkyl, or cycloalkyl; Z is absent or selected from cycloalkyl or heterocyclyl, where cycloalkyl and heterocyclyl are unsubstituted or selected from alkyl, alkenyl, alkynyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , aminocarbonyl, alkoxycarbonylamino, halogen, haloalkyl, perhaloalkyl, azido, cyano, keto, thiocarbonyl, -SO3H, aminocarbonylamino, nitro, -S(O)2NR a R a , -NR b S(O)2R b or -S(O) p R c and is independently substituted with 1, 2, or 3 substituents independently selected from: B is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a)-, or -C(O), wherein the alkylene, alkenylene, and alkynylene are optionally substituted with hydroxy, amino, aminoalkyl, cyano, halogen, haloalkyl, perhaloalkyl, carboxy, carboxyalkyl, alkoxy, hydroxyalkyl, alkoxyalkyl, alkoxyalkoxy, or alkyl; Q is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, where alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, halogen, haloalkyl, perhaloalkyl, azido, cyano, nitro, keto, thiocarbonyl, cyanoalkyl, cyanoalkylcarbonyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , -(CR d R e ) n SR 7 , -(CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , -(CR d R e ) n C(O)NR 8 R 9 , -(CR d R e ) n NR 8 C(O)OR 7 , -(CR d R e )n NR 8 C(O)NR 8 R 9 , -NR b S(O)2R b , -S(O) p R c , -SO3H, -S(O)2NR a R a , cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; each substituent is unsubstituted or substituted with one, two, or three substituents independently selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, amino, substituted amino, cyano, or -S(O) p R c and is substituted with 1, 2, or 3 substituents independently selected from R 4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, where alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9, aminocarbonyl, alkoxycarbonylamino, aminocarbonylamino, azido, cyano, halogen, haloalkyl, perhaloalkyl, keto, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R c , thiocarbonyl, —SO3H, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; R 5 and R 6 are independently hydrogen, hydroxy, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyanoalkyl, haloalkyl, alkoxyalkoxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl; R 7 is hydrogen, alkyl, halogen, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n COOR 7 , -(CR e R e ) n C(O)R 7 , carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; R8 and R 9 are independently hydrogen, alkyl, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl; or R 8 and R 9 together form a monocyclic or bicyclic ring system which is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N or S, said ring system being free of halo, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR d R e ) n OR 7 , -(CR d R e ) n SR 7 , -(CR d R e ) n NR 8 R 9 , oxo, alkylsulfonyl, -(CR d R e ) n COOR 7 , -(CR d R e ) n C(O)NR 8 R 9 , cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; R a is selected from hydrogen or alkyl; R bare each independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R d and R e are independently hydrogen, -OR 7 , selected from the group consisting of halogen, haloalkyl, perhaloalkyl, and alkyl; n is 0, 1, 2, 3 or 4; p is 0, 1 or 2].

[0024] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising a compound of formula II and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition.

[0025] [ka]

[0026] [In the formula, Y is selected from N or CR, and R is selected from H, hydroxy, alkoxy, alkyl, or aryl; R 1 is a group in which one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a)-, or -C(O), with the proviso that the heteroatom is not adjacent to the N in the ring and p is selected from 0, 1, or 2, where alkyl, alkenyl, and alkynyl are unsubstituted or are selected from alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SOH, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, -S(O)NR a R a , -NR a S(O)2R a , or -S(O) p R a are independently substituted with R 2 is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, haloalkyl, haloalkyloxy, alkoxy, -NR b R b , -S(O) p R b , cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy; wherein alkyl, alkenyl, alkynyl, alkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, and R bis unsubstituted or alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO3H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R 3is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SOH, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from X is optionally substituted arylene or optionally substituted heteroarylene; A is a bond, 1 to 4 methylene groups are O, -S(O) p -, -N(R b)-, or —C(O)—, where alkylene, alkenylene, and alkynylene are unsubstituted or selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, —SOH, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl, or heteroaryl, wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R a are independently selected from hydrogen or alkyl; R b is independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R cis selected from hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl; R d is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; p is 0, 1 or 2].

[0027] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising compounds of formula III or IV and pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of medicaments for the treatment of conditions or disorders ameliorated by receptor inhibition.

[0028] [ka]

[0029] [In the formula, R 1 is a group in which one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), with the proviso that the heteroatom is not adjacent to the N in the ring and p is selected from 0, 1 or 2, wherein alkyl is unsubstituted or substituted with alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -aminocarbonylamino, hydroxyamino, alkoxyamino; R 2 is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, haloalkyl, haloalkyloxy, alkoxy, -NR b Rb , -S(O) p R b , cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy; wherein alkyl, alkenyl, alkynyl, alkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, and R b is unsubstituted or alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO3H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R' and R" are independently selected from hydrogen or alkyl; R' and R" together can represent O or a saturated or partially unsaturated lower cycloalkyl ring system; R 3 is alkyl, aryl, -C(O)R 4 and -P(O)(OR 5 )2, R 4 is alkyl, alkoxy, aryl, heteroaryl, heterocyclyl, or -NR 6 R 7 is selected from R 5 is selected from hydrogen, alkyl, aryl, arylalkyl, —CHOC(O)alkyl, or —CHOC(O)Oalkyl, or two R 5 the groups taken together form a 5- or 6-membered ring system which is saturated or partially unsaturated and optionally substituted with 1 to 4 substituents independently selected from halo, alkyl, aryl, or heteroaryl; R 6 and R 7 is independently selected from the group consisting of hydrogen, alkyl, heterocyclyl, and heterocyclylalkyl; or R 6 and R 7 together form a monocyclic ring system that is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N, or S, wherein the ring system is not substituted with a halo, alkyl, alkoxy, or -NR 8 R 9 and optionally substituted with 1 to 4 substituents independently selected from R 4 , R 5 , R 6 and R 7 is hydroxyl, halogen, alkyl, alkoxy, haloalkyl, -NR 8 R 9 , -C(O)OR 10 , -OC(O)R 10 or -NC(O)R 10 and optionally substituted with 1 to 4 substituents independently selected from R 8 and R9 are independently selected from the group consisting of hydrogen and alkyl; R 10 is selected from hydrogen, hydroxy, halogen, amino, substituted amino, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, carboxy, carboxyalkyl, aminocarbonyl, aryl, or arylalkyl; X is optionally substituted arylene or optionally substituted heteroarylene; A is a bond or 1 to 4 methylene groups are O, -S(O) p -, -N(R b )-, or -C(O)-, where alkylene is unsubstituted or is selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SO3H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl, or heteroaryl, wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from D is -O-, -S(O)p-, or -N(R a )-selected from R a is hydrogen or alkyl, R bis selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl; R d is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; p is 0, 1 or 2; t is 1 or 2].

[0030] In an embodiment of the present disclosure, A 2A / A 2B A method of using a pharmaceutical composition of the present disclosure comprising a compound selected from the compounds of Formula I, Formula II, Formula III, or Formula IV, and pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in the treatment of a disease or condition in a mammal amenable to treatment with a receptor antagonist, is provided, comprising the step of administering a therapeutically effective amount of the pharmaceutical composition of the present disclosure to a mammal in need thereof.

[0031] In an embodiment of the present disclosure, A 2A / A 2B A method of treating a disorder or condition ameliorated by antagonizing a receptor is provided, comprising administering to a patient in need of such treatment an effective amount of a pharmaceutical composition of the present disclosure comprising a compound selected from a compound of Formula I, Formula II, Formula III, or Formula IV, and pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof.

[0032] In an aspect of the present disclosure, there is provided a use of a pharmaceutical composition of the present disclosure comprising a compound selected from the compounds of Formula I, Formula II, Formula III, or Formula IV and their pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the preparation of a medicament for the treatment of a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0033] These and other features, aspects, and advantages of the present subject matter will become better understood with reference to the following description. This summary is provided to present selected concepts in a simplified form. It is not intended to identify key features or essential features of the disclosure, nor is it intended to limit the scope of the present subject matter. DETAILED DESCRIPTION OF THE INVENTION

[0034] Those skilled in the art will recognize that the present disclosure is susceptible to variations and modifications other than those specifically described. The present disclosure should be understood to include all such variations and modifications. The present disclosure includes all such steps, features, compositions, and compounds referred to or indicated herein, individually or collectively, and any and all combinations of any or more of such steps or features.

[0035] definition For convenience, before further describing this disclosure, some terms used in the specification and examples are collected here. These definitions should be read in light of the remainder of the disclosure and understood as by one of ordinary skill in the art. The terms used herein have meanings that are recognized and known to those of ordinary skill in the art; however, for convenience and completeness, certain terms and their meanings are set forth below.

[0036] The articles "a", "an" and "the" are used to refer to one or to more than one (ie to at least one) of the grammatical object of the article.

[0037] Throughout the following description and claims, unless the context otherwise requires, the word "comprise" and variations such as "comprises" and "comprising" will be deemed to imply the inclusion of a specified integer or step or group of integers but not the exclusion of any other integer or step or group of integers or steps.

[0038] The term "including" is used to mean "including but not limited to." "Including" and "including but not limited to" are used interchangeably.

[0039] In the structural formulas depicted herein and throughout this disclosure, the following terms have the indicated meanings unless specifically stated otherwise.

[0040] The term "alkyl" refers to a monoradical branched or unbranched saturated hydrocarbon chain having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, preferably 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, and more preferably 1, 2, 3, 4, 5, or 6 carbon atoms. This term is exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-hexyl, n-decyl, tetradecyl, and the like.

[0041] The term "alkylene" refers to a diradical of a branched or unbranched saturated hydrocarbon chain having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, preferably 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, and more preferably 1, 2, 3, 4, 5, or 6 carbon atoms. This term is exemplified by groups such as methylene (-CH-), ethylene (-CHCH-), propylene isomers (e.g., -CHCHCH- and -CH(CH)CH-).

[0042] The term "substituted alkyl" or "substituted alkylene" refers to the following: 1) alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, heteroarylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, carboxyalkyl, -SO3H, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)2NR a R a , -NR a S(O)2R a and -S(O) p R b , where R a are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, and heterocyclyloxy; R bis hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl. Unless otherwise constrained by definition, all substituents are selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O). p R c [where R c is alkyl, aryl, or heteroaryl, and p is 0, 1, or 2; or 2) Oxygen, sulfur and NR d [where R d are selected from hydrogen, alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocyclyl, carbonylalkyl, carboxyester, carboxamido and sulfonyl, and all substituents are alkyl, alkoxy, halogen, CF3, amino, substituted amino, cyano, or -S(O) p R c [where R c is alkyl, aryl, or heteroaryl, and p is 0, 1, or 2; or 3) Alkyl or alkylene as defined above, having 1, 2, 3, 4 or 5 substituents as defined above, and interrupted by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms as defined above.

[0043] The term "alkenyl" refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group preferably having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, and even more preferably 2, 3, 4, 5, or 6 carbon atoms, and having 1, 2, 3, 4, 5, or 6 double bonds (vinyl), preferably 1 double bond. Preferred alkenyl groups include ethenyl or vinyl (-CH=CH), 1-propylene or allyl (-CHCH=CH), isopropylene (-C(CH)=CH), bicyclo[2.2.1]heptene, and the like.

[0044] The term "alkenylene" refers to a diradical of a branched or unbranched unsaturated hydrocarbon group preferably having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, and even more preferably 2, 3, 4, 5 or 6 carbon atoms, and having 1, 3, 4, 5 or 6 double bonds (vinyl), preferably 1 double bond.

[0045] The term "substituted alkenyl" includes alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, thiocarbonyl, carboxy, carboxyalkyl, -SO3H, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)2NR a R a , -NR a S(O)2R a and -S(O) p R b [where R aare each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, and heterocyclyloxy; R b refers to an alkenyl group as defined above having 1, 2, 3, 4 or 5 substituents, preferably 1, 2 or 3 substituents, selected from the group consisting of: alkyl, aryl, heteroaryl or heterocyclyl, and p is 0, 1 or 2. Unless otherwise constrained by definition, all substituents are selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O). p R c [where R c is alkyl, aryl, or heteroaryl; and p is 0, 1, or 2.

[0046] The term "alkynyl" refers to a monoradical of an unsaturated hydrocarbon preferably having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, and even more preferably 2, 3, 4, 5, or 6 carbon atoms, and having 1, 2, 3, 4, 5, or 6 sites of acetylenic (triple bond) unsaturation, preferably one triple bond. Preferred alkynyl groups include ethynyl, (-C≡CH), propargyl (or prop-1-yn-3-yl, -CHC≡CH), homopropargyl (or but-1-yn-4-yl, -CHCHC≡CH), and the like.

[0047] The term "alkynylene" refers to a diradical of a branched or unbranched unsaturated hydrocarbon group preferably having 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, more preferably 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, and even more preferably 2, 3, 4, 5, or 6 carbon atoms, and having 1, 3, 4, 5, or 6 sites of acetylenic (triple bond) unsaturation, preferably 1 triple bond.

[0048] The term "substituted alkynyl" includes alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, -SOH, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)NR a R a , -NR a S(O)2R a and -S(O) p R b , where R a are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, and heterocyclyloxy; R b refers to an alkynyl group as defined above bearing 1, 2, 3, 4 or 5 substituents, preferably 1, 2 or 3 substituents, selected from the group consisting of: alkyl, aryl, heteroaryl or heterocyclyl, and p is 0, 1 or 2. Unless otherwise constrained by definition, all substituents are selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O). p R c [where R cis alkyl, aryl, or heteroaryl; and p is 0, 1, or 2.

[0049] The term "cycloalkyl" refers to a carbocyclic group of 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings, which may be partially unsaturated. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclooctyl, and the like, or multiple ring structures such as adamantanyl, bicyclo[2.2.1]heptane, 1,3,3-trimethylbicyclo[2.2.1]hept-2-yl, (2,3,3-trimethylbicyclo[2.2.1]hept-2-yl), and the like, or carbocyclic groups fused to an aryl group, such as indan.

[0050] The term "substituted cycloalkyl" includes alkyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -C(O)R, and -S(O)R. p R b wherein R is hydrogen, hydroxyl, alkoxy, alkyl, cycloalkyl, heterocyclyloxy, and R b refers to a cycloalkyl group having 1, 2, 3, 4 or 5 substituents, preferably 1, 2 or 3 substituents, selected from the group consisting of: alkyl, aryl, heteroaryl or heterocyclyl, and p is 0, 1 or 2. Unless otherwise constrained by definition, all substituents are alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O) p R c[where R c is alkyl, aryl, or heteroaryl; and p is 0, 1, or 2.

[0051] "Halo" or "halogen", alone or in combination with any other term, means halogens such as chloro (Cl), fluoro (F), bromo (Br) and iodo (I).

[0052] "Haloalkyl" refers to a straight- or branched-chain haloalkyl group having 1 to 6 carbon atoms. The alkyl group can be partially or fully halogenated. Representative examples of haloalkyl groups include, but are not limited to, fluoromethyl, chloromethyl, bromomethyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, and the like.

[0053] The term "alkoxy" refers to the group R'''-O-, where R''' is optionally substituted alkyl or optionally substituted cycloalkyl, or optionally substituted alkenyl or optionally substituted alkynyl, or optionally substituted cycloalkenyl, where alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl are as defined herein. Representative examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, trifluoromethoxy, and the like.

[0054] The term "aminocarbonyl" refers to the group -C(O)NR'R', where each R' is independently hydrogen, alkyl, aryl, heteroaryl, heterocyclyl, or both R' groups taken together form a heterocyclic group (e.g., morpholino). Unless otherwise constrained by definition, all substituents are alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano, and -S(O) p R c [where R c is alkyl, aryl, or heteroaryl, and p is 0, 1, or 2.

[0055] The term "acylamino" refers to the group -NR"C(O)R" where each R" is independently hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl. Unless otherwise constrained by definition, all substituents are alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O) p R c [where R c is alkyl, aryl, or heteroaryl, and p is 0, 1, or 2.

[0056] The term "acyloxy" refers to the groups -OC(O)-alkyl, -OC(O)-cycloalkyl, -OC(O)-aryl, -OC(O)-heteroaryl, and -OC(O)-heterocyclyl. Unless otherwise constrained by definition, all substituents are alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, or -S(O) p R c [where R cis alkyl, aryl, or heteroaryl, and p is 0, 1, or 2.

[0057] The term "alkoxyalkyl" refers to an alkyl group, as defined above, in which at least one of the alkyl group's hydrogen atoms has been replaced by an alkoxy group, as defined above. Representative examples of alkoxyalkyl groups include, but are not limited to, methoxymethyl, methoxyethyl, ethoxymethyl, and the like.

[0058] The term "aryloxyalkyl" refers to the group -alkyl-O-aryl. Representative examples of aryloxyalkyl include, but are not limited to, phenoxymethyl, naphthyloxymethyl, phenoxyethyl, naphthyloxyethyl, and the like.

[0059] The term "dialkylamino" refers to an amino group having two of the same or different straight or branched chain alkyl groups, each having 1 to 6 carbon atoms, attached thereto. Representative examples of dialkylamino include, but are not limited to, dimethylamino, diethylamino, methylethylamino, dipropylamino, dibutylamino, and the like.

[0060] The term "cycloalkylalkyl" refers to an alkyl group, as defined above, substituted by a cycloalkyl group, as defined above. Representative examples of cycloalkylalkyl include, but are not limited to, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 1-cyclopentylethyl, 1-cyclohexylethyl, 2-cyclopentylethyl, 2-cyclohexylethyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylbutyl, and the like.

[0061] The term "aminoalkyl" refers to an amino group attached to a (C1-6)alkylene, as defined herein. Representative examples of aminoalkyl include, but are not limited to, aminomethyl, aminoethyl, 1-aminopropyl, 2-aminopropyl, and the like. The amino moiety of aminoalkyl can be substituted once or twice with alkyl to form alkylaminoalkyl and dialkylaminoalkyl, respectively. Representative examples of alkylaminoalkyl include, but are not limited to, methylaminomethyl, methylaminoethyl, methylaminopropyl, ethylaminoethyl, and the like. Representative examples of dialkylaminoalkyl include, but are not limited to, dimethylaminomethyl, dimethylaminoethyl, dimethylaminopropyl, N-methyl-N-ethylaminoethyl, and the like.

[0062] The term "aryl" refers to an aromatic carbocyclic group of 6 to 20 carbon atoms having a single ring (e.g., phenyl) or multiple rings (e.g., biphenyl), or multiple condensed rings (e.g., naphthyl or anthranyl). Preferred aryls include phenyl, naphthyl, and the like.

[0063] The term "arylene" refers to the diradical of an aryl group, as defined above. This term is exemplified by groups such as 1,4-phenylene, 1,3-phenylene, 1,2-phenylene, 1,4'-biphenylene, and the like.

[0064] Unless otherwise restricted, an aryl or arylene group can be alkyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, carboxy, carboxyalkyl, —SOH, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, —S(O)NR a R a , -NR a S(O)2Ra and -S(O) p R b [where R a are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R b is hydrogen, alkyl, aryl, heterocyclyl, or heteroaryl, and p is 0, 1, or 2. Unless otherwise constrained by definition, all substituents are selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O). p R c [where R c is hydrogen, alkyl, aryl, or heteroaryl; and p is 0, 1, or 2.

[0065] The term "arylalkyl" refers to an aryl group covalently linked to an alkylene group, where aryl and alkylene are as defined herein.

[0066] The term "optionally substituted arylalkyl" refers to an optionally substituted aryl group covalently attached to an optionally substituted alkylene group. Such arylalkyl groups are exemplified by benzyl, phenethyl, naphthylmethyl, and the like.

[0067] The term "aryloxy" refers to the group --O-aryl, where aryl is as defined above, including optionally substituted aryl groups, also defined above.

[0068] The term "arylthio" refers to the group --S-aryl, where aryl is as defined herein, including optionally substituted aryl, also defined above.

[0069] The term "substituted amino" refers to the group -NR'R', where each R' is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, carboxyalkyl, alkoxycarbonyl, aryl, heteroaryl, and heterocyclyl. Unless otherwise constrained by definition, all substituents include alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano, and -S(O) p R c [where R c is alkyl, aryl, or heteroaryl; and p is 0, 1, or 2.

[0070] The term "carboxyalkyl" refers to the group -alkylene-C(O)OH.

[0071] The term "alkylcarboxyalkyl" refers to -alkylene-C(O)OR d refers to the group, where R d is alkyl, cycloalkyl, where alkyl and cycloalkyl are as defined herein, and is alkyl, halogen, CF3, amino, substituted amino, cyano, or -S(O) p R c [where R c is alkyl, aryl, or heteroaryl, and p is 0, 1, or 2.

[0072] The term "heteroaryl" refers to an aromatic cyclic group having in at least one ring 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 carbon atoms and 1, 2, 3, or 4 heteroatoms selected from oxygen, nitrogen, and sulfur. Such heteroaryl groups can have a single ring (e.g., pyridyl or furyl) or multiple condensed rings (e.g., indolizinyl, benzothiazolyl, or benzothienyl). Examples of heteroaryls include, but are not limited to, [1,2,4]oxadiazole, [1,3,4]oxadiazole, [1,2,4]thiadiazole, [1,3,4]thiadiazole, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine, furan, thiophene, oxazole, thiazole, triazole, triazine, and the like.

[0073] The term "heteroarylene" refers to a diradical of a heteroaryl group as defined above.

[0074] Unless otherwise restricted, a heteroaryl or heteroarylene group may be any of the following: alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, thiocarbonyl, carboxy, carboxyalkyl, —SOH, aryl, aryloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, —S(O)NR a R a , -NR a S(O)2R a and -S(O) p Rb , where R a are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R b is hydrogen, alkyl, aryl, heterocyclyl, or heteroaryl, and p is 0, 1, or 2. Unless otherwise constrained by definition, all substituents are selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O). n R c [where R c is alkyl, aryl, or heteroaryl, and n is 0, 1, or 2.

[0075] The term "heteroarylalkyl" refers to a heteroaryl group covalently linked to an alkylene group, where heteroaryl and alkylene are as defined herein.

[0076] The term "optionally substituted heteroarylalkyl" refers to an optionally substituted heteroaryl group covalently attached to an optionally substituted alkylene group. Such heteroarylalkyl groups are exemplified by 3-pyridylmethyl, quinolin-8-ylethyl, 4-methoxythiazol-2-ylpropyl, and the like.

[0077] The term "heterocyclyl" refers to a saturated or partially unsaturated group having a single ring or multiple condensed rings, containing 1 to 40 carbon atoms and 1 to 10, preferably 1, 2, 3, or 4, heteroatoms selected from nitrogen, sulfur, phosphorus, and / or oxygen. Heterocyclic groups can have a single ring or multiple condensed rings, and examples include tetrahydrofuranyl, morpholinyl, piperidinyl, piperazinyl, dihydropyridinyl, tetrahydroquinolinyl, and the like. Unless otherwise constrained by the definition of a heterocyclic substituent, such heterocyclic groups are defined as alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, -C(O)R, where R is hydrogen, hydroxyl, alkoxy, alkyl and cycloalkyl, thiocarbonyl, carboxy, carboxyalkyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, and -S(O)R. p R b [where R b is hydrogen, alkyl, aryl, heterocyclyl, or heteroaryl, and p is 0, 1, or 2. Unless otherwise constrained by definition, all substituents are selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF, amino, substituted amino, cyano, and -S(O)R. c [where R c is alkyl, aryl, or heteroaryl, and n is 0, 1, or 2.

[0078] The term "heterocyclylalkyl" refers to a heterocyclyl group covalently linked to an alkylene group, where heterocyclyl and alkylene are defined herein.

[0079] The term "optionally substituted heterocyclylalkyl" refers to an optionally substituted heterocyclyl group covalently attached to an optionally substituted alkylene group.

[0080] The term "heteroaryloxy" refers to the group --O-heteroaryl.

[0081] The term "thiol" refers to the group --SH.

[0082] The term "substituted alkylthio" refers to the group --S-substituted alkyl.

[0083] The term "heteroarylthio" refers to the group --S-heteroaryl, where the heteroaryl group is as defined above, including optionally substituted heteroaryl groups, also defined above.

[0084] The term "sulfoxide" refers to the group -S(O).

[0085] The term "substituted sulfoxide" refers to the group --S(O)R, where R is substituted alkyl, substituted aryl, or substituted heteroaryl as defined above.

[0086] The term "sulfone" refers to the group -S(O)R, where R is alkyl, aryl, or heteroaryl.

[0087] The term "substituted sulfone" refers to the group -S(O)2R, where R is alkyl, aryl, or heteroaryl.

[0088] "A 2AThe term "disorder or condition ameliorated by receptor inhibition" will be understood by those skilled in the art to include cancers such as prostate cancer, colon cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, particularly breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, and more particularly lung cancer (e.g., Lewis lung carcinoma).

[0089] The compounds of the present disclosure may have the ability to crystallize in more than one form, a property known as crystalline polymorphism, and all such crystalline polymorphs ("polymorphs") are encompassed within the scope of the present invention. Crystalline polymorphism generally occurs as a response to changes in temperature or pressure, or both, and may also result from differences in the crystallization process. Polymorphs can be distinguished by various physical properties, and typically, the X-ray diffraction patterns, solubility behavior, and melting point of the compound are used to distinguish polymorphs.

[0090] The compounds described herein may contain one or more chiral centers and / or double bonds and, therefore, may exist as "stereoisomers," such as double bond isomers (i.e., "geometric isomers"), positional isomers, enantiomers, or diastereomers. Accordingly, the chemical structures depicted herein encompass all possible enantiomers and stereoisomers of the depicted or identified compounds, including stereomerically pure (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure) forms and enantiomeric and stereoisomeric mixtures. Enantiomeric and stereoisomeric mixtures can be resolved into their component enantiomers or stereoisomers using separation or chiral synthesis techniques well known to those skilled in the art. The compounds may also exist in several tautomeric forms, including enol forms, keto forms, and mixtures thereof.

[0091] Thus, the chemical structures depicted herein encompass all possible tautomeric forms of the compounds shown or identified.

[0092] Compounds can exist in non-solvated forms as well as solvated forms, including hydrated forms, and N-oxides. Generally, compounds can be hydrated, solvated, or N-oxides. Some compounds can exist in multiple crystalline or amorphous forms. Compound congeners, analogs, hydrolysis products, metabolites, and precursors or prodrugs are also contemplated within the scope of the present invention. Generally, unless otherwise indicated, all physical forms are equivalent for the uses contemplated herein and are intended to be within the scope of the present invention.

[0093] The term "prodrug" refers to a derivative of a drug molecule, e.g., an ester, carbonate, carbamate, urea, amide, or phosphate, that requires transformation within the body to liberate the active drug. Prodrugs are often, but not necessarily, pharmacologically inactive until converted to the parent drug. Prodrugs can be obtained by attaching a promoiety (as defined herein) to the drug, typically via a functional group.

[0094] The term "therapeutically effective amount" means an amount of a compound or composition sufficient to significantly and positively modify the symptoms and / or condition to be treated (e.g., provide a positive clinical response). The effective amount of active ingredient used in a pharmaceutical composition will vary depending on the particular condition being treated, the severity of the condition, the duration of treatment, the nature of any concurrent therapy, the particular active ingredient being used, the particular pharmaceutically acceptable excipients / carriers employed, the route of administration, and similar factors within the knowledge and expertise of the attending physician.

[0095] The term "promoiety" refers to a group that is attached to a drug, typically a functional group of the drug, via a bond that is cleavable under specified conditions of use. The bond between the drug and the promoiety can be cleaved by enzymatic or non-enzymatic means. Under conditions of use, for example, after administration to a patient, the bond between the drug and the promoiety can be cleaved to liberate the parent drug. Cleavage of the promoiety can proceed spontaneously, such as via a hydrolysis reaction, or can be catalyzed or induced by another agent, such as an enzyme, light, acid, or a change in or exposure to a physical or environmental parameter, such as a change in temperature, pH, etc. The agent can be endogenous to the conditions of use, such as an enzyme present in the systemic circulation to which the prodrug is administered or the acidic conditions of the stomach, or the agent can be supplied exogenously.

[0096] The phrase "pharmaceutically acceptable excipient" refers to a compound or composition that is physiologically tolerable and typically does not produce allergic or similar adverse reactions, including, but not limited to, gastric upset or dizziness, when administered to a mammal.

[0097] The term "pharmaceutically acceptable salt" includes salts with pharmaceutically acceptable acids or bases. Pharmaceutically acceptable acids include both inorganic acids, such as hydrochloric acid, sulfuric acid, phosphoric acid, diphosphoric acid, hydrobromic acid, hydroiodic acid, and nitric acid, and organic acids, such as citric acid, fumaric acid, maleic acid, malic acid, mandelic acid, ascorbic acid, oxalic acid, succinic acid, tartaric acid, benzoic acid, acetic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, or p-toluenesulfonic acid. Pharmaceutically acceptable bases include alkali metal (e.g., sodium or potassium) and alkaline earth metal (e.g., calcium or magnesium) hydroxides, and organic bases, such as alkylamines, arylalkylamines, and heterocyclic amines.

[0098] Other preferred salts according to the present invention are quaternary ammonium compounds in which the equivalent of an anion (X-) is related to the positive charge of the N atom. X- can be an anion of various mineral acids, such as chloride, bromide, iodide, sulfate, nitrate, phosphate, or an anion of organic acids, such as acetate, maleate, fumarate, citrate, oxalate, succinate, tartrate, maleate, mandelate, trifluoroacetate, methanesulfonate, and p-toluenesulfonate. X- is preferably an anion selected from chloride, bromide, iodide, sulfate, nitrate, acetate, maleate, oxalate, succinate, or trifluoroacetate. More preferably, X- is chloride, bromide, trifluoroacetate, or methanesulfonate.

[0099] Additionally, the compounds of Formula I, Formula II, Formula III, or Formula IV can be derivatives, analogs, stereoisomers, diastereomers, geometric isomers, polymorphs, solvates, co-crystals, intermediates, hydrates, metabolites, prodrugs, or pharmaceutically acceptable salts and compositions thereof.

[0100] It will be understood that the family of compounds of Formula I, Formula II, Formula III, or Formula IV includes isomeric forms, including diastereomers, enantiomers, tautomers, and geometric isomers of "E" or "Z" configuration or mixtures of E and Z isomers. It will also be understood that some isomeric forms, such as diastereomers, enantiomers, and geometric isomers, can be separated by physical and / or chemical methods by one skilled in the art.

[0101] The compounds disclosed herein may exist as single stereoisomers, racemates, and / or mixtures of enantiomers and / or diastereomers, and all such single stereoisomers, racemates, and mixtures thereof are intended to be within the scope of the described subject matter.

[0102] Compounds disclosed herein include: 2 H(D), 3 H(T),11 C. 13 C. 14 C. 15 N, 18 F, 35 S, 36 Cl, and 125 Isotopically labeled compounds of the present disclosure include, but are not limited to, isotopes of hydrogen, carbon, oxygen, fluorine, chlorine, iodine, and sulfur that can be incorporated into the compounds, such as I. 3 H, 13 C. 14 Radioisotopes such as C can be used in metabolic studies, kinetic studies, and imaging techniques such as positron emission tomography used in understanding tissue distribution of drugs. Compounds of the present disclosure in which hydrogen is replaced with deuterium can improve the metabolic stability and pharmacokinetic properties of drugs, such as in vivo half-life.

[0103] Pharmaceutical compositions comprising compounds of Formula I, Formula II, Formula III, or Formula IV, and their analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof, may also be referred to as "compositions of the present disclosure."

[0104] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising a compound of Formula I and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition.

[0105] [ka]

[0106] [In the formula, --- represents a single or double bond, X is O, S or NR a is selected from Y1 is selected from N or CH; Y2 is NR 5 , O or CR 5 R 6 is selected from Y3 is selected from N, CH, CH2, C(=O), or C(=S); Y4 is selected from N, C, or CH; R 1 and R 2 are independently selected from hydrogen or alkyl; R 3 is -AZBQ, where A is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), wherein alkylene, alkenylene, and alkynylene are groups selected from alkylene, alkenylene, and alkynylene, optionally substituted by groups such as -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyano, halogen, haloalkyl, perhaloalkyl, alkoxyalkoxy, alkyl, or cycloalkyl; Z is absent or selected from cycloalkyl or heterocyclyl, where cycloalkyl and heterocyclyl are unsubstituted or selected from alkyl, alkenyl, alkynyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9, aminocarbonyl, alkoxycarbonylamino, halogen, haloalkyl, perhaloalkyl, azido, cyano, keto, thiocarbonyl, -SO3H, aminocarbonylamino, nitro, -S(O)2NR a R a , -NR b S(O)2R b or -S(O) p R c and is independently substituted with 1, 2, or 3 substituents independently selected from: B is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), wherein alkylene, alkenylene, and alkynylene are optionally substituted with hydroxy, amino, aminoalkyl, cyano, halogen, haloalkyl, perhaloalkyl, carboxy, carboxyalkyl, alkoxy, hydroxyalkyl, alkoxyalkyl, alkoxyalkoxy, or alkyl; Q is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, where alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, halogen, haloalkyl, perhaloalkyl, azido, cyano, nitro, keto, thiocarbonyl, cyanoalkyl, cyanoalkylcarbonyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , -(CR d R e ) n SR 7 , -(CR d Re ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , -(CR d R e ) n C(O)NR 8 R 9 , -(CR d R e ) n NR 8 C(O)OR 7 , -(CR d R e ) n NR 8 C(O)NR 8 R 9 , -NR b S(O)2R b , -S(O) p R c , -SO3H, -S(O)2NR a R a , cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; each substituent is unsubstituted or substituted with one, two, or three substituents independently selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, amino, substituted amino, cyano, or -S(O) p R c and is substituted with 1, 2, or 3 substituents independently selected from R 4is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, where alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , aminocarbonyl, alkoxycarbonylamino, aminocarbonylamino, azido, cyano, halogen, haloalkyl, perhaloalkyl, keto, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R c , thiocarbonyl, —SO3H, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; R 5 and R 6 are independently hydrogen, hydroxy, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9, cyanoalkyl, haloalkyl, alkoxyalkoxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl; R 7 is hydrogen, alkyl, halogen, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n COOR 7 , -(CR e R e ) n C(O)R 7 , carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; R 8 and R 9 are independently hydrogen, alkyl, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl; or R 8 and R 9 together form a monocyclic or bicyclic ring system which is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N or S, said ring system being free of halo, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR d R e ) n OR 7 , -(CR d R e ) n SR7 , -(CR d R e ) n NR 8 R 9 , oxo, alkylsulfonyl, -(CR d R e ) n COOR 7 , -(CR d R e ) n C(O)NR 8 R 9 , cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; R a is selected from hydrogen or alkyl; R b are each independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R d and R e are independently hydrogen, -OR 7 , selected from the group consisting of halogen, haloalkyl, perhaloalkyl, and alkyl; n is 0, 1, 2, 3 or 4; p is 0, 1 or 2].

[0107] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising a compound of Formula I and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. [In the formula, --- represents a double bond, X is O, S or NR a is selected from Y1 is selected from N or CH; Y2 is NR 5 or CR 5 R 6 is selected from Y3 is selected from N, CH or CH2; Y4 is selected from N or C; R 1 and R 2 are independently selected from hydrogen or alkyl; R 3 is -AZBQ, where A is absent or one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), wherein alkylene is -(CR d R e ) n OR 7 , cyano, halogen, haloalkyl, perhaloalkyl, alkyl, or cycloalkyl; Z is absent or is selected from cycloalkyl or heterocyclyl; wherein cycloalkyl and heterocyclyl are unsubstituted or are alkyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , aminocarbonyl, alkoxycarbonylamino, halogen, haloalkyl, perhaloalkyl, azido, cyano, halogen, keto, thiocarbonyl, -SO3H, aminocarbonylamino, nitro, -S(O)2NRa R a , -NR b S(O)2R b or -S(O) p R c and is independently substituted with 1, 2, or 3 substituents independently selected from B is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), wherein alkylene is optionally substituted with hydroxy, amino, aminoalkyl, cyano, halogen, haloalkyl, perhaloalkyl, carboxy, carboxyalkyl, alkoxy, hydroxyalkyl, alkoxyalkyl, alkoxyalkoxy, or alkyl; Q is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; wherein alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or selected from alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, haloalkyl, perhaloalkyl, azido, cyano, nitro, halogen, keto, thiocarbonyl, cyanoalkyl, cyanoalkylcarbonyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , -(CR d R e ) n SR 7 , -(CR d R e ) n COOR 7 , -(CR d R e ) n NR 8R 9 , -(CR d R e ) n C(O)NR 8 R 9 , -(CR d R e ) n NR 8 C(O)OR 7 , -(CR d R e ),NR 8 C(O)NR 8 R 9 , -NR b S(O)2R b , -S(O) p R c , -SO3H, -S(O)2NR a R a , cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; Each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, amino, substituted amino, cyano, or -S(O) p R c and is substituted with 1, 2, or 3 substituents independently selected from R 4 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl; wherein alkyl, cycloalkyl, cycloalkylalkyl, arylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl are unsubstituted or substituted with alkyl, acyl, -(CR d R e ) n OR7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , aminocarbonyl, alkoxycarbonylamino, aminocarbonylamino, azido, cyano, halogen, haloalkyl, perhaloalkyl, keto, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R c , thiocarbonyl, —SO3H, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; R 5 and R 6 are independently hydrogen, hydroxy, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyanoalkyl, haloalkyl, alkoxyalkoxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; R 7 is selected from hydrogen, alkyl, halogen, haloalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, or heterocyclylalkyl; R 8 and R 9are independently hydrogen, alkyl, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl; or R 8 and R 9 together form a monocyclic or bicyclic ring system which is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N or S, said ring system being selected from halo, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR d R e ) n OR 7 , -(CR d R e ) n SR 7 , -(CR d R e ) n NR 8 R 9 , oxo, alkylsulfonyl, -(CR d R e ) n COOR 7 , -(CR d R e ) n C(O)NR 8 R 9 , cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; R a is selected from hydrogen or alkyl; R bare each independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R d and R e are independently hydrogen, -OR 7 , selected from the group consisting of halogen, haloalkyl, perhaloalkyl, and alkyl; n is 0, 1, 2, 3 or 4; p is 0, 1 or 2].

[0108] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising a compound of Formula I and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. [In the formula, --- represents a double bond, X is selected from O or S; Y1 represents N; Y2 is NR 5 represents Y3 represents N; Y4 represents C; R 1 and R 2 are independently selected from hydrogen or alkyl; R 3 is -AZBQ, where A is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a )-, or —C(O), Z is absent or is heterocyclyl; wherein heterocyclyl is unsubstituted or is selected from alkyl, acyl, -(CR d R e ) n 0R 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , haloalkyl, perhaloalkyl, cyano, halogen, keto, thiocarbonyl, -SO3H, nitro, -S(O)2NR a R a , -NR b S(O)2R b or -S(O) p R c and is independently substituted with 1, 2, or 3 substituents independently selected from B is absent, or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a )-, or —C(O), Q is selected from hydrogen, alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; wherein alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl are unsubstituted or selected from alkyl, alkoxy, alkoxyalkyl, haloalkyl, perhaloalkyl, azido, cyano, nitro, halogen, keto, thiocarbonyl, cyanoalkyl, cyanoalkylcarbonyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , -(CR d R e ) n SR 7 , -(CR d R e) n COOR 7 , -(CR d R e ) n NR 8 R 9 , -(CR d R e ) n C(O)NR 8 R 9 , -(CR d R e ) n NR 8 C(O)OR 7 , -(CR d R e ) n NR 8 C(O)NR 8 R 9 , -NR b S(O)2R b , -S(O) p R c , -SO3H, -S(O)2NR a R a , cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; Each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, amino, substituted amino, cyano, or -S(O) p R c and is substituted with 1, 2, or 3 substituents independently selected from R 4 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl; wherein alkyl, cycloalkyl, cycloalkylalkyl, arylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl are unsubstituted or substituted with alkyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , aminocarbonyl, alkoxycarbonylamino, aminocarbonylamino, azido, cyano, halogen, haloalkyl, perhaloalkyl, keto, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R c , thiocarbonyl, —SO3H, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; R 5 and R 6 are independently hydrogen, hydroxy, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyanoalkyl, haloalkyl, alkoxyalkoxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl; R 7is selected from hydrogen, alkyl, halogen, haloalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, or heterocyclylalkyl; R 8 and R 9 are independently hydrogen, alkyl, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl; or R 8 and R 9 together form a monocyclic or bicyclic ring system which is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N or S, said ring system being selected from halo, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR d R e ) n OR 7 , -(CR d R e ) n SR 7 , -(CR d R e ) n NR 8 R 9 , oxo, alkylsulfonyl, -(CR d R e ) n COOR 7 , -(CR d R e ) n C(O)NR 8 R 9, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; R a is selected from hydrogen or alkyl; R b are each independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R d and R e are independently hydrogen, -OR 7 , halogen, haloalkyl, perhaloalkyl or alkyl; n is 0, 1, 2, 3 or 4; p is 0, 1 or 2].

[0109] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising a compound of Formula I and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. [In the formula, --- represents a double bond, X is selected from O or S; Y1 represents N; Y2 is NR 5 represents Y3 represents N; Y4 represents C; R 1 and R 2 are independently selected from hydrogen or alkyl; R3 is -AZBQ, where A is absent or one or more methylene groups are replaced by a heteroatom or -O- or -N(R a )-; and Z is absent or is heterocyclyl; wherein heterocyclyl is unsubstituted or is selected from alkyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , haloalkyl, perhaloalkyl, cyano, halogen, keto, or thiocarbonyl; B is absent or one or more methylene groups are replaced by a heteroatom or -O-, -N(R a )-, or —C(O), Q is selected from hydrogen, alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; wherein alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl are unsubstituted or selected from alkyl, alkoxy, alkoxyalkyl, haloalkyl, perhaloalkyl, cyano, halogen, keto, thiocarbonyl, cyanoalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , -(CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , -(CR d Re ) n C(O)NR 8 R 9 , -(CR d R e ) n NR 8 C(O)OR 7 , -S(O) p R c , -SO3H, -S(O)2NR a R a , cycloalkyl, cycloalkenyl, aryl, heterocyclyl, or heteroaryl; Each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, amino, substituted amino, cyano, or -S(O) p R c and is substituted with 1, 2, or 3 substituents independently selected from R 4 is selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl; wherein alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl are unsubstituted or are substituted with alkyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyano, halogen, haloalkyl, perhaloalkyl, nitro, -S(O)2NR b R b , -NR b S(O)2R b , -S(O) p R c, thiocarbonyl, —SO3H, cycloalkyl, aryl, heteroaryl, or heterocyclyl; R 5 is hydrogen, hydroxy, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n COOR 7 , alkoxyalkoxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; R 7 is selected from hydrogen, alkyl, halogen, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl; R 8 and R 9 are independently hydrogen, alkyl, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl; or R 8 and R 9 together form a monocyclic or bicyclic ring system which is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N or S, said ring system being free of halo, alkyl, nitro, cyano, -(CR d R e ) n OR 7 , -(CR d R e ) n NR 8 R 9, oxo, alkylsulfonyl, -(CR d R e ) n COOR 7 Or -(CR d R e ) n C(O)NR 8 R 9 and optionally further substituted with 1 to 4 substituents independently selected from R a is selected from hydrogen or alkyl; R b are each independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, or heterocyclylalkyl; R c is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R d and R e are independently hydrogen, -OR 7 , selected from the group consisting of halogen, haloalkyl, perhaloalkyl, and alkyl; n is 0, 1, 2, 3 or 4; p is 0, 1 or 2].

[0110] In an embodiment of the present disclosure, A 2A / A 2B and pharmaceutical compositions comprising a compound of Formula I and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. [In the formula, --- represents a double bond, X is selected from O or S; Y1 represents N; Y2 is NR 5 represents Y3 represents N; Y4 represents C; R 1 and R 2 are independently selected from hydrogen or alkyl; R 3 is -AZBQ, where A is absent or one or more methylene groups are replaced by a heteroatom or -O- or -N(R a )-; and Z is absent or is a heterocyclyl selected from dihydrofuranyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, dihydropyrrole, dihydropyranyl, tetrahydropyranyl, pyrazolidinyl, imidazolidinyl, dihydropyridinyl, tetrahydropyridinyl, piperidinyl, dihydropyrazinyl, tetrahydropyrazinyl, piperazinyl, or dihydropyridinyl; wherein heterocyclyl is unsubstituted or is selected from alkyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , haloalkyl, perhaloalkyl, cyano, or halogen; B is absent or one or more methylene groups are replaced by a heteroatom or -O-, -N(R a )-, or —C(O), Q is selected from hydrogen, alkyl, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyridinyl, tetrahydropyranyl, piperazinyl, benzodiaxolyl, tetrahydroquinolinyl, morpholinyl, tetrahydronaphthyridinyl, tetrahydrothienopyridinyl, furanyl, pyridinyl, pyrimidinyl, oxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, indolyl, quinolinyl, isoquinolinyl, or benzoxazolyl; wherein Q is unsubstituted or is alkyl, alkoxy, alkoxyalkyl, haloalkyl, perhaloalkyl, cyano, halogen, keto, thiocarbonyl, cyanoalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , -(CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , -(CR d R e ) n C(O)NR 8 R 9 , -(CR d R e ) n NR 8 C(O)OR 7 , -S(O) p R c , -SO3H, -S(O)2NR a R a , cycloalkyl, cycloalkenyl, aryl, heterocyclyl, or heteroaryl; Each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, amino, substituted amino, cyano, or -S(O) p R c and is substituted with 1, 2, or 3 substituents independently selected from R 4 is selected from the group consisting of hydrogen, alkyl, phenyl, naphthyl, furanyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, pyrazinyl, pyridinyl, and pyrimidinyl; where R 4 is unsubstituted, or alkyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , substituted with up to four substituents independently selected from cyano, halogen, haloalkyl, perhaloalkyl, or cycloalkyl; R 5 is hydrogen, hydroxy, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n COOR 7 , alkoxyalkoxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl; R 7 is selected from hydrogen, alkyl, halogen, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl; R 8 and R9 are independently hydrogen, alkyl, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl; or R 8 and R 9 together form a monocyclic or bicyclic ring system which is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N or S, said ring system being free of halo, alkyl, nitro, cyano, -(CR d R e ) n OR 7 , -(CR d R e ) n NR 8 R 9 , oxo, alkylsulfonyl, -(CR d R e ) n COOR 7 Or -(CR d R e ) n C(O)NR 8 R 9 and optionally further substituted with 1 to 4 substituents independently selected from R a is selected from hydrogen or alkyl; R in each occurrence b is independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, or heterocyclylalkyl; R c is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R d and R e are independently hydrogen, -OR 7 , selected from the group consisting of halogen, haloalkyl, perhaloalkyl, and alkyl; n is 0, 1, 2, 3 or 4; p is 0, 1 or 2].

[0111] In embodiments of the present disclosure, there is provided a pharmaceutical composition comprising a compound of Formula I as disclosed herein and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0112] In an embodiment of the present disclosure, A 2A / A 2B

[0013] Methods of using pharmaceutical compositions comprising compounds of Formula I, and pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, as disclosed herein, in the treatment of diseases or conditions in mammals amenable to treatment with a receptor antagonist, are provided, comprising administering to a mammal in need thereof a therapeutically effective amount of a pharmaceutical composition comprising compounds of Formula I, and pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof.

[0113] In an embodiment of the present disclosure, A 2A / A 2B A method of treating a disorder or condition ameliorated by antagonizing a receptor is provided, comprising administering to a patient in need of such treatment an effective amount of a pharmaceutical composition comprising a compound of Formula I disclosed herein, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof.

[0114] In an embodiment of the present disclosure, there is provided a use of a pharmaceutical composition comprising a compound of Formula I disclosed herein, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the preparation of a medicament for the treatment of a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0115] In embodiments of the disclosure, there is provided a pharmaceutical composition comprising a compound of Formula I as disclosed herein, pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in combination with at least one PD-L1 antibody for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0116] In embodiments of the disclosure, there is provided the use of a pharmaceutical composition comprising a compound of Formula I as disclosed herein, pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in combination with at least one PD-L1 antibody for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0117] In an embodiment of the present disclosure, there is provided a pharmaceutical composition comprising a compound of Formula I as disclosed herein, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, wherein the compound of Formula I is: 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (1), 5-amino-8-(2-furyl)-3-(2-hydroxyethyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (2), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (3), 5-amino-8-(2-furyl)-3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (4), 5-amino-8-(2-furyl)-1-methyl-3-(2-morpholinoethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (5), 5-amino-3-[2-[4-(2,4-difluorophenyl)-1-piperidyl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (6), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-(5-methyl-2-pyridyl)piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (7), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-(p-tolyl)piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (8), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-(3-methyl-2-oxo-butyl)piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (9), 5-amino-3-[2-[4-(2-fluoro-4-methoxy-phenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (10), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxy-1,1-dimethyl-ethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (11), 5-amino-8-(2-furyl)-3-[2-[4-(6-methoxy-3-pyridyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (12), 5-amino-3-[2-[4-[3-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (13), 5-amino-8-(2-furyl)-3-[2-[4-[4-(1-hydroxy-1-methyl-ethyl)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (14), 5-amino-3-[2-[4-(4-fluorophenyl)-4-hydroxy-1-piperidyl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (15), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxy-2-methyl-propoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (16), 5-amino-3-[2-[4-[4-(cyclopropoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (17), 5-amino-3-[2-[4-(4-fluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (18), 5-amino-8-(2-furyl)-3-[2-[4-hydroxy-4-(4-methoxyphenyl)-1-piperidyl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (19), 5-amino-3-[2-[4-[3,5-difluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (20), 5-amino-3-[2-[4-[2,5-difluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (21), 5-amino-3-[2-[4-(2,2-difluoro-1,3-benzodioxol-5-yl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (22), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]-3,3-dimethyl-piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (23), 5-amino-3-[2-(4-butylpiperazin-1-yl)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (24), 5-amino-8-(2-furyl)-3-[2-(4-hydroxy-4-methyl-1-piperidyl)ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (25), 5-amino-3-[2-[4-[4-[2-(cyclopropoxy)ethoxy]phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (26), 5-amino-8-(2-furyl)-3-[2-[4-[(4-methoxyphenyl)methyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (27), 5-amino-8-(2-furyl)-3-[2-[4-[[4-(2-methoxyethoxy)phenyl]methyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (28), 5-amino-8-(2-furyl)-3-[(4-methoxyphenyl)methyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (29), 5-amino-8-(2-furyl)-3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (30), 5-amino-8-(2-furyl)-3-[2-[4-[3-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (31), 5-amino-3-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (32), 4-[4-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3yl]ethyl]piperazin-1-yl]benzonitrile (33), 4-[4-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]piperazin-1-yl]-2-fluoro-benzonitrile (34), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (35), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-[4-(trifluoromethyl)thiazol-2-yl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (36), 5-amino-3-[2-[4-(cyclopropylmethyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (37), 5-amino-3-[2-(4-ethylpiperazin-1-yl)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (38), 4-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N,N-dimethyl-piperazine-1-sulfonamide (39), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-(4-tetrahydrofuran-3-yloxyphenyl)piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (40), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-(4-tetrahydropyran-4-yloxyphenyl)piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (41), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-[4-(tetrahydrofuran-2-ylmethoxy)phenyl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (42), 5-amino-8-(2-furyl)-1-methyl-3-[2-(3-methyl-7,8-dihydro-5H-1,6-naphthyridin-6-yl)ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (43), 5-amino-3-[2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (44), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]propyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (45), 5-amino-3-[2-[3-(4-fluorophenyl)-2,5-dihydropyrrol-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (46), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-(5-methyl-2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (47), 5-amino-8-(5-cyclopropyl-2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (48), 5-amino-3-[2-(2,4-difluoroanilino)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (49), 5-amino-3-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (50), 5-amino-8-(2-furyl)-3-[3-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]propyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (51), 5-amino-8-(2-furyl)-3-[2-[4-(4-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (52), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxy-1,1-dimethyl-ethyl)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (53), 5-amino-8-(2-furyl)-1-methyl-3-(2-piperazin-1-ylethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (54), 5-amino-8-(2-furyl)-3-[2-[4-(1H-indole-2-carbonyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (55), 5-amino-8-(2-furyl)-3-[2-(4-isopropoxyphenyl)ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (56), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (57), 5-amino-8-(2-furyl)-3-[2-(4-methoxyphenyl)ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (58), 5-amino-3-[2-[4-[4-(difluoromethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (59), 5-amino-8-(2-furyl)-1-methyl-3-[2-[4-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (60), 5-amino-3-[2-[4-[2-fluoro-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (61), 5-amino-3-[2-[4-(6-fluoro-2-methyl-1,3-benzoxazol-5-yl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (62), 5-amino-3-[2-[4-(cyclopropanecarbonyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (63), 5-amino-3-[2-[4-(2-cyclopropylacetyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (64), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-hydroxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (65), 5-amino-8-(2-furyl)-3-[2-[4-(4-hydroxyphenyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (66), 5-amino-1-(cyclopropylmethyl)-3-[2-[4-(4-ethoxyphenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (67), 5-amino-1-(cyclopropylmethyl)-3-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (68), 5-amino-1-(cyclopropylmethyl)-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (69), 5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (70), 5-amino-1-(cyclopropylmethyl)-3-[2-(4-fluorophenoxy)ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (71), 5-amino-8-(2-furyl)-1-methyl-3-[2-[2-oxo-5-(trifluoromethyl)-1-pyridyl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (72), 5-amino-3-[2-[4-(2,4-difluorophenyl)pyrazol-1-yl]ethyl]-1-ethyl-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (73), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]pyrazole-4-carboxylic acid (74), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]pyrazole-4-carboxylic acid (75), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-pyrazole-4-carboxamide (76), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N,N-diethyl-pyrazole-4-carboxamide (77), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-5-methyl-pyrazole-3-carboxamide (78), 2-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-5-methyl-pyrazole-3-carboxamide (79), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-methyl-pyrazole-3-carboxamide (80), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N,N-diethyl-pyrazole-4-carboxamide (81), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]pyrazole-4-carboxamide (82), 5-amino-8-(2-furyl)-3-[2-[4-[(3R)-3-hydroxypyrrolidine-1-carbonyl]pyrazol-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (83), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-methyl-pyrazole-4-carboxamide (84), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-pyrazole-3-carboxamide (85), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-pyrazole-4-carboxamide (86), 5-amino-8-(2-furyl)-3-[2-[4-(3-hydroxyazetidine-1-carbonyl)pyrazol-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (87), 5-amino-1-ethyl-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (88), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl]ethyl]-1-ethyl-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (89), 5-amino-1-ethyl-3-{2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-ethyl}-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-f]purin-2-one (90), 5-amino-1-ethyl-8-(2-furyl)-3-[2-(3-methyl-7,8-dihydro-5H-1,6-naphthyridin-6-yl)ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (91), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (92), 5-amino-3-{2-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-ethyl}-8-furan-2-yl-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-f]purin-2-one (93), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-(2-methoxyethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (94), 5-amino-3-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-(2-methoxyethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (95), 5-amino-3-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-(2-hydroxyethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (96), 5-amino-1-cyclopropyl-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (97), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (98), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (99), 5-amino-3-[2-[4-[3-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (100), 5-amino-3-[2-[4-(2-cyclopropylacetyl)piperazin-1-yl]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (101), 5-amino-3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (102), 5-amino-1-methyl-3-[2-[4-(p-tolyl)piperazin-1-yl]ethyl]-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (103), 5-amino-1-methyl-3-[2-(3-methyl-7,8-dihydro-5H-1,6-naphthyridin-6-yl)ethyl]-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (104), 4-[4-[2-(5-amino-1-methyl-2-oxo-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-3-yl)ethyl]piperazin-1-yl]benzonitrile (105), 5-amino-1-methyl-3-[2-[4-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]piperazin-1-yl]ethyl]-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (106), 5-amino-3-[2-[4-[4-(1-hydroxy-1-methyl-ethyl)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (107), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-2-one (108), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl]ethyl]-1-methyl-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-2-one (109), 4-[4-[2-[5-amino-1-methyl-2-oxo-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]piperazin-1-yl]benzonitrile (110), 5-amino-3-[2-[4-[4-(1-hydroxy-1-methyl-ethyl)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-2-one (111), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-pyrazin-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (112), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl]ethyl]-1-methyl-8-pyrazin-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (113), 5-amino-3-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-pyrazin-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (114), 5-amino-8-(2-furyl)-3-[[1-(4-methoxyphenyl)pyrrolidin-3-yl]methyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (115), 5-amino-8-(2-furyl)-3-[[1-[4-(2-methoxyethoxy)phenyl]pyrrolidin-3-yl]methyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one(hyl)}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (116), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purine-2-thione (117), 8-(2-Furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-5-(methylamino)-[1,2,4]triazolo[5,1-f]purin-2-one (118), 5-amino-3-{2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethyl}-8-isothiazol-5-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (119), 5-amino-8-isothiazol-5-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (120), 5-amino-3-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-isothiazol-5-yl-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (121), 5-amino-8-isoxazol-5-yl-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (122), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-8-oxazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (123), 5-amino-3-{2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-1-methyl-8-prop-1-ynyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (124), 5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-8-prop-1-ynyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (125), 5-amino-3-{2-[4-(4-fluoro-benzoyl)-piperazin-1-yl]-ethyl}-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (126), 5-amino-3-(2-dimethylamino-ethyl)-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (127), 5-amino-8-furan-2-yl-3-[3-(4-methoxy-phenyl)-propyl]-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (128), 5-amino-8-furan-2-yl-1-methyl-3-(2-pyrazol-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (129), 5-amino-8-furan-2-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-pyrazol-1-yl}-ethyl)-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (130), 5-amino-8-furan-2-yl-3-{2-[3-(4-methoxy-phenyl)-pyrrol-1-yl]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (131), 5-amino-8-furan-2-yl-3-{2-[4-(4-methoxy-phenyl)-imidazol-1-yl]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (132), 5-amino-8-furan-2-yl-3-{2-[4-(4-methoxy-phenyl)-[1,2,3]triazol-1-yl]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (133), 5-amino-3-[2-(1,3-dihydro-isoindol-2-yl)-ethyl]-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (134), 5-amino-8-furan-2-yl-1-methyl-3-(2-piperidin-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (135), 5-amino-8-furan-2-yl-1-methyl-3-(2-pyrrolidin-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (136), 5-amino-8-furan-2-yl-1-methyl-3-[2-(3-methyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-ethyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (137), 5-amino-8-furan-2-yl-3-{2-[4-(2-methoxy-ethoxy)-phenoxy]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (138), 5-amino-8-furan-2-yl-3-{2-[4-(2-methoxy-ethoxy)-phenylamino]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (139), 5-amino-8-furan-2-yl-1-methyl-3-[2-(pyridin-2-yloxy)-ethyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (140), 5-amino-1-ethyl-3-{2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethyl}-8-isothiazol-5-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (141), 5-amino-1-ethyl-8-isothiazol-5-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (142), 5-amino-1-ethyl-8-furan-2-yl-3-(2-piperidin-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (143), 5-amino-1-ethyl-8-furan-2-yl-3-[2-(3-methyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-ethyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (144), 5-amino-3-[2-(2,4-difluoro-phenoxy)-ethyl]-1-ethyl-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (145), 5-amino-3-[2-(2,4-difluoro-phenylamino)-ethyl]-1-ethyl-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (146), 5-amino-1-cyclopropylmethyl-3-[2-(2,4-difluoro-phenylamino)-ethyl]-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (147), 5-amino-1-cyclopropylmethyl-3-[2-(2,4-difluoro-phenoxy)-ethyl]-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (148), 5-amino-1-cyclopropylmethyl-3-{2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-ethyl}-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (149), 5-amino-3-{2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-ethyl}-8-furan-2-yl-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (150), 5-amino-8-furan-2-yl-3-{2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (151), 5-amino-3-[2-(4-cyclopropylmethyl-piperazin-1-yl)-ethyl]-8-isothiazol-5-yl-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (152), (5-amino-8-isothiazol-5-yl-3-{2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-2-oxo-2,3-dihydro-[1,2,4]triazolo[5,1-i]purin-1-yl)-acetonitrile (153), [5-amino-3-{2-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-ethyl}-8-(3-fluoro-phenyl)-2-oxo-2,3-dihydro-[1,2,4]triazolo[5,1-i]purin-1-yl]-acetonitrile (154), [5-amino-8-furan-2-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-2-oxo-2,3-dihydro-[1,2,4]triazolo[5,1-i]purin-1-yl]-acetonitrile (155), 5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-8-phenyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (156), 3-[5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-2-oxo-2,3-dihydro-1H-[1,2,4]triazolo[5,1-i]purin-8-yl]-benzonitrile (157), 3-[5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-2-oxo-2,3-dihydro-1H-[1,2,4]triazolo[5,1-i]purin-8-yl]-benzonitrile (158), 5-Amino-8-furan-2-yl-1-methyl-3-vinyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (159) 5-amino-3-[3-(4-fluoro-phenyl)-prop-2-ynyl]-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (160), 5-amino-8-furan-2-yl-1-methyl-3-[4-(4-methyl-piperazin-1-yl)-but-2-ynyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (161), 5-amino-8-furan-2-yl-1-isopropyl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (162), 5-amino-2-benzyl-7-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-9-methyl-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (163), 5-amino-2-benzyl-9-methyl-7-(2-morpholin-4-yl-ethyl)-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (164), 5-amino-2-(3-chloro-benzyl)-7-[2-(4-isopropyl-piperazin-1-yl)-ethyl]-9-methyl-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (165), 5-amino-2-cyclopropylmethyl-9-methyl-7-(2-morpholin-4-yl-ethyl)-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (166), 5-amino-2-cyclopropylmethyl-7-(2,4-difluoro-benzyl)-9-methyl-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (167), 4-amino-2-furan-2-yl-6-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-6H-8-oxa-1,3,3a,5,6-pentaaza-as-indacen-7-one (168), and 4-Amino-2-furan-2-yl-6-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-8,8-dimethyl-6,8-dihydro-1,3,3a,5,6-pentaaza-as-indacen-7-one (169) The present invention provides a pharmaceutical composition selected from the group consisting of:

[0118] In an embodiment of the present disclosure, A 2A / A 2B and a pharmaceutical composition comprising a compound of formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition.

[0119] [ka]

[0120] [In the formula, Y is selected from N or CR, and R is selected from H, hydroxy, alkoxy, alkyl, or aryl; R 1 is a group in which one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), with the proviso that the heteroatom is not adjacent to the N in the ring and p is selected from 0, 1, or 2, where alkyl, alkenyl, and alkynyl are unsubstituted or are selected from alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SOH, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, -S(O)NR a R a , -NR a S(O)2R a , or -S(O) p R a are independently substituted with R 2is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, haloalkyl, haloalkyloxy, alkoxy, -NR b R b , -S(O) p R b , cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy; wherein alkyl, alkenyl, alkynyl, alkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, and R b is unsubstituted or alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO3H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O)p R d and is substituted with 1, 2, or 3 substituents independently selected from R 3 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SOH, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from X is optionally substituted arylene or optionally substituted heteroarylene; A is a bond, 1 to 4 methylene groups are O, -S(O)p -, -N(R b )-, or —C(O)—, where alkylene, alkenylene, and alkynylene are unsubstituted or selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, —SOH, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl, or heteroaryl, wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R a are independently selected from hydrogen or alkyl; R b is independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R cis selected from hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl; R d is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; p is 0, 1 or 2].

[0121] In an embodiment of the present disclosure, A 2A / A 2B and a pharmaceutical composition comprising a compound of formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. [In the formula, Y is N, R 1 is selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein the alkyl, alkenyl, and alkynyl are unsubstituted or independently substituted with alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxyl, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, or carboxyalkyl; R 2 is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, haloalkyl, haloalkyloxy, alkoxy, -NR b R b , -S(O) p R b, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy; wherein alkyl, alkenyl, alkynyl, alkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, and R b is unsubstituted or alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxyl, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SOH, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O)NR c R c , -NR c S(O)2R c or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxyl, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R 3is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; wherein alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or substituted with alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxyl, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO3H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or may be alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano, or -S(O). p R d and is substituted with 1, 2, or 3 substituents independently selected from X is optionally substituted arylene or optionally substituted heteroarylene; A is a bond, 1 to 4 methylene groups are O, -S(O) p -, -N(R b)-, or —C(O)—; wherein alkylene, alkenylene, and alkynylene are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxyl, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SO3H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or may be alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxyl, alkoxy, halogen, CF3, amino, substituted amino, cyano, or -S(O). p R d and is substituted with 1, 2, or 3 substituents independently selected from B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl, or heteroaryl; wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxyl, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or may be alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R a are independently selected from the group consisting of hydrogen and alkyl; R b is independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R cis selected from hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl; R d is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; p is 0, 1 or 2].

[0122] In an embodiment of the present disclosure, A 2A / A 2B and a pharmaceutical composition comprising a compound of formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. wherein Y is CR; R is selected from the group consisting of H, hydroxy, alkoxy, alkyl, and aryl; R 1 is selected from the group consisting of alkyl, alkenyl, and alkynyl, wherein the alkyl, alkenyl, and alkynyl are unsubstituted or independently substituted with alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, or carboxyalkyl; R 2 is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, haloalkyl, haloalkyloxy, alkoxy, and -NR b R b is selected from the group consisting of where alkyl, alkenyl, alkynyl, alkoxy and R bis unsubstituted or independently substituted with alkylalkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO3H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, or cycloalkenyl; R 3 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; X is an optionally substituted heteroarylene; A is a bond, 1 to 4 methylene groups are O, -S(O) p , -N(R b )-, and —C(O)—, optionally replaced by a group independently selected from the group consisting of —C(O)—, —C(O)—, and —C(O)—; B is selected from the group consisting of heterocyclyl, cycloalkyl, aryl, and heteroaryl; wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, and -S(O). p R d and is substituted with one, two, or three substituents independently selected from the group consisting of: R b is independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R d is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl; p is 0, 1 or 2].

[0123] In an embodiment of the present disclosure, A 2A / A 2B and a pharmaceutical composition comprising a compound of formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. wherein Y is N or CR; and R is selected from the group consisting of H, hydroxy, alkoxy, alkyl, and aryl; R 1 is selected from the group consisting of alkyl, alkenyl, and alkynyl; R 2 is selected from the group consisting of heterocyclyl, heterocyclyloxy, heteroaryl, and heteroaryloxy; wherein heterocyclyl, heterocyclyloxy, heteroaryl, and heteroaryloxy are unsubstituted or independently substituted with alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO3H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, or cycloalkenyl; R 3 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; X is an optionally substituted phenyl; A is a bond, 1 to 4 methylene groups are O, -S(O) p -, -N(R b)-, and —C(O)—, optionally replaced by a group independently selected from the group consisting of —C(O)—, —C(O)—, and —C(O)—; B is selected from the group consisting of heterocyclyl, cycloalkyl, aryl, and heteroaryl; wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, and -S(O). p R d and is substituted with one, two, or three substituents independently selected from the group consisting of: R bis independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R d is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl; p is 0, 1 or 2].

[0124] In an embodiment of the present disclosure, A 2A / A 2B and a pharmaceutical composition comprising a compound of formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. [In the formula, Y is N, R 1 is a group in which one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a )-, or alkyl substituted by a group such as -C(O), provided that the heteroatom is not adjacent to the N in the ring and p is 0, 1, or 2; wherein alkyl is unsubstituted or is alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO3H, aminocarbonylamino, hydroxyamino, alkoxyamino, -S(O)2NR a R a , -NR a S(O)2R a , or -S(O) p R a are independently substituted with ; R 2is selected from the group consisting of heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy; wherein heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy are unsubstituted or selected from alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SOH, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O)NR c R c , -NR c S(O)2R c or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, and -S(O). p R d and is substituted with one, two, or three substituents independently selected from the group consisting of: R 3 is selected from the group consisting of hydrogen, alkyl, and arylalkyl; X is an optionally substituted heteroarylene; A is a group in which 1 to 4 methylene groups are O, -S(O) p -, -N(R b)-, and —C(O)—, optionally replaced by a group independently selected from —C(O)—, —C(O)—, and —C(O)—; wherein alkylene, alkenylene, and alkynylene are unsubstituted or substituted with alkyl, alkoxy, cycloalkyl, halogen, hydroxy, hydroxyalkyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, —SO3H, hydroxyamino, alkoxyamino, S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d are independently substituted with B is selected from the group consisting of heterocyclyl, cycloalkyl, aryl, and heteroaryl; wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, and -S(O). p R d and is substituted with one, two, or three substituents independently selected from the group consisting of: R a are independently selected from the group consisting of hydrogen and alkyl; R b is independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, and heterocyclyl; R d is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl; p is 0, 1 or 2].

[0125] In an embodiment of the disclosure, there is provided a pharmaceutical composition comprising a compound of Formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0126] In an embodiment of the present disclosure, A 2A / A 2BA method of using a pharmaceutical composition comprising a compound of Formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in the treatment of a disease or condition in a mammal amenable to treatment with a receptor antagonist is provided, the method comprising administering to a mammal in need thereof a therapeutically effective amount of the pharmaceutical composition disclosed herein.

[0127] In an embodiment of the present disclosure, A 2A / A 2B A method for treating a disorder or condition ameliorated by antagonizing a receptor is provided, comprising administering to a patient in need of such treatment an effective amount of a pharmaceutical composition comprising a compound of Formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof.

[0128] In an embodiment of the disclosure, there is provided a use of a pharmaceutical composition comprising a compound of Formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for preparing a medicament for the treatment of a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0129] In embodiments of the disclosure, there is provided a pharmaceutical composition comprising a compound of Formula II, pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in combination with at least one PD-L1 antibody for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0130] In embodiments of the disclosure, there is provided the use of a pharmaceutical composition comprising a compound of Formula II, pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in combination with at least one PD-L1 antibody for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0131] In an embodiment of the disclosure, there is provided a pharmaceutical composition comprising a compound of formula II, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, wherein the compound of formula II is 8-(4-benzyloxy-phenyl)-1-propyl-1,7-dihydro-purin-6-one (170), 1-Propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (171), 8-(1-benzyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (170), 2-chloro-8-[1-(2,3-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (172), 2-chloro-8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (173), 2-chloro-1-propyl-8-[1-(4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (174), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (175), 8-[1-(2,3-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (176), 1-Propyl-8-[1-(4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (177), 1-Propyl-8-(1H-pyrazol-4-yl)-1,7-dihydro-purin-6-one (178), 2-chloro-8-[1-(3-fluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (179), 8-[1-(2,4-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (180), 2-chloro-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (181), 8-{4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy]-phenyl}-1-propyl-1,7-dihydro-purin-6-one (182), 8-{4-[5-oxo-1-(4-trifluoromethoxy-phenyl)-pyrrolidin-3-ylmethoxy]-phenyl}-1-propyl-1,7-dihydro-purin-6-one (183), 1-Propyl-8-{4-[3-(3-trifluoromethyl-phenyl)-prop-2-ynyloxy]-phenyl}-1,7-dihydro-purin-6-one (184), 8-{4-[5-oxo-1-(3-trifluoromethyl-phenyl)-pyrrolidin-3-ylmethoxy]-phenyl}-1-propyl-1,7-dihydro-purin-6-one (185), 2-chloro-8-[1-(2,4-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (186), 8-[1-(3-fluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (187), 2-morpholin-4-yl-1-propyl-8-[1-(4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (188), N-(4-cyano-phenyl)-2-[4-(6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-phenoxy]-acetamide (189), [4-(6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-phenoxy]-acetic acid (190), 8-(1-benzyl-1H-pyrazol-4-yl)-2-chloro-1-propyl-1,7-dihydro-purin-6-one (191), 8-(4-{2-oxo-2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethoxy}-phenyl)-1-propyl-1,7-dihydro-purin-6-one (192), 8-(1-benzyl-1H-pyrazol-4-yl)-1-propyl-2-(4-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (193), 8-(1-benzyl-1H-pyrazol-4-yl)-1-propyl-2-(3-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (194), 8-(1-benzyl-1H-pyrazol-4-yl)-2-[2-(4-methoxy-phenyl)-ethylamino]-1-propyl-1,7-dihydro-purin-6-one (195), 8-(1-benzyl-1H-pyrazol-4-yl)-2-phenethylamino-1-propyl-1,7-dihydro-purin-6-one (196), 8-(1-benzyl-1H-pyrazol-4-yl)-2-(4-methyl-piperazin-1-yl)-1-propyl-1,7-dihydro-purin-6-one (197), 8-(1-benzyl-1H-pyrazol-4-yl)-2-piperidin-1-yl-1-propyl-1,7-dihydro-purin-6-one (198), 8-{1-[1-(2,4-difluoro-phenyl)-5-oxo-pyrrolidin-3-ylmethyl]-1H-pyrazol-4-yl}-1-propyl-1,7-dihydro-purin-6-one (199), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-2-(2-hydroxy-ethylamino)-1-propyl-1,7-dihydro-purin-6-one (200), 2-amino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (201), 8-(1-benzyl-1H-pyrazol-4-yl)-2-methylamino-1-propyl-1,7-dihydro-purin-6-one (202), [8-(1-benzyl-1H-pyrazol-4-yl)-6-oxo-1-propyl-6,7-dihydro-1H-purin-2-ylamino]-acetic acid ethyl ester (203), 8-(1-benzyl-1H-pyrazol-4-yl)-2-methoxy-1-propyl-1,7-dihydro-purin-6-one (204), 1,2-Dipropyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (205), 1-Propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-2-(4-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (206), 1-Propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (207), 2-(3-fluoro-phenyl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (208), 2-Dimethylamino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (209), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6-oxo-1-propyl-6,7-dihydro-1H-purine-2-carbonitrile (210), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6-oxo-1-propyl-6,7-dihydro-1H-purine-2-carboxylic acid (211), 8-(4-benzyloxy-phenyl)-1-propyl-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (212), 8-{4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy]-phenyl}-1-propyl-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (213), 8-(4-Methoxy-phenyl)-1-propyl-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (214), 2-ethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (215), 2-benzyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (216), {6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-ylamino}-acetic acid (217), (S)-1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (218), 1-Propyl-2-pyrrolidin-1-yl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (219), 2-Methylamino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (220), 2-Cyclobutylamino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (221), 2-chloro-8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-7-methyl-1-propyl-1,7-dihydro-purin-6-one (222), 2-Methoxy-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (223), 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carbonitrile (224), 2-Cyclopentyloxy-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (225), 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carboxylic acid amide (226), {6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yloxy}-acetic acid ethyl ester (227), 2-morpholin-4-yl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (228), {6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yloxy}-acetic acid (229), 8-{1-[3-(4-fluoro-phenyl)-prop-2-ynyl]-1H-pyrazol-4-yl}-1-propyl-2-pyrrolidin-1-yl-1,7-dihydro-purin-6-one (230), (S)-1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid amide (231), 1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-piperidine-3-carboxylic acid (232), 1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-piperidine-4-carboxylic acid (233), (2R,4R)-4-hydroxy-1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (234), 2-(2,3-dihydroxy-propylamino)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (235), 2-(2-Methoxy-ethylamino)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (236), 2-(4-hydroxy-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (237), 2-(3-hydroxy-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (238), 2-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-ylamino}-ethanesulfonic acid (239), 2-(3-hydroxymethyl-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (240), (Methyl-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-amino)-acetic acid (241), 2-(2-hydroxy-ethylamino)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (242), 2-(4-hydroxymethyl-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (243), 2-(4-hydroxymethyl-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (244), (S)-3-methyl-2-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-ylamino}-butyric acid (245), 2-((S)-2-Methoxymethyl-pyrrolidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (246), 2-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (247), 2-((R)-3-hydroxy-pyrrolidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (248), 1-Propyl-2-(tetrahydro-pyran-4-ylamino)-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (249), 2-Fluoro-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (250), 1-Propyl-2-(2,2,2-trifluoro-ethoxy)-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (251), 2-(2-Methoxy-ethoxy)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (252), 7-methyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (253), 2-chloro-1-propyl-8-[6-(3-trifluoromethyl-benzylamino)-pyridin-3-yl]-1,7-dihydro-purin-6-one (254), 2-chloro-8-[6-(3-fluoro-benzylamino)-pyridin-3-yl]-1-propyl-1,7-dihydro-purin-6-one (255), 1-Propyl-8-[6-(3-trifluoromethyl-benzylamino)-pyridin-3-yl]-1,7-dihydro-purin-6-one (256), 1-Propyl-8-(1-pyridin-3-ylmethyl-1H-pyrazol-4-yl)-1,7-dihydro-purin-6-one (257), 1-Propyl-8-[1-(6-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (258), 2-Cyclopropyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (259), 2-Difluoromethoxy-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (260), 1-Propyl-2-trifluoromethyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (261), 2-chloro-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (262), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (263), 2-Isobutylamino-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (264), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-pyrrolidin-1-yl-1,7-dihydro-purin-6-one (265), 2-[2-(4-methoxy-phenyl)-ethylamino]-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (266), 2-(4-methyl-piperazin-1-yl)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (267), 2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (268), 1-[8-(1-methyl-1H-pyrazol-4-yl)-6-oxo-1-propyl-6,7-dihydro-1H-purin-2-yl]-pyrrolidine-2-carboxylic acid methyl ester (269), 2-benzyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (270), 2-(3-fluoro-phenyl)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (271), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-(4-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (272), 8-(1-methyl-1H-pyrazol-4-yl)-2-phenethylamino-1-propyl-1,7-dihydro-purin-6-one (273), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-(4-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (274), 2-Cyclopropylamino-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (275), 2-(3-fluoro-phenoxy)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (276), 2-(4-Methoxy-phenylamino)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (277), 7-benzyl-2-chloro-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (278), 9-benzyl-2-chloro-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,9-dihydro-purin-6-one (279), 2-amino-7-benzyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (280), 2-chloro-8-furan-2-yl-1-propyl-1,7-dihydro-purin-6-one (281), 2-amino-8-[1-(4-fluoro-benzyl)-1H-imidazo[1,2-b]pyrazol-7-yl]-1-propyl-1,7-dihydro-purin-6-one (282), 2-chloro-8-[1-(4-fluoro-benzyl)-1H-imidazo[1,2-b]pyrazol-7-yl]-1-propyl-1,7-dihydro-purin-6-one (283), 2-amino-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (284), 2-amino-7-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (285), 2-amino-9-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,9-dihydro-purin-6-one (286), 7-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (287), 9-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,9-dihydro-purin-6-one (288), 2-amino-8-furan-2-yl-1-propyl-1,7-dihydro-purin-6-one (289), 2-chloro-8-furan-2-yl-7-methyl-1-propyl-1,7-dihydro-purin-6-one (290), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-(3-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (291), 2-furan-2-yl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (292), 8-(1-benzyl-1H-pyrazol-4-yl)-2-furan-2-yl-1-propyl-1,7-dihydro-purin-6-one (293), 2-chloro-8-(6-chloro-pyridin-3-yl)-1-propyl-1,7-dihydro-purin-6-one (294), 2-Difluoromethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (295), 2-Fluoromethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (296), 2-Fluoromethyl-8-{1-[3-(3-methoxy-phenyl)-prop-2-ynyl]-1H-pyrazol-4-yl}-1-propyl-1,7-dihydro-purin-6-one (297), 2-Difluoromethyl-8-{1-[2-oxo-2-(4-m-tolyl-piperazin-1-yl)-ethyl]-1H-pyrazol-4-yl}-1-propyl-1,7-dihydro-purin-6-one (298), 3-Fluoro-N-methyl-N-[5-(6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-benzamide (299), N-[5-(2-difluoromethyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-N-methyl-benzamide (300), N-[5-(2-difluoromethyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (301), 2-Fluoromethyl-1-propyl-8-[1-(5-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (302), 2-Fluoromethyl-1-propyl-8-[1-(2-trifluoromethyl-pyridin-4-ylmethyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (303), 2-Fluoromethyl-8-[3-(3-methoxy-phenoxy)-isoxazol-5-yl]-1-propyl-1,7-dihydro-purin-6-one (304), 2-Difluoromethyl-8-{3-[3-(3-fluoro-phenyl)-prop-2-ynyloxy]-isoxazol-5-yl}-1-propyl-1,7-dihydro-purin-6-one (305), 2-Fluoromethyl-1-(2-hydroxy-ethyl)-8-[3-(3-methoxy-phenoxy)-isoxazol-5-yl]-1,7-dihydro-purin-6-one (306), 2-Difluoromethyl-1-ethyl-8-{3-[3-(3-fluoro-phenyl)-prop-2-ynyloxy]-isoxazol-5-yl}-1,7-dihydro-purin-6-one (307), 2-Difluoromethyl-1-ethyl-8-(1-{2-[4-(3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-1H-pyrazol-4-yl)-1,7-dihydro-purin-6-one (308), 1-ethyl-8-(1-{2-[4-(3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-1H-pyrazol-4-yl)-6-oxo-6,7-dihydro-1H-purine-2-carbonitrile (309), N-[5-(2-cyano-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (310), N-{5-[2-cyano-1-(2-hydroxy-ethyl)-6-oxo-6,7-dihydro-1H-purin-8-yl]-pyridin-2-yl}-3-methoxy-benzenesulfonamide (311), 2-Difluoromethyl-1-ethyl-8-{4-[3-(3-methoxy-phenyl)-prop-2-ynyloxy]-phenyl}-1,7-dihydro-purin-6-one (312), 2-Difluoromethyl-1-ethyl-8-{4-[1-(3-fluoro-phenyl)-5-oxo-pyrrolidin-3-ylmethoxy]-phenyl}-1,7-dihydro-purin-6-one (313), 2-Difluoromethyl-8-[5-(3-methoxy-phenoxy)-1-methyl-1H-pyrazol-3-yl]-1-propyl-1,7-dihydro-purin-6-one (314), 2-Difluoromethyl-8-{5-[1-(3-methoxy-phenyl)-piperidin-4-yloxy]-1-methyl-1H-pyrazol-3-yl}-1-propyl-1,7-dihydro-purin-6-one (315), 2-Fluoromethyl-8-{3-[1-(3-fluoro-phenyl)-piperidin-4-yloxy]-isoxazol-5-yl}-1-propyl-1,7-dihydro-purin-6-one (316), 1-ethyl-8-{6-[1-(3-fluoro-phenyl)-5-oxo-pyrrolidin-3-ylmethoxy]-pyridin-3-yl}-6-oxo-6,7-dihydro-1H-purine-2-carbonitrile (317), 1-ethyl-8-{6-[1-(3-methoxy-phenyl)-pyrrolidin-3-yloxy]-pyridin-3-yl}-6-oxo-6,7-dihydro-1H-purine-2-carbonitrile (318), 3-[4-(2-difluoromethyl-1-ethyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-pyrazol-1-ylmethyl]-benzoic acid (319), 2-Difluoromethyl-1-ethyl-8-[1-(3-hydroxymethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (320), 2-Difluoromethyl-3-ethyl-6-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (321), N-[5-(2-cyano-4-oxo-3-propyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-6-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (322), 2-fluoromethyl-6-{3-[1-(3-fluoro-phenyl)-piperidin-4-yloxy]-isoxazol-5-yl}-3-propyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (323), 2-Difluoromethyl-6-{5-[1-(3-methoxy-phenyl)-piperidin-4-yloxy]-1-methyl-1H-pyrazol-3-yl}-3-propyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (324), 3-ethyl-6-{6-[1-(3-methoxy-phenyl)-pyrrolidin-3-yloxy]-pyridin-3-yl}-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-2-carbonitrile (325), 2-Fluoromethyl-6-{3-[1-(3-fluoro-phenyl)-piperidin-4-yloxy]-isoxazol-5-yl}-7-hydroxy-3-propyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (326), 2-Difluoromethyl-3-ethyl-6-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-7-methyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (327), 2-Difluoromethyl-1-ethyl-8-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-7-methyl-1,7-dihydro-purin-6-one (328), N-[5-(2-cyano-7-methyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (329), 1-(2,2-difluoro-ethyl)-2-ethyl-8-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (330), 3-{3-[4-(2-difluoromethyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyrazol-1-yl]-prop-1-ynyl}-benzoic acid (331), 3-(3-{4-[1-(2,2-difluoro-ethyl)-2-ethyl-6-oxo-6,7-dihydro-1H-purin-8-yl]-pyrazol-1-yl}-prop-1-ynyl)-benzoic acid (332), 3-{3-[4-(6-oxo-1-propyl-2-trifluoromethyl-6,7-dihydro-1H-purin-8-yl)-pyrazol-1-yl]-prop-1-ynyl}-benzoic acid (333), and 6-Oxo-1-propyl-8-[6-(3-trifluoromethyl-benzyl)-pyridin-3-yl]-6,7-dihydro-1H-purine-2-carbonitrile (334) The present invention provides a pharmaceutical composition selected from the group consisting of:

[0132] In an embodiment of the present disclosure, A 2A / A 2B and a compound of formula III or IV, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition.

[0133] [ka]

[0134] [In the formula, R 1 is a group in which one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), provided that the heteroatom is not adjacent to the N in the ring and p is selected from 0, 1 or 2; wherein alkyl is unsubstituted or substituted with alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -aminocarbonylamino, hydroxyamino, alkoxyamino; R 2 is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, haloalkyl, haloalkyloxy, alkoxy, -NR b R b , -S(O) p R b , cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy; Here, alkyl, alkenyl, alkynyl, alkoxy, carboxyalkyl, cycloalkyl alkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, and R bis unsubstituted or alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO3H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d are independently substituted with ; Each substituent is unsubstituted or is alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R' and R" are independently selected from hydrogen or alkyl; R' and R" together can represent O or a saturated or partially unsaturated lower cycloalkyl ring system; R 3 is alkyl, aryl, -C(O)R 4 and -P(O)(OR 5 )2, R 4 is alkyl, alkoxy, aryl, heteroaryl, heterocyclyl, or -NR 6 R 7 is selected from R 5is selected from hydrogen, alkyl, aryl, arylalkyl, —CHOC(O)alkyl, or —CHOC(O)Oalkyl, or two R 5 the groups taken together form a 5- or 6-membered ring system which is saturated or partially unsaturated and optionally substituted with 1 to 4 substituents independently selected from halo, alkyl, aryl, or heteroaryl; R 6 and R 7 is independently selected from the group consisting of hydrogen, alkyl, heterocyclyl, and heterocyclylalkyl; or R 6 and R 7 together form a monocyclic ring system that is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N, or S, wherein the ring system is not substituted with a halo, alkyl, alkoxy, or -NR 8 R 9 and optionally substituted with 1 to 4 substituents independently selected from R 4 , R 5 , R 6 and R 7 is hydroxyl, halogen, alkyl, alkoxy, haloalkyl, -NR 8 R 9 , -C(O)OR 10 , -OC(O)R 10 or -NC(O)R 10 and optionally substituted with 1 to 4 substituents independently selected from R 8 and R 9 are independently selected from the group consisting of hydrogen and alkyl; R 10 is selected from hydrogen, hydroxy, halogen, amino, substituted amino, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, carboxy, carboxyalkyl, aminocarbonyl, aryl, or arylalkyl; X is optionally substituted arylene or optionally substituted heteroarylene; A is a bond or 1 to 4 methylene groups are O, -S(O)p -, -N(R b )-, or -C(O)-, where alkylene is unsubstituted or is selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SO3H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O)2NR c R c , -NR c S(O)2R c or -S(O) p R d are independently substituted with ; Each substituent may be unsubstituted or may be alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF3, amino, substituted amino, cyano, or -S(O). p R d and is substituted with 1, 2, or 3 substituents independently selected from B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl, or heteroaryl, wherein heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO3H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O)2NR b R b , -NR b S(O)2R b or -S(O) p R d each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from D is -O-, -S(O)p-, or -N(R a )-selected from R a is hydrogen or alkyl, R bis selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl; R d is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; p is 0, 1 or 2; t is 1 or 2].

[0135] In an embodiment of the present disclosure, A 2A / A 2B and a compound of formula III or IV, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition. [In the formula, R 1 is alkyl, R 2 is selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, hydroxyalkyl, haloalkyl, haloalkyloxy, and alkoxy; R' and R" are independently selected from hydrogen or alkyl; R 3 is alkyl, -C(O)R 4 and -P(O)(OR 5 )2, R 4 is selected from alkyl or alkoxy; R 5 is selected from the group consisting of hydrogen, alkyl, —CHOC(O)alkyl, or —CHOC(O)Oalkyl; R 4 and R 5 is hydroxyl, halogen, alkyl, alkoxy, haloalkyl, -NR8 R 9 , -C(O)OR 10 , -OC(O)R 10 or -NC(O)R 10 and optionally substituted with 1 to 4 substituents independently selected from R° and R * are independently selected from the group consisting of hydrogen and alkyl; R 10 is selected from the group consisting of hydrogen, hydroxy, halogen, amino, substituted amino, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, carboxy, carboxyalkyl, aminocarbonyl, aryl, and arylalkyl; X is an optionally substituted heteroarylene; A is selected from a bond or (C1-C6) alkylene; B is selected from aryl or heteroaryl, wherein aryl and heteroaryl are unsubstituted or independently substituted with alkyl, alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, haloalkyl, perhaloalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy -SOH, aminocarbonylamino, hydroxyamino, alkoxyamino, or nitro; D is -O-, -S(O)p-, or -N(R a )-selected from R a is hydrogen or alkyl, p is 0, 1 or 2; t is 1 or 2].

[0136] In an embodiment of the disclosure, there is provided a pharmaceutical composition comprising a compound of Formula III or IV, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0137] In an embodiment of the present disclosure, A 2A / A 2B A method of using a pharmaceutical composition comprising a compound of Formula III or IV, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in the treatment of a disease or condition in a mammal amenable to treatment with a receptor antagonist, is provided, comprising the step of administering to a mammal in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula III or IV, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof.

[0138] In an embodiment of the present disclosure, A 2A A method for treating a disorder or condition ameliorated by antagonizing a receptor is provided, comprising administering to a patient in need of such treatment an effective amount of a pharmaceutical composition comprising a compound of Formula III or IV, pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof.

[0139] In an embodiment of the present disclosure, there is provided a use of a pharmaceutical composition comprising a compound of Formula III or IV, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, for preparing a medicament for the treatment of a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0140] In embodiments of the disclosure, there is provided a pharmaceutical composition comprising a compound of Formula III or IV, pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in combination with at least one PD-L1 antibody for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0141] In embodiments of the disclosure, there is provided the use of a pharmaceutical composition comprising a compound of Formula III or IV, pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, in combination with at least one PD-L1 antibody for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

[0142] In an embodiment of the disclosure, there is provided a pharmaceutical composition comprising a compound of formula III or IV, its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof, wherein the compound of formula III or formula IV is phosphoric acid mono-{2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (335), mono-{2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl}phosphate disodium salt (336), phosphoric acid mono-{2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (337), phosphoric acid mono-{2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl} ester (338), 2,2-Dimethyl-propionic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (339), 2,2-Dimethyl-propionic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (340), 2,2-Dimethyl-propionic acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (341), 7-Methoxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (342), 9-Methoxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,9-dihydro-purin-6-one (343), 2-chloro-7-methoxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (344), mono-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl}phosphate (345), (2-Dimethylamino-ethyl)-methyl-carbamic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (346), (1-Ethyl-pyrrolidin-2-ylmethyl)-carbamic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (347), Nicotinic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (348), Acetic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (349), Butyric acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (350), Butyric acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (351), Nicotinic acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (352), (2-Dimethylamino-ethyl)-methyl-carbamic acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (353), (2-Dimethylamino-ethyl)-methyl-carbamic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (354), Butyric acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (355), 2,2-Dimethyl-propionic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (356), Nicotinic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (357), 4-Methyl-piperazine-1-carboxylic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (358), 1-{6-oxo-7-phosphonooxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (359), 1-{7-(2,2-dimethyl-propionyloxymethyl)-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (360), 2,2-Dimethyl-propionic acid 2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (361), mono-{2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl}phosphate (362), phosphoric acid mono-{2-chloro-6-oxo-1-propyl-8-[1-(6-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (363), phosphoric acid mono-{6-oxo-1-propyl-8-[1-(6-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (364), Benzoic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (365), 7-Methoxymethyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carbonitrile (366), Acetic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (367), (S)-Pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-{2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (368), Butyric acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (369), Butyric acid 2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (370), Butyric acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (371), Butyric acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (372), phosphoric acid mono-{2-fluoro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl} ester (373), mono-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl}phosphate (374), or Mono-{2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl}phosphate (375) The present invention provides a pharmaceutical composition selected from the group consisting of:

[0143] In an embodiment of the present disclosure, A 2A / A 2B Provided is a pharmaceutical composition comprising a compound selected from a compound of Formula I, a compound of Formula II, a compound of Formula III, or a compound of Formula IV, for the manufacture of a medicament for the treatment of a condition or disorder ameliorated by receptor inhibition, the pharmaceutical composition further comprising a therapeutically effective amount of at least one pharmaceutically acceptable excipient. [Example]

[0144] Synthesis of Compounds of Formula I The compound of formula I was synthesized according to the procedures described in WO 2012038980, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds can be obtained according to procedures reported in the literature. [Example]

[0145] Synthesis of Compounds of Formula II The compound of formula II was synthesized according to the procedures described in WO 2010103547, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds can be obtained according to procedures reported in the literature. [Example]

[0146] Synthesis of Compounds of Formula III and Formula IV Compounds of formula III or IV were synthesized according to the procedures described in WO2012035548, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds can be obtained according to procedures reported in the literature.

[0147] The compounds of the present disclosure can be prepared by a variety of methods, including standard synthetic chemistry. Any previously defined variables will continue to have the previously defined meaning unless otherwise indicated. Exemplary general synthetic methods are presented in the schemes and can be easily adapted to prepare other compounds of the present disclosure. [Example]

[0148] Biological assays Adenosine A in cancer xenograft models 2A (Compound 31) antagonist and A 2B (Compound 169) antagonist tumor suppressor activity General protocol: 6-8 week old BALB / c mice were acclimated. On day 1 of the study, mice were inoculated with 5 x 10 4 4T1 cells (breast cancer) or 5 × 10 5On the 8th or 9th day, the mice were separated into different groups and injected with 50 μL of medium containing CT26 cells (colon cancer). On the 8th or 9th day, the mice were injected with either vehicle (1% Tween-80 in water + 0.5% carboxymethylcellulose) or the test compound [(Compound 32)] in vehicle. Oral treatment was performed with 5-amino-3-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (32) and mono-{2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester phosphate (335). Treatment was twice daily for 22 days (colon cancer) or 28 days (breast cancer). At the end of the study, tumor volume was measured as (length × width) / 2. Data are presented as the percent reduction compared to tumor volume in vehicle-treated animals.

[0149] [Table 1]

[0150] Although the subject matter has been described in considerable detail with reference to certain preferred embodiments thereof, other embodiments are possible, and therefore, the spirit and scope of the appended claims should not be limited to the description of the preferred embodiments contained therein.

Claims

1. A 2A / A 2B Pharmaceutical compositions for the treatment of conditions or disorders ameliorated by the inhibition of a receptor, comprising a compound of formula I and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof. 【Chemistry 1】 [In the formula, --- represents a single or double bond, X is O, S or NR a is selected from Y 1 is selected from N or CH; Y 2 is NR 5 , O or CR 5 R 6 is selected from Y 3 are N, CH, CH 2 , C(=O), or C(=S); Y 4 is selected from N, C, or CH; R 1 and R 2 are independently selected from hydrogen or alkyl; R 3 is -AZBQ, where A is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a )-, or —C(O), wherein alkylene, alkenylene, and alkynylene are groups selected from alkylene, alkenylene, and alkynylene, optionally substituted by groups such as —(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyano, halogen, haloalkyl, perhaloalkyl, alkoxyalkoxy, alkyl, or cycloalkyl; Z is absent or selected from cycloalkyl or heterocyclyl, where cycloalkyl and heterocyclyl are unsubstituted or selected from alkyl, alkenyl, alkynyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , aminocarbonyl, alkoxycarbonylamino, halogen, haloalkyl, perhaloalkyl, azido, cyano, keto, thiocarbonyl, -SO 3 H, aminocarbonylamino, nitro, -S(O) 2 NR a R a , -NR b S(O) 2 R b or -S(O) p R c and is independently substituted with 1, 2, or 3 substituents independently selected from B is absent or one or more methylene groups are replaced by a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), wherein the alkylene, alkenylene, and alkynylene are optionally substituted with hydroxy, amino, aminoalkyl, cyano, halogen, haloalkyl, perhaloalkyl, carboxy, carboxyalkyl, alkoxy, hydroxyalkyl, alkoxyalkyl, alkoxyalkoxy, or alkyl; Q is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, where alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, halogen, haloalkyl, perhaloalkyl, azido, cyano, nitro, keto, thiocarbonyl, cyanoalkyl, cyanoalkylcarbonyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , -(CR d R e ) n SR 7 , -(CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , -(CR d R e ) n C(O)NR 8 R 9 , -(CR d R e ) n NR 8 C(O)OR 7 , -(CR d R e ) n NR 8 C(O)NR 8 R 9 , -NR b S(O) 2 R b , -S(O) p R c , -SO 3 H, -S(O) 2 NR a R a , cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl, each of which is unsubstituted or substituted with one, two, or three substituents independently selected from alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, perhaloalkyl, haloalkoxy, perhaloalkoxy, amino, substituted amino, cyano, or -S(O) p R c and is substituted with 1, 2, or 3 substituents independently selected from R 4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl, where alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , aminocarbonyl, alkoxycarbonylamino, aminocarbonylamino, azido, cyano, halogen, haloalkyl, perhaloalkyl, keto, nitro, -S(O) 2 NR b R b , -NR b S(O) 2 R b or -S(O) p R c , thiocarbonyl, -SO 3 independently substituted with up to four substituents independently selected from H, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; R 5 and R 6 are independently hydrogen, hydroxy, -(CR d R e ) n OR 7 , (CR d R e ) n COOR 7 , -(CR d R e ) n NR 8 R 9 , cyanoalkyl, haloalkyl, alkoxyalkoxyalkyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, and heteroarylalkyl; R 7 is hydrogen, alkyl, halogen, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n COOR 7 , -(CR e R e ) n C(O)R 7 , carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl; R 8 and R 9 are independently hydrogen, alkyl, haloalkyl, -(CR d R e ) n OR 7 , -(CR d R e ) n C(O)R 7 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, and heterocyclylalkyl; or R 8 and R 9 together form a monocyclic or bicyclic ring system which is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N or S, said ring system being free of halo, alkyl, alkenyl, alkynyl, nitro, cyano, -(CR d R e ) n OR 7 , -(CR d R e ) n SR 7 , -(CR d R e ) n NR 8 R 9 , oxo, alkylsulfonyl, -(CR d R e ) n COOR 7 , -(CR d R e ) n C(O)NR 8 R 9 , cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl; R a is selected from hydrogen or alkyl; R b are each independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; R d and R e are independently hydrogen, -OR 7 , selected from the group consisting of halogen, haloalkyl, perhaloalkyl, and alkyl; n is 0, 1, 2, 3 or 4; p is 0, 1 or 2].

2. 10. The pharmaceutical composition of claim 1 for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

3. 10. The pharmaceutical composition of claim 1, in combination with at least one PD-L1 antibody, for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

4. The compound of formula I is 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (1), 5-amino-8-(2-furyl)-3-(2-hydroxyethyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (2), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (3), 5-amino-8-(2-furyl)-3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (4), 5-amino-8-(2-furyl)-1-methyl-3-(2-morpholinoethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (5), 5-amino-3-[2-[4-(2,4-difluorophenyl)-1-piperidyl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (6), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-(5-methyl-2-pyridyl)piperazin-1-yl] ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (7), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-(p-tolyl)piperazin-1-yl] ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (8), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-(3-methyl-2-oxo-butyl)piperazin-1-yl] ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (9), 5-amino-3-[2-[4-(2-fluoro-4-methoxy-phenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (10), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxy-1,1-dimethyl-ethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (11), 5-amino-8-(2-furyl)-3-[2-[4-(6-methoxy-3-pyridyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (12), 5-amino-3-[2-[4-[3-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (13), 5-amino-8-(2-furyl)-3-[2-[4-[4-(1-hydroxy-1-methyl-ethyl)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (14), 5-amino-3-[2-[4-(4-fluorophenyl)-4-hydroxy-1-piperidyl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (15), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxy-2-methyl-propoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (16), 5-amino-3-[2-[4-[4-(cyclopropoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (17), 5-amino-3-[2-[4-(4-fluorophenyl)-3,6-dihydro-2H-pyridin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (18), 5-amino-8-(2-furyl)-3-[2-[4-hydroxy-4-(4-methoxyphenyl)-1-piperidyl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (19), 5-amino-3-[2-[4-[3,5-difluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (20), 5-amino-3-[2-[4-[2,5-difluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (21), 5-amino-3-[2-[4-(2,2-difluoro-1,3-benzodioxol-5-yl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (22), 5-Amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]-3,3-dimethyl-piperazin-1-yl ]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (23), 5-amino-3-[2-(4-butylpiperazin-1-yl)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (24), 5-amino-8-(2-furyl)-3-[2-(4-hydroxy-4-methyl-1-piperidyl)ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (25), 5-amino-3-[2-[4-[4-[2-(cyclopropoxy)ethoxy]phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (26), 5-amino-8-(2-furyl)-3-[2-[4-[(4-methoxyphenyl)methyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (27), 5-amino-8-(2-furyl)-3-[2-[4-[[4-(2-methoxyethoxy)phenyl]methyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (28), 5-amino-8-(2-furyl)-3-[(4-methoxyphenyl)methyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (29), 5-amino-8-(2-furyl)-3-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (30), 5-amino-8-(2-furyl)-3-[2-[4-[3-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (31), 5-amino-3-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (32), 4-[4-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3yl ]ethyl]piperazin-1-yl]benzonitrile (33), 4-[4-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl ]ethyl]piperazin-1-yl]-2-fluoro-benzonitrile (34), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl] ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (35), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-[4-(trifluoromethyl)thiazol-2-yl]piperazin-1-yl] ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (36), 5-amino-3-[2-[4-(cyclopropylmethyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (37), 5-amino-3-[2-(4-ethylpiperazin-1-yl)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (38), 4-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N,N-dimethyl-piperazine-1-sulfonamide (39), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-(4-tetrahydrofuran-3-yloxyphenyl)piperazin-1-yl] ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (40), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-(4-tetrahydropyran-4-yloxyphenyl)piperazin-1-yl] ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (41), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-[4-(tetrahydrofuran-2-ylmethoxy)phenyl]piperazin-1-yl ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (42), 5-amino-8-(2-furyl)-1-methyl-3-[2-(3-methyl-7,8-dihydro-5H-1,6-naphthyridin-6-yl)ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (43), 5-amino-3-[2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (44), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]propyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (45), 5-amino-3-[2-[3-(4-fluorophenyl)-2,5-dihydropyrrol-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (46), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-(5-methyl-2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (47), 5-amino-8-(5-cyclopropyl-2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (48), 5-amino-3-[2-(2,4-difluoroanilino)ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (49), 5-amino-3-[3-[4-(4-fluorophenyl)piperazin-1-yl]propyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (50), 5-amino-8-(2-furyl)-3-[3-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]propyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (51), 5-amino-8-(2-furyl)-3-[2-[4-(4-methoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl ]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (52), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxy-1,1-dimethyl-ethyl)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (53), 5-amino-8-(2-furyl)-1-methyl-3-(2-piperazin-1-ylethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (54), 5-Amino-8-(2-furyl)-3-[2-[4-(1H-indole-2-carbonyl)piperazin-1-yl] ]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (55), 5-amino-8-(2-furyl)-3-[2-(4-isopropoxyphenyl)ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (56), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-[(2S)-pyrrolidine-2-carbonyl]piperazin-1-yl ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (57), 5-amino-8-(2-furyl)-3-[2-(4-methoxyphenyl)ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (58), 5-amino-3-[2-[4-[4-(difluoromethoxy)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (59), 5-Amino-8-(2-furyl)-1-methyl-3-[2-[4-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]piperazin-1-yl ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (60), 5-amino-3-[2-[4-[2-fluoro-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (61), 5-amino-3-[2-[4-(6-fluoro-2-methyl-1,3-benzoxazol-5-yl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (62), 5-amino-3-[2-[4-(cyclopropanecarbonyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (63), 5-amino-3-[2-[4-(2-cyclopropylacetyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (64), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-hydroxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (65), 5-amino-8-(2-furyl)-3-[2-[4-(4-hydroxyphenyl)piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (66), 5-amino-1-(cyclopropylmethyl)-3-[2-[4-(4-ethoxyphenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (67), 5-amino-1-(cyclopropylmethyl)-3-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (68), 5-amino-1-(cyclopropylmethyl)-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (69), 5-Amino-1-(cyclopropylmethyl)-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (70), 5-amino-1-(cyclopropylmethyl)-3-[2-(4-fluorophenoxy)ethyl]-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (71), 5-amino-8-(2-furyl)-1-methyl-3-[2-[2-oxo-5-(trifluoromethyl)-1-pyridyl ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (72), 5-amino-3-[2-[4-(2,4-difluorophenyl)pyrazol-1-yl]ethyl]-1-ethyl-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (73), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl ]ethyl]pyrazole-4-carboxylic acid (74), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl ]ethyl]pyrazole-4-carboxylic acid (75), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-pyrazole-4-carboxamide (76), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N,N-diethyl-pyrazole-4-carboxamide (77), 1-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-5-methyl-pyrazole-3-carboxamide (78), 2-[2-[5-amino-1-(cyclopropylmethyl)-8-(2-furyl)-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-5-methyl-pyrazole-3-carboxamide (79), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-methyl-pyrazole-3-carboxamide (80), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N,N-diethyl-pyrazole-4-carboxamide (81), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl ]ethyl]pyrazole-4-carboxamide (82), 5-amino-8-(2-furyl)-3-[2-[4-[(3R)-3-hydroxypyrrolidine-1-carbonyl]pyrazol-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (83), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-methyl-pyrazole-4-carboxamide (84), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-pyrazole-3-carboxamide (85), 1-[2-[5-amino-8-(2-furyl)-1-methyl-2-oxo-[1,2,4]triazolo[5,1-f]purin-3-yl]ethyl]-N-cyclopropyl-pyrazole-4-carboxamide (86), 5-amino-8-(2-furyl)-3-[2-[4-(3-hydroxyazetidine-1-carbonyl)pyrazol-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (87), 5-Amino-1-ethyl-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (88), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl] ]ethyl]-1-ethyl-8-(2-furyl)-[1,2,4]triazolo[5,1-f]purin-2-one (89), 5-amino-1-ethyl-3-{2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-ethyl}-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-f]purin-2-one (90), 5-amino-1-ethyl-8-(2-furyl)-3-[2-(3-methyl-7,8-dihydro-5H-1,6-naphthyridin-6-yl)ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (91), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (92), 5-amino-3-{2-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-ethyl}-8-furan-2-yl-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-f]purin-2-one (93), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-(2-methoxyethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (94), 5-amino-3-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-(2-methoxyethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (95), 5-amino-3-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl]-8-(2-furyl)-1-(2-hydroxyethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (96), 5-Amino-1-cyclopropyl-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-[1,2,4]triazolo[5,1-f]purin-2-one (97), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-(2,2,2-trifluoroethyl)-[1,2,4]triazolo[5,1-f]purin-2-one (98), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (99), 5-amino-3-[2-[4-[3-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (100), 5-amino-3-[2-[4-(2-cyclopropylacetyl)piperazin-1-yl] ]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (101), 5-amino-3-[2-[4-(4-methoxyphenyl)piperazin-1-yl ]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (102), 5-amino-1-methyl-3-[2-[4-(p-tolyl)piperazin-1-yl]ethyl]-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (103), 5-amino-1-methyl-3-[2-(3-methyl-7,8-dihydro-5H-1,6-naphthyridin-6-yl)ethyl]-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (104), 4-[4-[2-(5-amino-1-methyl-2-oxo-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-3-yl)ethyl]piperazin-1-yl]benzonitrile (105), 5-amino-1-methyl-3-[2-[4-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]piperazin-1-yl]ethyl]-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (106), 5-amino-3-[2-[4-[4-(1-hydroxy-1-methyl-ethyl)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-thiazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (107), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-2-one (108), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl] ]ethyl]-1-methyl-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-2-one (109), 4-[4-[2-[5-amino-1-methyl-2-oxo-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-3-yl ]ethyl]piperazin-1-yl]benzonitrile (110), 5-amino-3-[2-[4-[4-(1-hydroxy-1-methyl-ethyl)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-(2-pyridyl)-[1,2,4]triazolo[5,1-f]purin-2-one (111), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-pyrazin-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (112), 5-amino-3-[2-[4-(2,4-difluorophenyl)piperazin-1-yl] ]ethyl]-1-methyl-8-pyrazin-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (113), 5-amino-3-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-pyrazin-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (114), 5-amino-8-(2-furyl)-3-[[1-(4-methoxyphenyl)pyrrolidin-3-yl]methyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (115), 5-amino-8-(2-furyl)-3-[[1-[4-(2-methoxyethoxy)phenyl]pyrrolidin-3-yl]methyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one(hyl)}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (116), 5-amino-8-(2-furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purine-2-thione (117), 8-(2-Furyl)-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-5-(methylamino)-[1,2,4]triazolo[5,1-f]purin-2-one (118), 5-amino-3-{2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethyl}-8-isothiazol-5-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (119), 5-amino-8-isothiazol-5-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (120), 5-amino-3-[2-[4-[2-fluoro-4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-8-isothiazol-5-yl-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (121), 5-amino-8-isoxazol-5-yl-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-1-methyl-[1,2,4]triazolo[5,1-f]purin-2-one (122), 5-amino-3-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl ]ethyl]-1-methyl-8-oxazol-2-yl-[1,2,4]triazolo[5,1-f]purin-2-one (123), 5-amino-3-{2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-1-methyl-8-prop-1-ynyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (124), 5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-8-prop-1-ynyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (125), 5-amino-3-{2-[4-(4-fluoro-benzoyl)-piperazin-1-yl]-ethyl}-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (126), 5-amino-3-(2-dimethylamino-ethyl)-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (127), 5-amino-8-furan-2-yl-3-[3-(4-methoxy-phenyl)-propyl]-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (128), 5-amino-8-furan-2-yl-1-methyl-3-(2-pyrazol-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (129), 5-amino-8-furan-2-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-pyrazol-1-yl}-ethyl)-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (130), 5-amino-8-furan-2-yl-3-{2-[3-(4-methoxy-phenyl)-pyrrol-1-yl]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (131), 5-amino-8-furan-2-yl-3-{2-[4-(4-methoxy-phenyl)-imidazol-1-yl]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (132), 5-amino-8-furan-2-yl-3-{2-[4-(4-methoxy-phenyl)-[1,2,3]triazol-1-yl]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (133), 5-amino-3-[2-(1,3-dihydro-isoindol-2-yl)-ethyl]-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (134), 5-amino-8-furan-2-yl-1-methyl-3-(2-piperidin-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (135), 5-amino-8-furan-2-yl-1-methyl-3-(2-pyrrolidin-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (136), 5-amino-8-furan-2-yl-1-methyl-3-[2-(3-methyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-ethyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (137), 5-amino-8-furan-2-yl-3-{2-[4-(2-methoxy-ethoxy)-phenoxy]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (138), 5-amino-8-furan-2-yl-3-{2-[4-(2-methoxy-ethoxy)-phenylamino]-ethyl}-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (139), 5-amino-8-furan-2-yl-1-methyl-3-[2-(pyridin-2-yloxy)-ethyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (140), 5-amino-1-ethyl-3-{2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethyl}-8-isothiazol-5-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (141), 5-amino-1-ethyl-8-isothiazol-5-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (142), 5-amino-1-ethyl-8-furan-2-yl-3-(2-piperidin-1-yl-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (143), 5-amino-1-ethyl-8-furan-2-yl-3-[2-(3-methyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-ethyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (144), 5-amino-3-[2-(2,4-difluoro-phenoxy)-ethyl]-1-ethyl-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (145), 5-amino-3-[2-(2,4-difluoro-phenylamino)-ethyl]-1-ethyl-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (146), 5-amino-1-cyclopropylmethyl-3-[2-(2,4-difluoro-phenylamino)-ethyl]-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (147), 5-amino-1-cyclopropylmethyl-3-[2-(2,4-difluoro-phenoxy)-ethyl]-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (148), 5-amino-1-cyclopropylmethyl-3-{2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-ethyl}-8-furan-2-yl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (149), 5-amino-3-{2-[4-(4-fluoro-phenyl)-piperidin-1-yl]-ethyl}-8-furan-2-yl-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (150), 5-amino-8-furan-2-yl-3-{2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (151), 5-amino-3-[2-(4-cyclopropylmethyl-piperazin-1-yl)-ethyl]-8-isothiazol-5-yl-1-(2,2,2-trifluoro-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (152), (5-amino-8-isothiazol-5-yl-3-{2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-ethyl}-2-oxo-2,3-dihydro-[1,2,4]triazolo[5,1-i]purin-1-yl)-acetonitrile (153), [5-amino-3-{2-[4-(2,4-difluoro-phenyl)-piperazin-1-yl]-ethyl}-8-(3-fluoro-phenyl)-2-oxo-2,3-dihydro-[1,2,4]triazolo[5,1-i]purin-1-yl]-acetonitrile (154), [5-amino-8-furan-2-yl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-2-oxo-2,3-dihydro-[1,2,4]triazolo[5,1-i]purin-1-yl]-acetonitrile (155), 5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-8-phenyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (156), 3-[5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-2-oxo-2,3-dihydro-1H-[1,2,4]triazolo[5,1-i]purin-8-yl]-benzonitrile (157), 3-[5-amino-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1-methyl-2-oxo-2,3-dihydro-1H-[1,2,4]triazolo[5,1-i]purin-8-yl]-benzonitrile (158), 5-Amino-8-furan-2-yl-1-methyl-3-vinyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (159) 5-amino-3-[3-(4-fluoro-phenyl)-prop-2-ynyl]-8-furan-2-yl-1-methyl-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (160), 5-amino-8-furan-2-yl-1-methyl-3-[4-(4-methyl-piperazin-1-yl)-but-2-ynyl]-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (161), 5-amino-8-furan-2-yl-1-isopropyl-3-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-1,3-dihydro-[1,2,4]triazolo[5,1-i]purin-2-one (162), 5-amino-2-benzyl-7-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-9-methyl-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (163), 5-amino-2-benzyl-9-methyl-7-(2-morpholin-4-yl-ethyl)-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (164), 5-amino-2-(3-chloro-benzyl)-7-[2-(4-isopropyl-piperazin-1-yl)-ethyl]-9-methyl-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (165), 5-amino-2-cyclopropylmethyl-9-methyl-7-(2-morpholin-4-yl-ethyl)-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (166), 5-amino-2-cyclopropylmethyl-7-(2,4-difluoro-benzyl)-9-methyl-7,9-dihydro-2H-[1,2,4]triazolo[3,4-i]purine-3,8-dione (167), 4-amino-2-furan-2-yl-6-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-6H-8-oxa-1,3,3a,5,6-pentaaza-as-indacen-7-one (168), and 4-Amino-2-furan-2-yl-6-(2-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethyl)-8,8-dimethyl-6,8-dihydro-1,3,3a,5,6-pentaaza-as-indacen-7-one (169) 2. The pharmaceutical composition of claim 1, selected from the group consisting of:

5. A 2A / A 2B Pharmaceutical compositions for the treatment of conditions or disorders ameliorated by the inhibition of a receptor, comprising a compound of formula II and its pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof. 【Chemistry 2】 [In the formula, Y is selected from N or CR, and R is selected from H, hydroxy, alkoxy, alkyl, or aryl; R 1 is a group in which one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), with the proviso that the heteroatom is not adjacent to the N in the ring and p is selected from 0, 1 or 2, where alkyl, alkenyl and alkynyl are unsubstituted or are selected from alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO 3 H, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, -S(O) 2 NR a R a , -NR a S(O) 2 R a , or -S(O) p R a are independently substituted with R 2 is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, haloalkyl, haloalkyloxy, alkoxy, -NR b R b , -S(O) p R b , cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy, wherein alkyl, alkenyl, alkynyl, alkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, and R b is unsubstituted or is alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO 3 H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O) 2 NR c R c , -NR c S(O) 2 R c or -S(O) p R d and each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R 3 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, where alkyl, alkenyl, alkynyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl are unsubstituted or are selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO 3 H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O) 2 NR c R c , -NR c S(O) 2 R c or -S(O) p R d and each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from X is optionally substituted arylene or optionally substituted heteroarylene; A is a bond, 1 to 4 methylene groups are O, -S(O) p -, -N(R b )-, or —C(O)—, (C 1 ~C 6 ) alkylene, (C 2 ~C 6 ) alkenylene or (C 2 ~C 6 ) alkynylene groups, wherein alkylene, alkenylene, and alkynylene are unsubstituted or selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO 3 H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O) 2 NR c R c , -NR c S(O) 2 R c or -S(O) p R d and each substituent is unsubstituted or is selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF 3 , amino, substituted amino, cyano or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl, or heteroaryl, where heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO 3 H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O) 2 NR b R b , -NR b S(O) 2 R b or -S(O) p R d and each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R a are independently selected from hydrogen or alkyl; R b is independently selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl; R d is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; p is 0, 1 or 2].

6. 6. The pharmaceutical composition of claim 5 for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

7. 6. The pharmaceutical composition of claim 5, in combination with at least one PD-L1 antibody, for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

8. The compound of formula II is 8-(4-benzyloxy-phenyl)-1-propyl-1,7-dihydro-purin-6-one (170), 1-Propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (171), 8-(1-benzyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (170), 2-chloro-8-[1-(2,3-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (172), 2-chloro-8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (173), 2-chloro-1-propyl-8-[1-(4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (174), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (175), 8-[1-(2,3-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (176), 1-Propyl-8-[1-(4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (177), 1-Propyl-8-(1H-pyrazol-4-yl)-1,7-dihydro-purin-6-one (178), 2-chloro-8-[1-(3-fluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (179), 8-[1-(2,4-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (180), 2-chloro-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (181), 8-{4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy]-phenyl}-1-propyl-1,7-dihydro-purin-6-one (182), 8-{4-[5-oxo-1-(4-trifluoromethoxy-phenyl)-pyrrolidin-3-ylmethoxy]-phenyl}-1-propyl-1,7-dihydro-purin-6-one (183), 1-Propyl-8-{4-[3-(3-trifluoromethyl-phenyl)-prop-2-ynyloxy]-phenyl}-1,7-dihydro-purin-6-one (184), 8-{4-[5-oxo-1-(3-trifluoromethyl-phenyl)-pyrrolidin-3-ylmethoxy]-phenyl}-1-propyl-1,7-dihydro-purin-6-one (185), 2-chloro-8-[1-(2,4-difluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (186), 8-[1-(3-fluoro-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (187), 2-morpholin-4-yl-1-propyl-8-[1-(4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (188), N-(4-cyano-phenyl)-2-[4-(6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-phenoxy]-acetamide (189), [4-(6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-phenoxy]-acetic acid (190), 8-(1-benzyl-1H-pyrazol-4-yl)-2-chloro-1-propyl-1,7-dihydro-purin-6-one (191), 8-(4-{2-oxo-2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethoxy}-phenyl)-1-propyl-1,7-dihydro-purin-6-one (192), 8-(1-benzyl-1H-pyrazol-4-yl)-1-propyl-2-(4-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (193), 8-(1-benzyl-1H-pyrazol-4-yl)-1-propyl-2-(3-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (194), 8-(1-benzyl-1H-pyrazol-4-yl)-2-[2-(4-methoxy-phenyl)-ethylamino]-1-propyl-1,7-dihydro-purin-6-one (195), 8-(1-benzyl-1H-pyrazol-4-yl)-2-phenethylamino-1-propyl-1,7-dihydro-purin-6-one (196), 8-(1-benzyl-1H-pyrazol-4-yl)-2-(4-methyl-piperazin-1-yl)-1-propyl-1,7-dihydro-purin-6-one (197), 8-(1-benzyl-1H-pyrazol-4-yl)-2-piperidin-1-yl-1-propyl-1,7-dihydro-purin-6-one (198), 8-{1-[1-(2,4-difluoro-phenyl)-5-oxo-pyrrolidin-3-ylmethyl]-1H-pyrazol-4-yl}-1-propyl-1,7-dihydro-purin-6-one (199), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-2-(2-hydroxy-ethylamino)-1-propyl-1,7-dihydro-purin-6-one (200), 2-amino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (201), 8-(1-benzyl-1H-pyrazol-4-yl)-2-methylamino-1-propyl-1,7-dihydro-purin-6-one (202), [8-(1-benzyl-1H-pyrazol-4-yl)-6-oxo-1-propyl-6,7-dihydro-1H-purin-2-ylamino]-acetic acid ethyl ester (203), 8-(1-benzyl-1H-pyrazol-4-yl)-2-methoxy-1-propyl-1,7-dihydro-purin-6-one (204), 1,2-Dipropyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (205), 1-Propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-2-(4-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (206), 1-Propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (207), 2-(3-fluoro-phenyl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (208), 2-Dimethylamino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (209), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6-oxo-1-propyl-6,7-dihydro-1H-purine-2-carbonitrile (210), 8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6-oxo-1-propyl-6,7-dihydro-1H-purine-2-carboxylic acid (211), 8-(4-benzyloxy-phenyl)-1-propyl-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (212), 8-{4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy]-phenyl}-1-propyl-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (213), 8-(4-Methoxy-phenyl)-1-propyl-2-(3-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (214), 2-ethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (215), 2-benzyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (216), {6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-ylamino}-acetic acid (217), (S)-1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (218), 1-Propyl-2-pyrrolidin-1-yl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (219), 2-Methylamino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (220), 2-Cyclobutylamino-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (221), 2-chloro-8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-7-methyl-1-propyl-1,7-dihydro-purin-6-one (222), 2-Methoxy-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (223), 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carbonitrile (224), 2-Cyclopentyloxy-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (225), 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carboxylic acid amide (226), {6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yloxy}-acetic acid ethyl ester (227), 2-morpholin-4-yl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (228), {6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yloxy}-acetic acid (229), 8-{1-[3-(4-fluoro-phenyl)-prop-2-ynyl]-1H-pyrazol-4-yl}-1-propyl-2-pyrrolidin-1-yl-1,7-dihydro-purin-6-one (230), (S)-1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid amide (231), 1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-piperidine-3-carboxylic acid (232), 1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-piperidine-4-carboxylic acid (233), (2R,4R)-4-hydroxy-1-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (234), 2-(2,3-dihydroxy-propylamino)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (235), 2-(2-Methoxy-ethylamino)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (236), 2-(4-hydroxy-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (237), 2-(3-hydroxy-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (238), 2-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-ylamino}-ethanesulfonic acid (239), 2-(3-hydroxymethyl-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (240), (Methyl-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-amino)-acetic acid (241), 2-(2-hydroxy-ethylamino)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (242), 2-(4-hydroxymethyl-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (243), 2-(4-hydroxymethyl-piperidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (244), (S)-3-methyl-2-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-ylamino}-butyric acid (245), 2-((S)-2-Methoxymethyl-pyrrolidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (246), 2-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (247), 2-((R)-3-hydroxy-pyrrolidin-1-yl)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (248), 1-Propyl-2-(tetrahydro-pyran-4-ylamino)-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (249), 2-Fluoro-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (250), 1-Propyl-2-(2,2,2-trifluoro-ethoxy)-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (251), 2-(2-Methoxy-ethoxy)-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (252), 7-methyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (253), 2-chloro-1-propyl-8-[6-(3-trifluoromethyl-benzylamino)-pyridin-3-yl]-1,7-dihydro-purin-6-one (254), 2-chloro-8-[6-(3-fluoro-benzylamino)-pyridin-3-yl]-1-propyl-1,7-dihydro-purin-6-one (255), 1-Propyl-8-[6-(3-trifluoromethyl-benzylamino)-pyridin-3-yl]-1,7-dihydro-purin-6-one (256), 1-Propyl-8-(1-pyridin-3-ylmethyl-1H-pyrazol-4-yl)-1,7-dihydro-purin-6-one (257), 1-Propyl-8-[1-(6-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (258), 2-Cyclopropyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (259), 2-Difluoromethoxy-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (260), 1-Propyl-2-trifluoromethyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (261), 2-chloro-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (262), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (263), 2-Isobutylamino-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (264), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-pyrrolidin-1-yl-1,7-dihydro-purin-6-one (265), 2-[2-(4-methoxy-phenyl)-ethylamino]-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (266), 2-(4-methyl-piperazin-1-yl)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (267), 2-[4-(4-fluoro-phenyl)-piperazin-1-yl]-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (268), 1-[8-(1-methyl-1H-pyrazol-4-yl)-6-oxo-1-propyl-6,7-dihydro-1H-purin-2-yl]-pyrrolidine-2-carboxylic acid methyl ester (269), 2-benzyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (270), 2-(3-fluoro-phenyl)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (271), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-(4-trifluoromethyl-phenyl)-1,7-dihydro-purin-6-one (272), 8-(1-methyl-1H-pyrazol-4-yl)-2-phenethylamino-1-propyl-1,7-dihydro-purin-6-one (273), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-(4-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (274), 2-Cyclopropylamino-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (275), 2-(3-fluoro-phenoxy)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (276), 2-(4-Methoxy-phenylamino)-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (277), 7-benzyl-2-chloro-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (278), 9-benzyl-2-chloro-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,9-dihydro-purin-6-one (279), 2-amino-7-benzyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (280), 2-chloro-8-furan-2-yl-1-propyl-1,7-dihydro-purin-6-one (281), 2-amino-8-[1-(4-fluoro-benzyl)-1H-imidazo[1,2-b]pyrazol-7-yl]-1-propyl-1,7-dihydro-purin-6-one (282), 2-chloro-8-[1-(4-fluoro-benzyl)-1H-imidazo[1,2-b]pyrazol-7-yl]-1-propyl-1,7-dihydro-purin-6-one (283), 2-amino-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (284), 2-amino-7-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (285), 2-amino-9-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,9-dihydro-purin-6-one (286), 7-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (287), 9-methyl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,9-dihydro-purin-6-one (288), 2-amino-8-furan-2-yl-1-propyl-1,7-dihydro-purin-6-one (289), 2-chloro-8-furan-2-yl-7-methyl-1-propyl-1,7-dihydro-purin-6-one (290), 8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-2-(3-trifluoromethyl-benzylamino)-1,7-dihydro-purin-6-one (291), 2-furan-2-yl-8-(1-methyl-1H-pyrazol-4-yl)-1-propyl-1,7-dihydro-purin-6-one (292), 8-(1-benzyl-1H-pyrazol-4-yl)-2-furan-2-yl-1-propyl-1,7-dihydro-purin-6-one (293), 2-chloro-8-(6-chloro-pyridin-3-yl)-1-propyl-1,7-dihydro-purin-6-one (294), 2-Difluoromethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (295), 2-Fluoromethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (296), 2-Fluoromethyl-8-{1-[3-(3-methoxy-phenyl)-prop-2-ynyl]-1H-pyrazol-4-yl}-1-propyl-1,7-dihydro-purin-6-one (297), 2-Difluoromethyl-8-{1-[2-oxo-2-(4-m-tolyl-piperazin-1-yl)-ethyl]-1H-pyrazol-4-yl}-1-propyl-1,7-dihydro-purin-6-one (298), 3-Fluoro-N-methyl-N-[5-(6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-benzamide (299), N-[5-(2-difluoromethyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-N-methyl-benzamide (300), N-[5-(2-difluoromethyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (301), 2-Fluoromethyl-1-propyl-8-[1-(5-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (302), 2-Fluoromethyl-1-propyl-8-[1-(2-trifluoromethyl-pyridin-4-ylmethyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (303), 2-Fluoromethyl-8-[3-(3-methoxy-phenoxy)-isoxazol-5-yl]-1-propyl-1,7-dihydro-purin-6-one (304), 2-Difluoromethyl-8-{3-[3-(3-fluoro-phenyl)-prop-2-ynyloxy]-isoxazol-5-yl}-1-propyl-1,7-dihydro-purin-6-one (305), 2-Fluoromethyl-1-(2-hydroxy-ethyl)-8-[3-(3-methoxy-phenoxy)-isoxazol-5-yl]-1,7-dihydro-purin-6-one (306), 2-Difluoromethyl-1-ethyl-8-{3-[3-(3-fluoro-phenyl)-prop-2-ynyloxy]-isoxazol-5-yl}-1,7-dihydro-purin-6-one (307), 2-Difluoromethyl-1-ethyl-8-(1-{2-[4-(3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-1H-pyrazol-4-yl)-1,7-dihydro-purin-6-one (308), 1-ethyl-8-(1-{2-[4-(3-methoxy-phenyl)-piperazin-1-yl]-2-oxo-ethyl}-1H-pyrazol-4-yl)-6-oxo-6,7-dihydro-1H-purine-2-carbonitrile (309), N-[5-(2-cyano-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (310), N-{5-[2-cyano-1-(2-hydroxy-ethyl)-6-oxo-6,7-dihydro-1H-purin-8-yl]-pyridin-2-yl}-3-methoxy-benzenesulfonamide (311), 2-Difluoromethyl-1-ethyl-8-{4-[3-(3-methoxy-phenyl)-prop-2-ynyloxy]-phenyl}-1,7-dihydro-purin-6-one (312), 2-Difluoromethyl-1-ethyl-8-{4-[1-(3-fluoro-phenyl)-5-oxo-pyrrolidin-3-ylmethoxy]-phenyl}-1,7-dihydro-purin-6-one (313), 2-Difluoromethyl-8-[5-(3-methoxy-phenoxy)-1-methyl-1H-pyrazol-3-yl]-1-propyl-1,7-dihydro-purin-6-one (314), 2-Difluoromethyl-8-{5-[1-(3-methoxy-phenyl)-piperidin-4-yloxy]-1-methyl-1H-pyrazol-3-yl}-1-propyl-1,7-dihydro-purin-6-one (315), 2-Fluoromethyl-8-{3-[1-(3-fluoro-phenyl)-piperidin-4-yloxy]-isoxazol-5-yl}-1-propyl-1,7-dihydro-purin-6-one (316), 1-ethyl-8-{6-[1-(3-fluoro-phenyl)-5-oxo-pyrrolidin-3-ylmethoxy]-pyridin-3-yl}-6-oxo-6,7-dihydro-1H-purine-2-carbonitrile (317), 1-ethyl-8-{6-[1-(3-methoxy-phenyl)-pyrrolidin-3-yloxy]-pyridin-3-yl}-6-oxo-6,7-dihydro-1H-purine-2-carbonitrile (318), 3-[4-(2-difluoromethyl-1-ethyl-6-oxo-6,7-dihydro-1H-purin-8-yl)-pyrazol-1-ylmethyl]-benzoic acid (319), 2-Difluoromethyl-1-ethyl-8-[1-(3-hydroxymethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (320), 2-Difluoromethyl-3-ethyl-6-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (321), N-[5-(2-cyano-4-oxo-3-propyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-6-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (322), 2-fluoromethyl-6-{3-[1-(3-fluoro-phenyl)-piperidin-4-yloxy]-isoxazol-5-yl}-3-propyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (323), 2-Difluoromethyl-6-{5-[1-(3-methoxy-phenyl)-piperidin-4-yloxy]-1-methyl-1H-pyrazol-3-yl}-3-propyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (324), 3-ethyl-6-{6-[1-(3-methoxy-phenyl)-pyrrolidin-3-yloxy]-pyridin-3-yl}-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-2-carbonitrile (325), 2-Fluoromethyl-6-{3-[1-(3-fluoro-phenyl)-piperidin-4-yloxy]-isoxazol-5-yl}-7-hydroxy-3-propyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (326), 2-Difluoromethyl-3-ethyl-6-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-7-methyl-3,5-dihydro-pyrrolo[3,2-d]pyrimidin-4-one (327), 2-Difluoromethyl-1-ethyl-8-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-7-methyl-1,7-dihydro-purin-6-one (328), N-[5-(2-cyano-7-methyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyridin-2-yl]-3-methoxy-benzenesulfonamide (329), 1-(2,2-difluoro-ethyl)-2-ethyl-8-[1-(3-methoxy-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (330), 3-{3-[4-(2-difluoromethyl-6-oxo-1-propyl-6,7-dihydro-1H-purin-8-yl)-pyrazol-1-yl]-prop-1-ynyl}-benzoic acid (331), 3-(3-{4-[1-(2,2-difluoro-ethyl)-2-ethyl-6-oxo-6,7-dihydro-1H-purin-8-yl]-pyrazol-1-yl}-prop-1-ynyl)-benzoic acid (332), 3-{3-[4-(6-oxo-1-propyl-2-trifluoromethyl-6,7-dihydro-1H-purin-8-yl)-pyrazol-1-yl]-prop-1-ynyl}-benzoic acid (333), and 6-Oxo-1-propyl-8-[6-(3-trifluoromethyl-benzyl)-pyridin-3-yl]-6,7-dihydro-1H-purine-2-carbonitrile (334) 6. The pharmaceutical composition of claim 5, selected from the group consisting of:

9. A 2A / A 2B Pharmaceutical compositions for the treatment of conditions or disorders ameliorated by the inhibition of a receptor, comprising a compound of formula III or IV and pharmaceutically acceptable salts, analogs, tautomeric forms, stereoisomers, geometric isomers, polymorphs, hydrates, solvates, metabolites, and prodrugs thereof. 【Transformation 3】 [In the formula, R 1 is a group in which one or more methylene groups are substituted with a heteroatom or -O-, -S(O)p-, -N(R a )-, or -C(O), provided that the heteroatom is not adjacent to the N in the ring and p is selected from 0, 1 or 2; wherein alkyl is unsubstituted or substituted with alkoxy, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, haloalkyl, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -aminocarbonylamino, hydroxyamino, alkoxyamino; R 2 is hydrogen, halogen, cyano, nitro, carboxy, acyl, aminocarbonyl, alkyl, alkenyl, alkynyl, hydroxyalkyl, carboxyalkyl, haloalkyl, haloalkyloxy, alkoxy, -NR b R b , -S(O) p R b , cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, and heteroaryloxy, wherein alkyl, alkenyl, alkynyl, alkoxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, arylalkyl, aryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, and R b is unsubstituted or is alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, nitro, amino, monoalkylamino, dialkylamino, hydroxyamino, alkoxyamino, aminocarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, -SO 3 H, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, cycloalkyl, cycloalkyloxy, cycloalkenyl, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, -S(O) 2 NR c R c , -NR c S(O) 2 R c or -S(O) p R d and each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from R' and R" are independently selected from hydrogen or alkyl; or R' and R" together can represent O or a saturated or partially unsaturated lower cycloalkyl ring system; R 3 is alkyl, aryl, -C(O)R 4 and -P(O)(OR 5 ) 2 is selected from the group consisting of R 4 is alkyl, alkoxy, aryl, heteroaryl, heterocyclyl, or -NR 6 R 7 is selected from R 5 is hydrogen, alkyl, aryl, arylalkyl, -CH 2 OC(O) alkyl or -CH 2 OC(O)Oalkyl, or two R 5 the groups taken together form a 5- or 6-membered ring system which is saturated or partially unsaturated and optionally substituted with 1 to 4 substituents independently selected from halo, alkyl, aryl, or heteroaryl; R 6 and R 7 is independently selected from the group consisting of hydrogen, alkyl, heterocyclyl, and heterocyclylalkyl; or R 6 and R 7 together form a monocyclic ring system that is saturated or partially unsaturated and optionally has an additional heteroatom selected from O, N, or S, wherein the ring system is not substituted with a halo, alkyl, alkoxy, or -NR 8 R 9 and optionally substituted with 1 to 4 substituents independently selected from R 4 , R 5 , R 6 and R 7 is hydroxyl, halogen, alkyl, alkoxy, haloalkyl, -NR 8 R 9 , -C(O)OR 10 , -OC(O)R 10 or -NC(O)R 10 and optionally substituted with 1 to 4 substituents independently selected from R 8 and R 9 are independently selected from the group consisting of hydrogen and alkyl; R 10 is selected from hydrogen, hydroxy, halogen, amino, substituted amino, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, carboxy, carboxyalkyl, aminocarbonyl, aryl, or arylalkyl; X is optionally substituted arylene or optionally substituted heteroarylene; A is a bond or 1 to 4 methylene groups are O, -S(O) p -, -N(R b )-, or —C(O)—, optionally replaced by a group independently selected from (C 1 ~C 6 ) alkylene, wherein alkylene is unsubstituted or is selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO 3 H, aryl, aryloxy, cycloalkyloxy, heteroaryl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, S(O) 2 NR c R c , -NR c S(O) 2 R c or -S(O) p R d are independently substituted with Each substituent may be unsubstituted or may be selected from the group consisting of alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF 3 , amino, substituted amino, cyano or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from B is selected from hydrogen, heterocyclyl, cycloalkyl, aryl, or heteroaryl, where heterocyclyl, cycloalkyl, aryl, and heteroaryl are unsubstituted or are selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino, monoalkylamino, dialkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocyclylamino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, hydroxyalkyl, keto, thiocarbonyl, carboxy, alkylcarboxy, carboxyalkyl, carboxyalkyloxy, alkylcarboxyalkyloxy, -SO 3 H, aryl, arylalkyl, aryloxy, cycloalkyloxy, heteroaryl, heteroarylalkyl, aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, hydroxyamino, alkoxyamino, nitro, -S(O) 2 NR b R b , -NR b S(O) 2 R b or -S(O) p R d and each substituent is unsubstituted or is independently substituted with alkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, alkoxyalkoxy, alkoxyalkyl, halogen, haloalkyl, haloalkoxy, amino, substituted amino, cyano, or -S(O) p R d and is substituted with 1, 2, or 3 substituents independently selected from D is -O-, -S(O)p-, or -N(R a )-selected from R a is hydrogen or alkyl, R b is selected from the group consisting of hydrogen, alkyl, acyl, carboxyalkyl, carbonylamino, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl; R c is selected from hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl; R d is selected from alkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl; p is 0, 1 or 2; t is 1 or 2].

10. 10. The pharmaceutical composition of claim 9 for use in the treatment of a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

11. 10. The pharmaceutical composition of Claim 9, in combination with at least one PD-L1 antibody, for use in treating a condition or disorder selected from prostate cancer, rectal cancer, renal cancer, ovarian cancer, endometrial cancer, thyroid cancer, pancreatic cancer, breast cancer, colon cancer, bladder cancer, brain cancer, glial cancer, melanoma cancer, pineal cancer, or lung cancer.

12. The compound of formula III or formula IV is phosphoric acid mono-{2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (335), mono-{2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl}phosphate disodium salt (336), phosphoric acid mono-{2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (337), phosphoric acid mono-{2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl} ester (338), 2,2-Dimethyl-propionic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (339), 2,2-Dimethyl-propionic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (340), 2,2-Dimethyl-propionic acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (341), 7-Methoxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (342), 9-Methoxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,9-dihydro-purin-6-one (343), 2-chloro-7-methoxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (344), phosphoric acid mono-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (345), (2-Dimethylamino-ethyl)-methyl-carbamic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (346), (1-Ethyl-pyrrolidin-2-ylmethyl)-carbamic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (347), Nicotinic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (348), Acetic acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (349), Butyric acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (350), Butyric acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (351), Nicotinic acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (352), (2-Dimethylamino-ethyl)-methyl-carbamic acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (353), (2-Dimethylamino-ethyl)-methyl-carbamic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (354), Butyric acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (355), 2,2-Dimethyl-propionic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (356), Nicotinic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (357), 4-Methyl-piperazine-1-carboxylic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (358), 1-{6-oxo-7-phosphonooxymethyl-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (359), 1-{7-(2,2-dimethyl-propionyloxymethyl)-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purin-2-yl}-pyrrolidine-2-carboxylic acid (360), 2,2-Dimethyl-propionic acid 2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (361), mono-{2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl}phosphate (362), phosphoric acid mono-{2-chloro-6-oxo-1-propyl-8-[1-(6-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (363), phosphoric acid mono-{6-oxo-1-propyl-8-[1-(6-trifluoromethyl-pyridin-3-ylmethyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (364), Benzoic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (365), 7-Methoxymethyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carbonitrile (366), Acetic acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester (367), (S)-Pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-{2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl} ester (368), Butyric acid 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (369), Butyric acid 2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (370), Butyric acid 2-chloro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (371), Butyric acid 6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl ester (372), phosphoric acid mono-{2-fluoro-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl} ester (373), mono-{6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl}phosphate (374), or Mono-{2-cyclopropyl-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-9-ylmethyl}phosphate (375) 10. The pharmaceutical composition of claim 9, selected from the group consisting of:

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