Use of substituted benzoxazole and benzofuran compounds for treatment and prevention of diseases associated with chronic fatigue, fatigue and / or fatigue intolerance

Abstract

The present invention relates to a substance (PDE7 inhibitor) having phosphodiesterase 7 inhibitory activity, such as spiro [[1, 3] oxazolo [5, 4-f] quinazoline-9, 10-dihydro-9, 10-dihydro-9, 10-dihydro-9, 10-dihydro-9, 10-dihydro-9, 10- The present invention relates to the use of 1, 1 '-cyclohexane]-7-one derivatives as active ingredients in therapeutic agents having phosphodiesterase 7 inhibitory activity, using PDE7 inhibitors alone or in combination with other therapeutic agents for the treatment and prevention of various diseases, syndromes, disease states or conditions associated with chronic fatigue, fatigue and / or fatigue intolerance.

Description

Technical Field

[0001] The present invention relates to the use of substances with phosphodiesterase-7 inhibitory activity (PDE7 inhibitors) as active ingredients in therapeutic agents with phosphodiesterase-7 inhibitory activity, using PDE7 inhibitors alone or in combination with other therapeutic agents for the treatment and prevention of different diseases, syndromes, disease states or conditions associated with chronic fatigue, exhaustion and / or exertion intolerance. These diseases, syndromes, disease states or conditions will be covered by the term "diseases associated with chronic fatigue" and abbreviated as (DACF), which include diseases diagnosed as follows: myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS), systemic exertion intolerance, exertion intolerance, long-term COVID condition, post-Covid-19 syndrome (PCS), acute post-Covid syndrome (PACS), acute sequelae of SARS-CoV-2 infection (PASC), COVID-19 vaccination (Long Vax) and vaccinations against other bacteria, viruses, and pathogenic agents, and post-vac-syndrome following viral, bacterial, or fungal infections, and post-infectious fatigue following viral, bacterial, or fungal infections, particularly ME / CFS of non-infectious, non-inflammatory, and non-immune causes, cancer-related fatigue (in which chronic fatigue and exhaustion are symptoms of or associated with cancer), and fatigue associated with fibromyalgia, Ehlers-Danlos syndrome, Marfan syndrome, Gulf War illness, and the autoimmune diseases rheumatoid arthritis, ANCA vasculitis (antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis), and Sjögren's syndrome ( syndrome, and other autoimmune diseases with debilitating symptoms of fatigue and exhaustion. Background Art

[0002] PDE7 inhibitors are known and treatment methods have been described in the context of inflammation, immunomodulation, tumor diseases related to the immune system, respiratory diseases, cardiovascular diseases (acute myocardial infarction, stroke), neurodegenerative diseases (multiple sclerosis, Alzheimer's disease, Parkinson's disease), other neurological diseases (spinal cord injuries, schizophrenia) and withdrawal from different addictions, for example in US 11,207,275, US 8,846,654. The claim to treat neurodegenerative diseases and neurological diseases is based on the assumption that PDE7 inhibition has an anti-inflammatory effect and treats autoimmune mechanisms in the nervous system.

[0003] The pathophysiology of diseases associated with chronic fatigue (DACF) has remained mysterious, thus preventing the derivation or development of rational pharmacological or therapeutic strategies. Therefore, due to the lack of understanding of these diseases and their pathophysiology, there are currently no specific and effective treatments.

[0004] The present invention has been established by a unified and comprehensive disease hypothesis elaborated by the inventors, who found that DACF can stimulate the sodium-potassium ATPase (Na + / K + The present inventors have found that the increase of cAMP (cyclic adenosine monophosphate) in skeletal muscle (myocytes) caused by PDE7 inhibition will stimulate the sodium-potassium ATPase (Na + / K + ATPase) to prevent intracellular sodium (Na + ) and subsequent intracellular and mitochondrial calcium (Ca 2+ ), which plays a strong pathophysiological role in the onset and persistence of chronic fatigue, exhaustion and / or exertion intolerance. A second transporter that is equally important for preventing mitochondrial calcium overload is the mitochondrial sodium calcium exchanger (abbreviated as NCLX), which exports calcium from the mitochondria in exchange for sodium, thereby limiting and preventing mitochondrial calcium overload. cAMP also stimulates the activity of NCLX. Therefore, the increase in cAMP caused by PDE7 inhibition has a synergistic effect on both ion transporters, preventing cellular and mitochondrial calcium overload and damage. The increase in cAMP can be achieved by administering a PDE7 inhibitor, which inhibits the hydrolysis of cAMP to increase its level. In addition, the increase in cAMP caused by PDE7 inhibition also occurs in the blood vessels of skeletal muscle and the brain, and enhances organ blood flow to further improve it. Since the expression of the PDE7A variant in skeletal muscle is much higher than that of the variant PDE7B, a PDE7 inhibitor with a particularly strong inhibitory effect on PDE7A is preferred.

[0005] To date, 11 families of phosphodiesterases (PDEs) have been identified. They differ in their primary structure, their substrate specificity, and their sensitivity to various effectors and inhibitors of PDE specificity. Each family consists of one or more genes that are expressed in various tissues in the form of splice variants. For example, PDE4, PDE7, and PDE8 specifically hydrolyze cAMP, and PDE5, PDE6, and PDE9 specifically hydrolyze cGMP.

[0006] Family PDE7 is represented by the following: subtype PDE7A with their variants PDE7A1, PDE7A2 and PDE7A3, and subtype PDE7B with their variants PDE7B1, PDE7B2 and PDE7B3, which are derived from two different genes. PDE7 is highly selective for cAMP. The Michaelis constant K of PDE7B for cAMP m The values ​​ranged from 0.13 μM to 0.2 μM. The K of PDE7A1 and PDE7A2 for cAMP mThe values ​​are 0.2 μM and 0.1 μM, respectively. The catalytic part of PDE7B shows about 70% homology with the catalytic part of PDE7A.

[0007] In summary, inhibition of PDE7 will only elevate cAMP, and the effects of PDE7 inhibitors are largely limited to tissues expressing PDE7.

[0008] It is known that PDE7 isozymes are present in skeletal muscle (in myocytes), with higher expression of PDE7A variants compared to PDE7B variants. Inhibition of PDE7 by appropriate inhibitors increases the concentration of the second messenger cAMP, which is a key second messenger for the normal function of skeletal muscle. Another importance in treating DACF is the presence of PDE7 in blood vessels. Inhibition of PDE7 in blood vessels increases cAMP, which has a vasodilation effect and improves organ blood flow, thereby improving metabolic conditions and performance. In short, increasing cAMP in skeletal muscle (myocytes) and in blood vessels supplying skeletal muscle and the brain will improve or cure DACF or prevent relapses after infection or prevent chronic fatigue, exhaustion and / or intolerance to exertion. Due to the tissue distribution of PDE7, in particular its expression in skeletal muscle (myocytes), and its role in degrading cAMP in skeletal muscle (myocytes) and blood vessels of skeletal muscle and brain, PDE7 inhibitors can treat and prevent DACF diseases with minimal side effects.

[0009] Among the diseases associated with fatigue, exhaustion and / or exertion intolerance, myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS) is the most debilitating condition. Although ME / CFS frequently affects about 0.3% of the population even before Covid-19, most physicians are not familiar with it. ME / CFS is characterized by extreme fatigue, post-exertional malaise (PEM), exertion intolerance, cognitive dysfunction, orthostatic intolerance including postural tachycardia (POTS) and is associated with a variety of different symptoms including muscle weakness and pain. Despite the fact that unrefreshing sleep is also a typical symptom and that unrefreshing sleep may worsen the patient's condition, sleep disorders are not the initial cause of extreme fatigue and exhaustion, but rather a consequence of ME / CFS that may further worsen the condition.

[0010] Prior to the present invention, no specific treatment was available, and current symptomatic treatments can only provide some symptom relief, not a cure. Many patients with ME / CFS are bedridden or in wheelchairs; most patients are unable to work. ME / CFS is often, but not always, triggered by various viral infections, such as Epstein–Barr virus (EBV), enterovirus, influenza virus, dengue fever, and, as a recent example, coronavirus (SARS-CoV-2). Persistent or emerging illnesses after past acute coronavirus infections are known as long-term COVID or post-Covid-19 syndrome (PCS) or post-acute Covid syndrome (PACS) or post-acute sequelae of SARS-CoV-2 infection (PASC). Studies on PCS have shown that the symptomatology and mechanisms of the two conditions have the widest overlap. A small proportion of PCS patients present with the full picture of ME / CFS. ME / CFS patients and ME / CFS patients with PCS show indistinguishable symptomatology with respect to symptoms in the orthostatic tolerance test and decreased cerebral blood flow. The prevalence of ME / CFS is expected to be strongly increased by Covid-19.

[0011] Therefore, there is a strong need for drugs or therapeutic agents that can be used to treat and prevent chronic fatigue, exhaustion and / or exertion intolerance associated with various diseases, syndromes, disease states (DACF).

[0012] Clearly, there is a strong need in the art for new approaches to treat and prevent chronic fatigue, exhaustion and / or exertion intolerance associated with various diseases, syndromes, condition (DACF). Summary of the invention

[0013] The present invention provides a novel approach for treating and preventing DACF by using a substance having phosphodiesterase-7 inhibitory activity (PDE7 inhibitor) as an active ingredient in a therapeutic agent having phosphodiesterase-7 inhibitory activity. DETAILED DESCRIPTION

[0014] The term "PDE7 inhibitor" used in this application includes chemical compounds, proteins or polypeptides, nucleic acids, ribozymes, DNA enzymes, protein degraders, gene therapy, or other such agents, which directly or indirectly inhibit or block the phosphodiesterase 7 activity of PDE7 proteins (PDE7A, PDE7B) in a selective or non-selective manner. In some cases, the agent can directly bind to the PDE7 protein or directly interact with the PDE7 protein. The agent bound to PDE7 can be used to inhibit or block PDE7 activation by any suitable means (e.g., by inhibiting the binding of cAMP or substrate ligands to PDE7). In other cases, the PDE7 inhibitor can indirectly inhibit PDE7 activity, for example, by reducing the expression of PDE7 protein. In some cases, the PDE7 inhibitor can inhibit PDE7 activity by changing the cellular distribution of PDE7 (e.g., by interfering with the binding between PDE7 and intracellular anchoring proteins).

[0015] The term chronic fatigue-related diseases as used herein includes various diseases, syndromes, disease states, or conditions associated with chronic fatigue, exhaustion, and / or exertion intolerance. These include myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS), systemic exertion intolerance, exertion intolerance, long-term COVID illness, post-Covid-19 syndrome (PCS), post-acute Covid syndrome (PACS), post-acute sequelae of SARS-CoV-2 infection (PASC), post-vaccination syndrome (post-vac-syndrome) following COVID-19 vaccination and vaccination against other bacteria, viruses, and pathogenic agents, and post-infectious fatigue and exhaustion following viral, bacterial, or fungal infections, particularly ME / CFS of non-infectious, non-inflammatory, and non-immune causes. In addition, the term includes diseases in which chronic fatigue and exhaustion are symptoms of or associated with cancer (cancer-related fatigue), fibromyalgia, Ehlers-Danlos syndrome, Marfan syndrome, Gulf War illness, the autoimmune diseases rheumatoid arthritis, ANCA vasculitis and Sjögren's syndrome, and other autoimmune diseases with fatigue and exhaustion as debilitating symptoms. Hereinafter, these diseases, syndromes, disease states or conditions are encompassed by diseases associated with chronic fatigue (DACF).

[0016] In a preferred embodiment of the present invention, the PDE7 inhibitor is a compound that is potent enough to be effective at IC 50 <50 μM, preferably less than or about 1 μM, inhibits the enzymatic activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B). Even more preferably, the PDE7 inhibitor is potent enough to inhibit the enzymatic activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) with an IC 50Inhibits the enzymatic activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) at about 0.1 to about 600 nM, in particular, the PDE7 inhibitor is potent so as to have an IC 50 From about 0.2 to about 100 nM, preferably with IC 50 The enzyme activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) is inhibited at about 1 to about 100 nM.

[0017] In the present invention, PDE7 inhibitors stimulate Na + / K + -ATPase and NCLX to prevent adverse ionic changes that cause mitochondrial and energy dysfunction in skeletal muscle. Sodium (Na + ) and subsequent harmful increases in calcium (Ca 2+ ) is caused by the stimulation of Na by PDE7 inhibition + / K + -ATPase and NCLX inhibition. PDE7 inhibition has a dual effect by preventing sodium (Na + ) and improves the energy status of skeletal muscle by preventing subsequent adverse changes in cellular and mitochondrial calcium and by improving blood flow to the muscle. In addition, PDE7 inhibition improves metabolic status and performance by increasing cerebral blood flow, thereby improving the energy status of the brain, and can reduce neuroinflammation in the brain through its action via cAMP. Neuroinflammation is believed to play a pathophysiological role in central nervous system disorders that lead to autonomic dysfunction, impaired cognition and other CNS symptoms.

[0018] The improvement of skeletal muscle energy status caused by PDE7 inhibition prevents the release of vasoactive pain (pain) mediators in skeletal muscle. Usually, these mediators are released to compensate for poor metabolic status, and physiologically only work locally in skeletal muscle. Because the metabolic status in the large muscles of the body is very poor and over-produced in disease states, overflowing into the systemic circulation, these mediators with pain properties can reach and act on every organ of the body. These mediators cause a lot of the most different symptoms. In addition to fatigue and exhaustion, related symptoms also include brain fog, impaired cognition, disturbed sleep, orthostatic intolerance, muscle weakness, pain, post-exercise malaise (PEM), which is an aggravation of typical symptoms after low-intensity or moderate-intensity exercise, and many other diseases.

[0019] Through these combined beneficial effects, PDE7 inhibition improves the symptoms of DACF and may cure the disease of DACF, prevent relapses, and prevent the disease in a prophylactic manner.

[0020] Specific examples of PDE7 inhibitors for use in the present invention are the substances described below, which have Formula 1A, Formula 1B, Compound 1, Compound 2, Formula 2A, Formula 2B, Formula 2C, Compound 3, Formula 3, Compound 4, Formula 4A, Formula 4B, Formula 5, Formula 6, Formula 6A, Formula 6B, Formula 6C, Formula 6D, Formula 6E, Formula 6F, Formula 6G, Formula 6H, Formula 7A, Formula 7B, Formula 8, Formula 8A, Formula 9, Formula 10, Formula 11, Formula 12, Formula 13, Formula 14, Formula 15A, Formula 15B, Formula 16, Formula 16A, Formula 17A, Formula 17B, Formula 18, Formula 19, Formula 20, Formula 21, Formula 22, Formula 23, Formula 24, Formula 25, Formula 26, Formula 27A, Formula 27B, Formula 27C, Formula 27D, Formula 28, Formula 29, Formula 30, Formula 31, Formula 32, Formula 33, Formula 34, Formula 35, Formula 35A, Formula 36, Formula 37, Formula 38, Formula 39, Formula 40, Formula 41, Formula 42, Formula 42A, Formula 43A, Formula 43B, Formula 44, Formula 44A, Formula 44B, Formula 45, Formula 46, Formula 47, Formula 48, Formula 49, Formula 50, Formula 51, Formula 52, Formula 53, Formula 54, Formula 55, Formula 55A, Formula 55B, Formula 55C, Formula 55D, Formula 55E, Formula 55F, Formula 55G, Formula 55H, Formula 55I , Formula 55J, Formula 56, Formula 56B, Formula 56C, Formula 56D, Formula 56E, Formula 56F, Formula 56G, Formula 56H, Formula 57, Formula 57A, Formula 57B, Formula 57C, Formula 57D, Formula 57E, Formula 58, Formula 59, Formula 60, Formula 61, Formula 62, Formula 63, Formula 63A, Formula 64, dipyridamole, pentoxifylline, SUN11817, S14, S.14, and IBMX.

[0021] Methods of using PDE7 inhibitors to treat and prevent disorders associated with chronic fatigue (DACF):

[0022] Thus, the present invention includes methods of treating or preventing DACF comprising administering one or more PDE7 inhibitors to a subject having or at risk of developing DACF.

[0023] As used herein, unless the context clearly indicates otherwise, "treat" and similar words such as "treatment" or "treating" are a method of obtaining beneficial or desired results (including and preferably clinical results). Treatment may optionally include reducing or ameliorating a disease or condition such as DACF, or delaying the progression of a disease or condition such as DACF.

[0024] As used herein, unless the context clearly indicates otherwise, "prevent" and similar words such as "prevention", "preventing", etc., are methods of preventing the onset or recurrence of a disease or condition (e.g., DACF) or preventing the recurrence of a disease or condition, for example, after a viral infection such as Epstein-Barr virus infection, or preventing the recurrence of symptoms of a disease or condition, or optionally a method of delaying the onset or recurrence of a disease or condition or delaying the appearance or recurrence of symptoms of a disease or condition.

[0025] As used herein, the term "PDE7" is used generically to refer to all translation products encoded by transcripts of one or both of the following two genes: PDE7A and / or PDE7B.

[0026] As used herein, an "effective amount" or "therapeutically effective amount" of a substance such as a PDE7 inhibitor is an amount sufficient to affect a desired biological or psychological effect (e.g., a beneficial outcome, including a clinical outcome). For example, in the context of treating DACF using the methods of the present invention, an effective amount of a PDE7 inhibitor is an amount sufficient to treat and prevent DACF. Typically, an effective amount of a PDE7 inhibitor is provided to a subject.

[0027] Pharmaceutical composition, route of administration, unit dosage form, kit:

[0028] The composition of the present invention can be applied to a subject as a pharmaceutical composition or preparation. In a particular embodiment, the pharmaceutical composition of the present invention can be any form that allows the composition to be administered to a subject. For example, the composition can be in the form of a solid, a liquid, or a gas (aerosol). Typical routes of administration include, but are not limited to, oral administration, topical administration, parenteral administration, sublingual administration, rectal administration, vaginal administration, and nasal administration. The term parenteral as used herein includes subcutaneous injection, intravenous injection, intramuscular injection, epidural injection, intrasternal injection or infusion technology.

[0029] The pharmaceutical compositions used according to the present invention comprise: a PDE7 inhibitor, another therapeutic agent, and a pharmaceutically acceptable diluent, excipient, or carrier.

[0030] "Pharmaceutically acceptable carriers" for therapeutic use are well known in the pharmaceutical art. For example, sterile saline and phosphate buffered saline at physiological pH can be used. Preservatives, stabilizers, dyes, and even flavoring agents can be provided in the pharmaceutical composition. For example, sodium benzoate, sorbic acid, and esters of p-hydroxybenzoic acid can be added as preservatives. In addition, antioxidants and suspending agents can be used.

[0031] The pharmaceutical compositions of the present invention are typically formulated so as to allow the active ingredients contained therein to be bioavailable when the composition is administered to a subject. The composition to be administered to a subject can take the form of one or more dosage units, wherein, for example, a tablet, capsule, or cachet can be a single dosage unit, and a container containing a combination of agents according to the present invention in aerosol form can accommodate multiple dosage units. In a particular embodiment, the composition comprising a PDE7 inhibitor and ultimately another therapeutic agent is administered in one or more doses of a tablet formulation, typically orally. The tablet formulation can be, for example, an immediate release formulation, a controlled release formulation, or a sustained release formulation. In one embodiment, the tablet formulation comprises an effective amount of a composition containing a PDE7 inhibitor and ultimately another therapeutic agent. In a particular embodiment, the tablet comprises about 1 mg, 5 mg, 10 mg, 20 mg, 30 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of a PDE7 inhibitor and, if used in combination, a final amount of about 1 mg, 5 mg, 10 mg, 20 mg, 30 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of another therapeutic agent.

[0032] As an example, a unit administration form of a compound according to the invention in the form of a tablet may contain the following components: 50 mg of a compound having formula 55E, 223.75 mg of mannitol, 6 mg of croscarmellose sodium, 15 mg of corn starch, 2.25 mg of hydroxypropylmethylcellulose, and 3 mg of magnesium stearate.

[0033] Alternatively, according to the present invention, a capsule formulation may contain, for example, 50 mg of a compound having formula 55E 50 and a pharmaceutically acceptable excipient, wherein the excipient may contain one or more selected from the following substances: a disintegrant, a filler and a lubricant, and may contain an effective amount of a binder.

[0034] Preferably, the PDE7 inhibitor is provided to the subject in an amount ranging from 0.1-1000 mg / day, 1-1000 mg / day, 10-100 mg / day, or 25-50 mg / day.

[0035] Some combinations of PDE7 inhibitors and other therapeutic agents may not be easily adapted to a cocktail. For example, one of the agents may be more suitable for intravenous administration, while the other agent may be more suitable for oral administration. Alternatively, the serum half-life of the two agents may make it necessary to administer one of the agents more frequently than the other agent. Therefore, the present invention proposes a kit comprising one or more unit dosage forms of a PDE7 inhibitor and one or more unit dosage forms of another therapeutic agent, so that the two unit dosage forms can be provided to the subject in a therapeutically effective manner.

[0036] PDE7 proteins and inhibitors

[0037] Cyclic nucleotide phosphodiesterase type 7 (PDE7) has been identified as a distinct family based on its primary amino acid sequence and distinct enzymatic activities. The PDE genes identified as PDE7 (PDE7A and PDE7B) encode for cAMP-specific PDEs. The biochemical and pharmacological characterization of PDE7 indicates that PDE7 is a high affinity cAMP-specific PDE-isozyme that does not alter the level of cGMP. PDE7 is not inhibited by selective inhibitors of other PDE-isozymes. The PDE7 enzyme selectively hydrolyzes cAMP and is characterized as an enzyme that is not inhibited by rolipram, a selective inhibitor of PDE4, another distinct cAMP-specific PDE family. Two subtypes have been identified within the PDE7 family, PDE7A and PDE7B. PDE7A and PDE7B are encoded by two separate genes located on chromosome 8, g13-q22 and 6q23-q24, respectively. The two gene products exhibit 70% amino acid sequence identity in their C-terminal catalytic domains.

[0038] PDE7A in humans (Uniprot ID: Q13946) has three splice variants (PDE7A1, PDE7A2 and PDE7A3); these variants are produced by alternative splicing of the N-terminus or C-terminus. PDE7A1 and PDE7A2 show 97% sequence identity and vary in their N-terminal region, while PDE7A3 is a C-terminal variant of PDE7A1, but is a shorter protein that still shows 99% sequence identity with PDE7A1. The nucleotide sequence of PDE7A, transcript variant 1, is accessible in public databases. The human PDE7A1 protein has 482 amino acids. The nucleotide sequence of PDE7A, transcript variant 2, is accessible in public databases. The human PDE7A2 protein has 456 amino acids. The human PDE7A3 protein has 424 amino acids. The nucleotide sequence of PDE7A, transcript variant 3, is accessible in public databases. The PDE7A protein has a region of about 270 amino acids at the carboxyl terminus that shows significant similarity (about 23% homology) to similar regions of other cAMP hydrolyzing PDEs. This region serves as a catalytic domain. The amino terminal region of the protein is different from that of other PDEs and is likely to mediate the unique and regulatory properties that are specific to this family of enzymes. In skeletal muscle, PDE7 is the dominant PDE isozyme. The expression of variant PDE7A is much higher than that of variant PDE7B.

[0039] Three splice variants of PDE7B have been reported: PDE7B1, PDE7B2 and PDE7B3 with unique N-terminal sequences. The protein sequence of human PDE7B (Uniprot ID: Q9NP56) is accessible in public databases. Similar to the PDE7A protein, the amino-terminal region of the PDE7B protein is different, possibly explaining the unique and regulatory properties that are characteristic of a single PDE family. The PDE7B protein shows homology (~23%) with other cAMP-dependent PDEs within the catalytic domain. The PDE7B polypeptide has 59% homology with PDE7A.

[0040] Relative to other PDE families, PDE7 also has a unique location in mammalian subjects. PDE7A expression has been detected in most tissues analyzed (including skeletal muscle, heart, kidney and spleen). PDE7B expression has been detected in the following: brain, peripheral blood mononuclear cells, liver, heart, kidney, small intestine, and skeletal muscle. In skeletal muscle, PDE7A expression is much higher than the expression of variant PDE7B, and the latter shows higher expression in the brain.

[0041] In the practice of the method of the present invention, representative PDE7 inhibitors that inhibit the phosphodiesterase activity of PDE7 include: molecules that bind to PDE7 and inhibit the enzymatic activity of PDE7 (e.g., small molecule inhibitors or blocking peptides or proteins / protein fragments / fusion proteins that bind to PDE7 and reduce enzymatic activity), molecules that reduce the expression of PDE7 at the transcriptional and / or translational levels (e.g., PDE7 antisense nucleic acid molecules, PDE7-specific RNAi molecules and PDE7 ribozymes, DNA enzymes), and PDE7-directed gene therapy, thereby preventing PDE7 from cleaving cAMP. PDE7 inhibitors can be used alone as primary therapy, or as adjuvant therapy in combination with other therapies to enhance the therapeutic benefits discussed in this application.

[0042] Inhibition of PDE7 is characterized by at least one of the following changes occurring as a result of administration of a PDE7 inhibitor according to the methods of the invention: inhibition of the PDE7-dependent cleavage of the 3'-phosphodiester bond in cAMP to form 5'-adenosine monophosphate (5'-AMP), reduction in gene or protein expression levels of PDE7 as measured, for example, by gene expression analysis (e.g., RT-PCR analysis) or protein analysis (e.g., Western blot).

[0043] In some embodiments, the PDE7 inhibitor is a molecule or composition that inhibits the expression of PDE7A, PDE7B, or both PDE7A and PDE7B, such as antisense or small inhibitory nucleotides (e.g., siRNA) that specifically hybridize to cellular mRNA and / or gene DNA corresponding to the target PDE7 gene, thereby inhibiting their transcription and / or translation, or a ribozyme that specifically cleaves the target PDE7 mRNA.

[0044] Effectiveness of PDE7 Inhibitors:

[0045] In one embodiment, the PDE7 inhibitor used in the methods of the present invention is a compound that is sufficiently potent to be effective at an IC 50 <50 μM, preferably less than or about 1 μM, inhibits the enzymatic activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B). In one embodiment, the PDE7 inhibitor is potent enough to inhibit the enzymatic activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) with an IC 50 Inhibits the enzymatic activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) at about 0.1 to about 600 nM. In one embodiment, the PDE7 inhibitor is potent so that it is expressed as an IC 50 From about 0.2 to about 100 nM, preferably with IC 50 The enzyme activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) is inhibited at about 1 to about 100 nM.

[0046] Determination of IC of PDE7 (PDE7A or PDE7B) inhibitors 50 Representative methods are well known in the art, such as the scintillation proximity assay (SPA).

[0047] PDE7A or PDE7B selective inhibitors:

[0048] In one embodiment, the PDE7 inhibitor used in the methods of the invention is a PDE7A inhibitor. In one embodiment, the PDE7A inhibitor is potent so that it is expressed as an IC 50 The enzyme activity of PDE7A is inhibited at about 0.1 to about 600 nM.

[0049] In some embodiments, the PDE7 inhibitor exhibits isozyme selective activity to PDE7A. A PDE7A selective inhibitor reduces PDE7A activity by at least 2 times, more preferably at least 10 times, at least 20 times, at least 50 times, or at least 100 times, of reducing PDE7B activity. In some embodiments, a PDE7A inhibitor is an inhibitor whose selectivity for inhibiting PDE7A activity is at least 10 times (e.g., at least 20 times, or at least 50 times, or at least 100 times) of the selectivity for the enzymatic activity of any other PDE (PDE1-6, 7B, and 8-11).

[0050] In one embodiment, the PDE7B inhibitor is so potent that the IC 50 The enzyme activity of PDE7B is inhibited by about 0.1 to about 600 nM.

[0051] In some embodiments, PDE7 inhibitors exhibit isozyme selective activity to PDE7B. PDE7B selective inhibitors reduce PDE7B activity by at least 2 times, more preferably at least 10 times, at least 20 times, at least 50 times, or at least 100 times, of reducing PDE7A activity. In some embodiments, PDE7B inhibitors are inhibitors whose selectivity for inhibiting PDE7B activity is at least 10 times (e.g., at least 20 times, or at least 50 times, or at least 100 times) of the selectivity for inhibiting the enzymatic activity of any other PDE (PDE1-6, 7A, and 8-11).

[0052] Types of PDE7 inhibitors:

[0053] The PDE7 inhibitor can be any agent type, including but not limited to, chemical compounds, proteins or polypeptides, peptidomimetics, nucleic acid molecules, ribozymes, DNA enzymes, protein degraders, or gene therapy. In some embodiments, the PDE7 inhibitor is a small molecule inhibitor, including natural and synthetic substances with low molecular weight, for example, peptides, peptidomimetics and non-peptide inhibitors such as chemical compounds.

[0054] Chemical compounds:

[0055] PDE7 inhibitors useful in the methods of the present invention include agents that are administered into the bloodstream by conventional routes (eg, oral, intramuscular, subcutaneous, transdermal, buccal, intravenous, etc.) and ultimately transported through the vascular system to inhibit PDE7 in skeletal muscle and vasculature.

[0056] The following is a description of exemplary PDE7 inhibitors for use in the methods of the present invention. They can be orthosteric, allosteric or other inhibitors. If not explicitly defined later, the following terms are used:

[0057] i) Aryl: a functional group derived from an aromatic ring or a ring structure having or not having a heteroatom when one hydrogen is removed from the ring structure,

[0058] ii) Alkyl: In a broad sense, a hydrocarbon group formed when a hydrogen atom is removed from an alkane, alkene, or alkyne group,

[0059] iii) Alkoxy: a functional group comprising an alkyl group bonded to oxygen,

[0060] iv) Acyl group: a functional group having the formula RC=O, wherein R is an aryl group, an alkyl group or other structures.

[0061] The PDE7 inhibitors used in the methods of the present invention are selected from those compounds generally disclosed or specifically disclosed in U.S. Patent No. 11,685,745 and WO 2019 / 014305, each of which is expressly incorporated herein by reference in its entirety.

[0062] In one embodiment, the PDE7 inhibitor used in the methods of the present invention has the formula:

[0063]

[0064] (1), ((1) is also called spiro derivative),

[0065] or a pharmaceutically acceptable salt thereof, wherein X is -CH or -N; Y is selected from: -H, halogen, and -C 1-4 alkyl; Z are each independently selected from: -H, -halogen, and -C 1-4 Alkyl; V is selected from: bond, -(CH2) m -,-(CH2) m O(CH2) n -,-(CH2) m O(CH2) n C(O)-, -(CH2) M N[(CH2) N R 1A ]-,-(CH2) m C(O)O-, -(CH2) m C(O)-, -(CH2) m C(O)N[(CH2) n R 1A ]-,-L 1 -L 2 -, -L 1 -L 2 -L 3 -, -L 1 -L 2 -L 3 -L 4 -, and -L1 -L 5 ; m is each independently 0, 1, 2 or 3; n is each independently 0, 1, 2 or 3; L 1 is-C(O)(CH2) m -,-[C(R 1A )2] m -or-(CH2) m -;L 2 Yes -N[(CH2) n R 1A ]-or-N((CH2) n R 1A )(CH2) p -;L 3 Selected from -(CH2) m -C 3-7 Cycloalkyl, -[C((CH2) n R 1B )2] m [C((CH2) n R 1C )2] n -,-[N[(CH2) m R 1A ](CH2) n ]-,-[(CH2) m N((CH2) n R 1A )(CH2) p ]-,-[(CH2) m C(O)N((CH2) n R 1B )(CH2) p ]-,-(CH2) m C(O)-,-[C(R 1A )2] m - and - [(CH2) p O]-;L 4 Selected from -(CH2) m C(O)-, -(CH2) m O-, -C 1-6 Alkyl, -C 3-7 Cycloalkyl, heteroaryl, aryl, 3-10 membered heterocycloalkyl, and -CH(OH)-, the -C 1-6 Alkyl, -C 3-7 Cycloalkyl, heteroaryl, aryl, and 3-10 membered heterocycloalkyl are each optionally substituted with 1 to 4 R 2A ; L 5 Selected from -C(O)(CH2) m N[(CH2) n R1B ]-,-C(O)(CH2) m -, -CH(OH)- and -(CH2) m C(O)O-; p is each independently 0, 1, 2 or 3; R 1A Each is independently selected from: -H, -OH, -CN, halogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 haloalkyl, and -C 1-6 Alkoxy, the -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 Haloalkyl, and -C 1-6 Each alkoxy group is optionally substituted with 1 to 4 R 2A ; R 1B Each is independently selected from: -H, -OH, -CN, halogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 haloalkyl, and -C 1-6 Alkoxy, the -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 Haloalkyl, and -C 1-6 Each alkoxy group is optionally substituted with 1 to 4 R 2A ; R 1C Each is independently selected from: -H, -OH, -CN, halogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 haloalkyl, and -C 1-6 Alkoxy, the -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 Haloalkyl, and -C 1-6 Each alkoxy group is optionally substituted with 1 to 4 R 2A ; W is selected from: -H, -halogen, -OH, -CN, -C 1-6 Alkyl, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -SO2C1-6 Alkyl, -(CH2) m R 1A , -(CH2) m N(R 1B )2,-(CH2) m O(CH2) n R 1A , -(CH2) m S(CH2) n R 1A , -(CH2) m C(O)C 1-6 Alkyl, -(CH2) m C(O)heterocycloalkyl, -(CH2) m C(O)OH, -(CH2) m C(O)OC 1-6 Alkyl, -(CH2) m C(O)NH2, -(CH2) m C(O)N(C 1-4 alkyl)2, and -(CH2) m C(O)NH(C 1-4 alkyl), the aryl, heteroaryl, 3-15 membered heterocycloalkyl, and -C 3-7 The cycloalkyl groups are each optionally substituted with 1 to 5 R 3A ; R 2A Each independently selected from: halogen, -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -(CH2) m N(C 1-4 Alkyl)2, -OCH2(CH2) m R 2AA , -CH2(CH2) m R 2AA , -C 1-6 Alkyl-OH, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)R2AA , -NHC(O)R 2AA ,-C(O)NH(C 1-4 alkyl), -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -N(R 2AA )2, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 alkyl)2, and -CH2CF2C 3-7 Cycloalkyl, the aryl, heteroaryl, 3-15 membered heterocycloalkyl, and -C 3-7 The cycloalkyl groups are each optionally substituted with 1 to 5 substituents independently selected from the group consisting of: -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 Alkyl), -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, and -C(CH3)2OH; R 3A Each independently selected from: halogen, -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -(CH2) m N(C 1-4 Alkyl)2, -OCH2(CH2) m R 3AA , -CH2(CH2) m R 3AA , -C 1-6 Alkyl-OH, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)R 3AA , -NHC(O)R 3AA ,-C(O)NH(C 1-4 alkyl), -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -N(R 3AA )2, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 alkyl)2, and -CH2CF2C 3-7 Cycloalkyl, the aryl, heteroaryl, 3-15 membered heterocycloalkyl, and -C 3-7 The cycloalkyl groups are each optionally substituted with 1 to 5 substituents independently selected from the group consisting of: -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 Alkyl), -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, and -C(CH3)2OH; R 2AA Each independently selected from: -H, -OH, -SO2C1 -6 Alkyl, halogen, -CN, -C 1-6 Alkoxy, -C 1-6 Haloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 alkyl), -NH2, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 alkyl)2, and -C(O)aryl; R 3AA Each independently selected from: -H, -OH, -SO2C 1-6 Alkyl, halogen, -CN, -C 1-6 Alkoxy, -C 1-6 Haloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 alkyl), -NH2, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 alkyl)2, and -C(O)aryl.

[0066] In one embodiment, the PDE7 inhibitor used in the methods of the present invention has the formula:

[0067]

[0068] (1A), ((1A) is also called benzoxazole derivatives),

[0069] or a pharmaceutically acceptable salt thereof, wherein Y is selected from: -H, -F, -Cl, -Br, and -C 1-4 Alkyl; Z is selected from: -H, -F, and -C 1-4 Alkyl; V is selected from: a bond, -CH2-, -C(O)-, and -NR a -, where R a Yes -H, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, or -CH2CH2OC 1-6 Alkyl; W is selected from: -H, -halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -CH2OC 1-5 Alkyl, -CH2OH, -CH2CH2OH, -CH2CH2OCH3, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, -C(O)OC 1-4 Alkyl, -C 3-7 Cycloalkyl, the -C 3-7Cycloalkyl is optionally substituted with one or more -halogen or -C 1-6 Alkyl, -C 1-6 Aryl, -C 1-6 heteroaryl, the aryl or heteroaryl is optionally substituted, -OH, -OC 1-6 alkyl, -OCH2CH2OCH3, -OCH2C(O)N(CH3)2, -O-tetrahydropyranyl, -O-piperidinyl, optionally substituted heterocycloalkyl, and -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , and -(CH2) n -R d , where R C Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, wherein R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R b together to form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), and the 4-15 membered monocyclic, bicyclic or tricyclic ring is optionally substituted with 1 to 4 R b1 , where R b1 are each independently selected from halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridinyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridinyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole, or -C(O)phenyl.

[0070] In one embodiment, the PDE7 inhibitor used in the methods of the present invention has the formula:

[0071]

[0072] (1B), ((1B) is also called benzofuran derivatives),

[0073] or a pharmaceutically acceptable salt thereof, wherein Y is selected from: -H, -F, -Cl, -Br, and -C 1-4 Alkyl; Z is selected from: -H, -F and -CH3; V is selected from: bond, -CH2-, -C(O)-, and -NR a -, where R a Yes -H, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, and -CH2CH2OC 1-6 Alkyl; W is selected from: -H, halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -CH2OC 1-5 Alkyl, -CH2OH, -CH2CH2OH, -CH2CH2OCH3, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, -C(O)OC 1-4 Alkyl, -C 3-7 Cycloalkyl, the -C 3-7 Cycloalkyl is optionally substituted with one or more halogen or -C 1-6 Alkyl, -C 1-6 Aryl, -C 1-6 heteroaryl, the aryl or heteroaryl is optionally substituted, -OH, -OC 1-6 alkyl, -OCH2CH2OCH3, -OCH2C(O)N(CH3)2, -O-tetrahydropyranyl, -O-piperidinyl, optionally substituted heterocycloalkyl, and -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , and -(CH2) n -R d , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, wherein R d is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, -C 3-7 halocycloalkyl, oxetane, pyrrolidine, pyrrolidone, piperidine, piperidone, tetrahydropyranyl, tetrahydrofuranyl, oxepane, morpholine, 3-azabicyclo[3.1.0]hexane, tetrahydrothiophene-1,1-dioxide, tetrahydro-2H-thiopyran-1,1-dioxide, thiomorpholine-1,1-dioxide, tetrahydrothiophene 1,1-dioxide, 1,3-dihydroisobenzofuran, benzofuran, indoline, benzodioxene, benzodioxole, phenyl, benzyl, -CH2CH2phenyl, -CH2CH2CH2phenyl, furan, pyrrole, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, pyridine, pyrimidine, thiophene, pyrrolopyridine, or benzimidazole, the R d Optionally substituted with up to 4 substituents each independently selected from: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -cyclopropyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R btogether to form a monocyclic, bicyclic or tricyclic ring selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, 2-oxa-8-azaspiro[4.5]decane, 2-oxa-8- azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxazepine 5,6,7,8-Tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-Tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydropyrido[3,4-d]pyridazin-1(2H)-one pyrrolidine, spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidine-4,4'-thieno[3,2-c]pyridine], and 5',6'-dihydro-4'H-spiro[piperidine-4,7'-thieno[2,3-c]pyridine]), each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0074] In one embodiment, the PDE7 inhibitor used in the methods of the present invention has the formula:

[0075]

[0076] (1C), ((1C) is also called a methylene-substituted 7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one derivative),

[0077] or a pharmaceutically acceptable salt thereof, wherein Y is selected from: -H, -F, -Cl, -Br, and -CH3; W is -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-6 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c and -(CH2) n -R d , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, wherein R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, or -heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R b Together they form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), said 4-15 membered monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0078] In one embodiment, the PDE7 inhibitor used in the methods of the present invention has the formula:

[0079]

[0080] (1D), ((1D) is also known as an acylated 7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1′-cyclohexane]-7-one derivative),

[0081] or a pharmaceutically acceptable salt thereof, wherein Y is selected from: -H, -F, -Cl, -Br, and -CH3; W is -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c and -(CH2) n -R d , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, wherein R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, aryl, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R b Together they form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), said 4-15 membered monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0082] In one embodiment, the PDE7 inhibitor used in the methods of the present invention has the formula:

[0083]

[0084] (1E), ((1E) is also called a methylene-substituted 7,8-dihydro-6H-spiro[[1,3]furo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one derivative),

[0085] or a pharmaceutically acceptable salt thereof, wherein Y is selected from: -H, -F, -Cl, -Br, and -CH3; W is -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , and -(CH2) n -R d , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, wherein R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R b Together they form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), said 4-15 membered monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0086] In one embodiment, the PDE7 inhibitor used in the methods of the present invention has the formula:

[0087]

[0088] (1F), ((1F) is also known as an acylated 7,8-dihydro-6H-spiro[[1,3]furo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one derivative),

[0089] or a pharmaceutically acceptable salt thereof, wherein Y is selected from: -H, -F, -Cl, -Br, and -CH3; W is -C 1-6 Aryl, -C 1-6 heteroaryl, the aryl or heteroaryl is optionally substituted, or -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , and -(CH2) n -R d , where R c Yes-C2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, wherein R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R b Together they form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), said 4-15 membered monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0090] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, -2-oxa-8-azaspiro[4.5]decan-3-one, Spiro[4.5]decane, 2-oxa-8-azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxazepine 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydro pyrrolopyridine, spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidine-4,4'-thieno[3,2-c]pyridine], and 5',6'-dihydro-4'H-spiro[piperidine-4,7'-thieno[2,3-c]pyridine], each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0091] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl or -C 3-7 Cycloalkyl; the -C 3-7 Cycloalkyl is optionally substituted with one or more halogen or -C 1-6 alkyl.

[0092] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is selected from: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -CH2OC 1-5 Alkyl, -CH2OH, -CH2CH2OH, -CH2CH2OCH3, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, -C(O)OC 1-4 Alkyl, -C 3-7 Cycloalkyl, the -C 3-7 Cycloalkyl is optionally substituted with one or more halogen or -C 1-6 Alkyl, optionally substituted -C 1-6 Aryl, optionally substituted -C 1-6 Heteroaryl, -OH, -OC 1-6alkyl, -OCH2CH2OCH3, -OCH2C(O)N(CH3)2, -O-tetrahydropyranyl, -O-piperidinyl, and -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R b Together they form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), said 4-15 membered monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0093] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is selected from: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -CH2OC 1-5 Alkyl, -CH2OH, -CH2CH2OH, -CH2CH2OCH3, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, -C(O)OC1-4 Alkyl, -C 3-7 Cycloalkyl, the -C 3-7 Cycloalkyl is optionally substituted with one or more halogen or -C 1-6 Alkyl, -C 1-6 Aryl, -C 1-6 heteroaryl, the aryl or heteroaryl is optionally substituted, -OH, -OC 1-6 alkyl, -OCH2CH2OCH3, -OCH2C(O)N(CH3)2, -O-tetrahydropyranyl, -O-piperidinyl, and -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)piperidine, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, -C 3-7halocycloalkyl, oxetane, pyrrolidine, pyrrolidone, piperidine, piperidone, tetrahydropyranyl, tetrahydrofuranyl, oxepane, morpholine, 3-azabicyclo[3.1.0]hexane, tetrahydrothiophene-1,1-dioxide, tetrahydro-2H-thiopyran-1,1-dioxide, thiomorpholine-1,1-dioxide, tetrahydrothiophene-1,1-dioxide, 1,3-dihydroisobenzofuran, benzofuran, indoline, benzodioxene, benzodioxole, phenyl, benzyl, -CH2CH2phenyl, -CH2CH2CH2phenyl, furan, pyrrole, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, pyridine, pyrimidine, thiophene, pyrrolopyridine, benzimidazole, the R d Optionally substituted with up to 4 substituents each independently selected from: -F, -C 1-6 Alkyl, -C 1-6 Haloalkyl, cyclopropyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, phenyl, pyrrolidone, hydroxypiperidine, benzyl, imidazole, pyridine, wherein n is 0, 1, 2 or 3; or, two R b together to form a monocyclic, bicyclic or tricyclic ring selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, 2-oxa-8-azaspiro[4.5]decane, 2-oxa-8- azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxaza 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydropyrrolopyridine, Spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidine-4,4'-thieno[3,2-c]pyridine], and 5',6'-dihydro-4'H-spiro[piperidine-4,7'-thieno[2,3-c]pyridine], the 4-15 membered monocyclic, bicyclic or tricyclic ring optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0094] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is -N(R b )2, where R b Each independently selected from: -H, -C 1-6Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)piperidine, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, -C 3-7 halocycloalkyl, oxetane, pyrrolidine, pyrrolidone, piperidine, piperidone, tetrahydropyranyl, tetrahydrofuranyl, oxepane, morpholine, 3-azabicyclo[3.1.0]hexane, tetrahydrothiophene-1,1-dioxide, tetrahydro-2H-thiopyran-1,1-dioxide, thiomorpholine-1,1-dioxide, tetrahydrothiophene-1,1-dioxide, 1,3-dihydroisobenzofuran, benzofuran, indoline, benzodioxene, benzodioxole, phenyl, benzyl, -CH2CH2phenyl, -CH2CH2CH2phenyl, furan, pyrrole, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, pyridine, pyrimidine, thiophene, pyrrolopyridine, benzimidazole, the R d Optionally substituted with up to 4 substituents each independently selected from: -F, -C 1-6Alkyl, -C 1-6 Haloalkyl, cyclopropyl, -OH, -OC 1-6 Alkyl, -OC 1-6 Haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, or -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, phenyl, pyrrolidone, hydroxypiperidine, benzyl, imidazole, pyridine, wherein n is 0, 1, 2 or 3.

[0095] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is -N(R b )2, where two R b together to form a monocyclic, bicyclic or tricyclic ring selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, -2-oxa-8-azaspiro[4.5]decane, 2-oxa-8 -azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxaza 5,6,7,8-Tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-Tetrahydroimidazo[1,2-c]pyrazine, 5,6,7,8-Tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydropyrrolopyrazine pyridine, spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidin-4,4'-thieno]3,2-c[pyridine], and 5',6'-dihydro-4'H-spiro[piperidin-4,7'-thieno]2,3-c[pyridine], the monocyclic, bicyclic or tricyclic ring optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7Cycloalkyl, -bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0096] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is selected from: -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, and -CH2CH2OCH3.

[0097] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein V is a bond, W is a halogen, -C 1-3 Alkyl, -C 1-3 Haloalkyl or -C 3-5 Cycloalkyl, the -C 3-5 Cycloalkyl is optionally substituted with one or more halogen or -C 1-3 alkyl.

[0098] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein V is -CH2- and W is: -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, or heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R bTogether they form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), said 4-15 membered monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0099] In a more specific embodiment, the PDE7 inhibitor or a pharmaceutically acceptable salt thereof for use in the method of the present invention, wherein W is selected from: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -CH2OC 1-5 Alkyl, -CH2OH, -CH2CH2OH, -CH2CH2OCH3, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, -C(O)OC 1-4 Alkyl, -C 3-7 Cycloalkyl, the -C 3-7 Cycloalkyl is optionally substituted with one or more halogen or -C 1-6 Alkyl, optionally substituted -C 1-6 Aryl, optionally substituted -C1-6 Heteroaryl, -OH, -OC 1-6 alkyl, -OCH2CH2OCH3, -OCH2C(O)N(CH3)2, -O-tetrahydropyranyl, -O-piperidinyl, and -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)piperidine, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, -C 3-7halocycloalkyl, oxetane, pyrrolidine, pyrrolidone, piperidine, piperidone, tetrahydropyranyl, tetrahydrofuranyl, oxepane, morpholine, 3-azabicyclo[3.1.0]hexane, tetrahydrothiophene-1,1-dioxide, tetrahydro-2H-thiopyran-1,1-dioxide, thiomorpholine-1,1-dioxide, tetrahydrothiophene-1,1-dioxide, 1,3-dihydroisobenzofuran, benzofuran, indoline, benzodioxene, benzodioxole, phenyl, benzyl, -CH2CH2phenyl, -CH2CH2CH2phenyl, furan, pyrrole, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, pyridine, pyrimidine, thiophene, pyrrolopyridine, benzimidazole, the R d Optionally substituted with up to 4 substituents each independently selected from: -F, -C 1-6 Alkyl, -C 1-6 Haloalkyl, cyclopropyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, phenyl, pyrrolidone, hydroxypiperidine, phenyl, benzyl, imidazole, pyridine, wherein n is 0, 1, 2 or 3; or, two R b together to form a monocyclic, bicyclic or tricyclic ring selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, 2-oxa-8-azaspiro[4.5]decane, 2-oxa-8- azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxaza 5,6,7,8-Tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydropyrrolo[1,2-a]pyrazine pyridine, spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidine-4,4'-thieno[3,2-c]pyridine], 5',6'-dihydro-4'H-spiro[piperidine-4,7'-thieno[2,3-c]pyridine], the monocyclic, bicyclic or tricyclic ring optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridinyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridinyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole and -C(O)phenyl.

[0100] In another more specific embodiment, the PDE7 inhibitor or a pharmaceutically acceptable salt thereof for use in the methods of the present invention wherein W is -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)piperidine, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, -C 3-7 halocycloalkyl, oxetane, pyrrolidine, pyrrolidone, piperidine, piperidone, tetrahydropyranyl, tetrahydrofuranyl, oxepane, morpholine, 3-azabicyclo[3.1.0]hexane, tetrahydrothiophene-1,1-dioxide, tetrahydro-2H-thiopyran-1,1-dioxide, thiomorpholine-1,1-dioxide, tetrahydrothiophene-1,1-dioxide, 1,3-dihydroisobenzofuran, benzofuran, indoline, benzodioxene, benzodioxole, phenyl, benzyl, -CH2CH2phenyl, -CH2CH2CH2phenyl, furan, pyrrole, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, pyridine, pyrimidine, thiophene, pyrrolopyridine, benzimidazole, the R d Optionally substituted with up to 4 substituents each independently selected from: -F, -C 1-6 Alkyl, -C1-6 Haloalkyl, cyclopropyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, pyrrolidone, hydroxypiperidine, phenyl, benzyl, imidazole, or pyridine, wherein n is 0, 1, 2 or 3.

[0101] In another more specific embodiment, the PDE7 inhibitor or a pharmaceutically acceptable salt thereof for use in the methods of the present invention wherein W is -N(R b )2, where two R b together to form a monocyclic, bicyclic or tricyclic ring selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, 2-oxa-8-azaspiro[4.5]decane, 2-oxa-8- azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxaza 5,6,7,8-Tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-Tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-Tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydropyrrolopyrazine pyridine, spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidine-4,4'-thieno[3,2-c]pyridine], and 5',6'-dihydro-4'H-spiro[piperidine-4,7'-thieno[2,3-c]pyridine], the monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridinyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridinyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole, or -C(O)phenyl.

[0102] In one embodiment, the PDE7 inhibitor used in the method of the present invention has the formula (1) or a pharmaceutically acceptable salt thereof, wherein W is selected from: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -CH2OC 1-5 Alkyl, -CH2OH, -CH2CH2OH, -CH2CH2OCH3, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, -C(O)OC 1-4 Alkyl, -C 3-7 Cycloalkyl, the -C 3-7 Cycloalkyl is optionally substituted with one or more halogen or -C 1-6 Alkyl, optionally substituted -C 1-6 Aryl, optionally substituted -C 1-6 Heteroaryl, -OH, -OC 1-6 alkyl, -OCH2CH2OCH3, -OCH2C(O)N(CH3)2, -O-tetrahydropyranyl, -O-piperidinyl, and -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)heterocycloalkyl, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d Yes-C 3-7 Cycloalkyl, -C 3-7 halocycloalkyl, heterocycloalkyl, aryl, and heteroaryl, each of which is optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, phenyl, or benzyl, wherein n is 0, 1, 2 or 3; or, two R b Together they form a 4-15 membered monocyclic, bicyclic or tricyclic ring, which optionally contains up to 3 additional heteroatoms each independently selected from O (oxygen), N (nitrogen) and S (sulfur), said 4-15 membered monocyclic, bicyclic or tricyclic ring being optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridinyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridinyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole, or -C(O)phenyl.

[0103] In a more specific embodiment, the PDE7 inhibitor or a pharmaceutically acceptable salt thereof for use in the method of the present invention, wherein W is selected from: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -CH2OC 1-5 Alkyl, -CH2OH, -CH2CH2OH, -CH2CH2OCH3, -C(O)C 1-6 Alkyl, -C(O)C 3-7 Cycloalkyl, -C(O)OC 1-4 Alkyl, -C 3-7 Cycloalkyl, the -C 3-7 Cycloalkyl is optionally substituted with one or more halogen or -C 1-6 Alkyl, optionally substituted -C 1-6 Aryl, optionally substituted -C 1-6 Heteroaryl, -OH, -OC 1-6 alkyl, -OCH2CH2OCH3, -OCH2C(O)N(CH3)2, -O-tetrahydropyranyl, -O-piperidinyl, and -N(R b)2 where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)piperidine, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane), -C 3-7 halocycloalkyl, oxetane, pyrrolidine, pyrrolidone, piperidine, piperidone, tetrahydropyranyl, tetrahydrofuranyl, oxepane, morpholine, 3-azabicyclo[3.1.0]hexane, tetrahydrothiophene-1,1-dioxide, tetrahydro-2H-thiopyran-1,1-dioxide, thiomorpholine-1,1-dioxide, tetrahydrothiophene-1,1-dioxide, 1,3-dihydroisobenzofuran, benzofuran, indoline, benzodioxene, benzodioxole, phenyl, benzyl, -CH2CH2phenyl, -CH2CH2CH2phenyl, furan, pyrrole, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, pyridine, pyrimidine, thiophene, pyrrolopyridine, benzimidazole, the Rd Optionally substituted with up to 4 substituents each independently selected from: -F, -C 1-6 Alkyl, -C 1-6 Haloalkyl, cyclopropyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, pyrrolidone, hydroxypiperidine, phenyl, benzyl, imidazole, or pyridine, wherein n is 0, 1, 2 or 3; or, two R b together to form a monocyclic, bicyclic or tricyclic ring selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, 2-oxa-8-azaspiro[4.5]decane, 2-oxa-8- azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxaza 5,6,7,8-Tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydropyrrolo[1,2-a]pyrazine pyridine, spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidine-4,4'-thieno[3,2-c]pyridine], 5',6'-dihydro-4'H-spiro[piperidine-4,7'-thieno[2,3-c]pyridine], the monocyclic, bicyclic or tricyclic ring optionally substituted with up to 4 substituents each independently selected from the following: halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6 Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridinyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridinyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole and -C(O)phenyl.

[0104] In another more specific embodiment, the PDE7 inhibitor or a pharmaceutically acceptable salt thereof for use in the methods of the present invention wherein W is -N(R b )2, where R b Each independently selected from: -H, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C 1-6 Haloalkyl, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, -CH2-alkenyl, -CH2-alkynyl, -CH2C 3-7 Cycloalkyl, -CH2C(O)C(CH3)3, -CH2C(O)C 1-6 Alkyl, -CH2C(O)piperidine, -CH2C(O)OC 1-6 Alkyl, -CH2C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 Alkyl)2,-CH2CF2C 3-7 Cycloalkyl, -CH2CH2-R c , where R c Yes-C 2-6 Alkynyl, -C3-7 Cycloalkyl, -OH, -OC 1-6 Alkyl, -OC(CH3)2, -OC 1-6 haloalkyl, -Ophenyl, -Opyridyl, -CH2N(CH3)2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NHCH3, -N(CH3)2, -NHC(O)CH3, or -SO2CH3, and -(CH2) n -R d , where R d is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, -C 3-7 halocycloalkyl, oxetane, pyrrolidine, pyrrolidone, piperidine, piperidone, tetrahydropyranyl, tetrahydrofuranyl, oxepane, morpholine, 3-azabicyclo[3.1.0]hexane, tetrahydrothiophene-1,1-dioxide, tetrahydro-2H-thiopyran-1,1-dioxide, thiomorpholine-1,1-dioxide, tetrahydrothiophene-1,1-dioxide, 1,3-dihydroisobenzofuran, benzofuran, indoline, benzodioxene, benzodioxole, phenyl, benzyl, -CH2CH2phenyl, -CH2CH2CH2phenyl, furan, pyrrole, pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole, pyridine, pyrimidine, thiophene, pyrrolopyridine, benzimidazole, the R d Optionally substituted with up to 4 substituents each independently selected from: -F, -C 1-6 Alkyl, -C 1-6 Haloalkyl, cyclopropyl, -OH, -OC 1-6 Alkyl, -OC 1-6 haloalkyl, -O-phenyl, -O-pyridyl, -CH2OH, -CH2OCH3, -CH2OCH2CH3, -CN, -N(CH3)2, -N(CH3)benzyl, heteroaryl, heterocycloalkyl, morpholine, pyrrolidone, hydroxypiperidine, phenyl, benzyl, imidazole, or pyridine, wherein n is 0, 1, 2 or 3.

[0105] In another more specific embodiment, the PDE7 inhibitor or a pharmaceutically acceptable salt thereof for use in the methods of the present invention wherein W is -N(R b )2, where two R btogether to form a monocyclic, bicyclic or tricyclic ring selected from the group consisting of azetidine, pyrrole, pyrrolidine, pyrrolidone, piperazine, piperazinone, piperidine, piperidone, azepane, morpholine, 1-oxa-8-azaspiro[4.5]decan-3-one, 2-oxa-5-azabicyclo[2.2.1]heptane, 2-oxa-7-azaspiro[3.5]nonane, 2-oxa-8-azaspiro[4.5]decane, 2-oxa-8- azaspiro[4.5]decan-1-one, 6-oxa-9-azaspiro[4.5]decane, 7-oxa-2-azaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, oxazabicyclo[2.2.1]heptane, thiomorpholine-1,1-dioxide, diazaheptane, 2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxaza 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine, 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine, 5,6,7,8-tetrahydropyrido[3,4-d]pyridazin-1(2H)-one, azaspiro[2.5]octane, azabicyclo[3.1.0]hexane, azabicyclo[4.1.0]heptane, diazaspiro[5.5]undecane, tetrahydroimidazopyrazine, dihydropyrrolopyridine, Spiro[chroman-2,3'-pyrrolidine]-4-one, spiro[isochroman-1,4'-piperidine], 6',7'-dihydro-5'H-spiro[piperidine-4,4'-thieno[3,2-c]pyridine], and 5',6'-dihydro-4'H-spiro[piperidine-4,7'-thieno[2,3-c]pyridine], the 4-15 membered monocyclic, bicyclic or tricyclic ring optionally substituted with up to 4 substituents each independently selected from the group consisting of halogen, -C 1-6 Alkyl, -C 1-6 Haloalkyl, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 3-7 Cycloalkyl, bicyclo[2.2.1]heptane, -C 1-6 Alkyl-OH, -C(CH3)2OH, -CH2OC 1-6 Alkyl, -CH2C(O)OCH2CH3, -CH2CH2OC 1-6 Alkyl, -CH2CH2OC 1-6 Haloalkyl, -CH2CH2C(O)OCH3, -OH, -OC 1-6 Alkyl, -OCH2-C 3-7 Cycloalkyl, -OCH2CH2OCH3, ═O, -CH2N(CH3)2, -CH2CH2N(CH3)2, -C(O)C 1-6 Alkyl, -C(O)H, -C(O)OH, -C(O)OC 1-6Alkyl, -C(O)CH3, -C(O)NH2, -C(O)NHCH3, -C(O)N(CH3)2, -CN, -NH2, -NHC(O)CH3, -N(CH3)2, -SO2CH3, oxetane, pyrrolidine, morpholine, furan, thiazole, pyridyl, phenyl, thiophene, -CH2imidazole, -CH2furan, -CH2-thiophene, -CH2pyridyl, benzyl, -C(O)-tetrahydrofuran, -C(O)pyrrole or -C(O)phenyl.

[0106] In one embodiment, the PDE7 inhibitor used in the methods of the present invention is selected from:

[0107] 5-Chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid methyl ester; 5-Chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid; 5-Chloro-2-(chloromethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[ ethyl 2-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl}acetate; 5-chloro-2-(4-methoxypiperidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-fluoro-2-[(3-methoxyazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; ,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid methyl ester; 5-chloro-4',4'-difluoro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2,4',4'-trimethyl-7,8-dihydro-6H- Spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-ethyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-propyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-(propan-2-yl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-cyclopropyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(methoxymethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(hydroxymethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(2-methoxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one )-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(2-hydroxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; N-[5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl]acetamide; 2-[bis(2-methoxyethyl)amino]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-7-oxo-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(dimethylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(morpholin-4-ylmethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(methylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(cyclopropylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(cyclopropylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(piperazin-1-ylmethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-(pyrrolidin-1-ylmethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(propan-2-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(ethylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline -9,1'-cyclohexane]-7-one; 5-chloro-2-[(4,4-difluoropiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-hydroxyethyl)(methyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3,3-difluorohexadiazole)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f ]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{2-oxa-8-azaspiro[4.5]dec-8-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(oxetan-3-yl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylacetamide;tert-Butyl 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}amino)methyl]piperidine-1-carboxylate; 5-chloro-2-({[(3,5-difluoropyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(piperidin-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-oxo-2-( 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}amino)-N-ethyl-N-methylacetamide; 5-chloro-2-[(4-methyl-3-oxopiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethyl-3-oxopiperazin-1-yl)methyl]-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(pyridin-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(pyrimidin-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(5-methoxypyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline 1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}piperidine-4-carboxylic acid ethyl ester; 5-chloro-2-({1-oxo-2-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;2-[(4-acetylpiperidin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}piperidine-4-carboxylic acid methyl ester; 5-chloro-2-({[(5-fluoropyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(2-methylpropoxy)azetidine-1 -yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(cyclopropylmethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one [1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(propan-2-yloxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-fluoroazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-methoxyazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9, 1'-cyclohexane]-7-one; 5-chloro-2-{[3-(methoxymethyl)azetidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{7-oxa-2-azaspiro[3.5]nonan-2-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methoxy-4-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({3-oxo-1-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)-N,N-dimethylacetamide; 5-Chloro-2-({[(6-methylpyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[methyl( 5-Chloro-2-({[(3-fluorooxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(3-fluorooxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(oxetane-4-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-methyloxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one [[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxetan-3-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-oxopiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({[(2-methoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(2,4-dimethoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(propan-2-yl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3,3,4-triazol-2-yl)piperazin-1-yl]methyl] 5-Chloro-2-{[(2-(hydroxymethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(2-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(2-methylpropyl)morpholin-4-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-cyclobutyl-2,2-difluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4 -f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-ethylmorpholin-4-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-cyclohexyl-2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{6-oxa-9-azaspiro[4.5]dec-9-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(1-(oxan-2-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(oxan-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3-methyl-2-oxobutyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(4,4-difluorocyclohexyl)amino]methyl}-7 ,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1r,4r)-4-methoxycyclohexyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1r,4r)-4-methoxycyclohexyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; -2-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane-5-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-ylmethyl] 5-Chloro-2-[(4-methoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(4-methoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one oxazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(3R)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3S)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3R)-3-ethoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3R)-3-(2-hydroxypropane- 5-Chloro-2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[2-(dimethylamino)ethyl](methyl)amino}methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 3-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5 ,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)-N,N-dimethylpropanamide; 5-chloro-2-({methyl[2-(morpholin-4-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-methoxypyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5, 4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)acetate; 2-[(8aR)-octahydropyrrolo[1,2-a]piperazin-2-ylmethyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(oxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one;1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}piperidine-3-carboxylic acid methyl ester; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}amino)acetate; 5-chloro-2-{[(3S)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxan-3-yl)amino]methyl}-7, 8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3S)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; (3R)-1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}piperidine-3-carboxylic acid methyl ester; 5-chloro-2-({[2-(trifluoromethoxy)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1 '-cyclohexane]-7-one; 5-chloro-2-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-diethylacetamide; (2S)-2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylpropanamide;(2R)-2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylpropanamide; 5-chloro-2-({[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[({3-oxabicyclo[ 3.1.0]hexan-6-yl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxepan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxolan-3-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3,3-difluoro-2-hydroxypropyl)amino]methyl}-7,8-dihydro-6 H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(4-cyclopropyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,6-dimethyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3-methyloxolan-3-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one;5-Chloro-2-{[4-(2-methoxyethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazin-2-ylmethyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; (3R)-1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}pyrrolidine-3-carboxylic acid methyl ester; 5-chloro-2-{[4-(2,2-difluoroethyl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-methyloxolan-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7 -one; 5-chloro-2-({[(3R)-oxolan-3-ylmethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3-fluorooxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,2-difluoro-3-hydroxypropyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one ; 5-chloro-2-{[(2,2-difluorocyclopentyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[4-(methoxymethyl)oxan-4-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxan-3-ylmethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-4',4'-difluoro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-4',4'-difluoro-2-({[(3S)-oxacyclopentane-3-ylmethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(1,3-oxazol-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9, 1'-cyclohexane]-7-one; 5-chloro-2-{[(1,3-oxazol-5-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(1,2-oxazol-3-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(1,3-oxazol-4-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(1,2-oxazol-3-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one [(1-methyl-1H-pyrazol-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(1,2-oxazol-5-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethoxy}-N,N-dimethylacetamide; 5-chloro-2-[(oxan-4-yloxy)methyl]-7,8- dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(1-methylpiperidin-4-yl)oxy]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-[2-(dimethylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-(morpholine-4-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-N,N-dimethyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-(4-methylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-N-(2-methoxyethyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl]-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2-methoxyethyl)-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-N-methyl-N-(oxacyclohexane-4-ylmethyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(3R)-3-ethoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5, 4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylacetamide; 3-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylpropanamide; 5-chloro-2-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylpropanamide 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl-N-methylformamido}acetate; 5-chloro-N-methyl-N-[2-(methylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-2-[4-(dimethylamino)piperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(2-methoxyethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aR)-octahydropyrrolo[1,2- a]piperazine-2-carbonyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-methyl-N-(oxan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-(3-methoxypyrrolidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3R)-3-methoxypiperidine-1-carbonyl]-7,8-dihydro-6H -spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(oxan-3-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(3S)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3R)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline oxazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3S)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-7-oxo-N-[2-(trifluoromethoxy)ethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(3R)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-(4-ethylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(propan-2-yl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(2,2-difluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl 5-Chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(piperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-7-oxo-N-[(3R)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-[4-(2-fluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[ 5-Chloro-N-(2,2-difluorocyclopentyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-[4-(methoxymethyl)oxan-4-yl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-(3-fluorooxan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide Hexane]-2-carboxamide; 5-chloro-N-(2,2-difluoro-3-hydroxypropyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-7-oxo-N-[(3S)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-7-oxo-N-[(3S)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-7-oxo-N-[(3R)-oxolan-3-yl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-4',4'-difluoro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4,4-difluoropiperidin-1-yl)methyl]-5-fluoro-7,8-dihydro-6H-spiro[[1 ,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-fluoro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)-N,N-dimethylacetamide; 2-({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)-N,N-dimethylacetamide [[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylacetamide; 5-chloro-4',4'-difluoro-2-({[(3S)-oxacyclohexan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3R)-oxacyclohexan-3-ylmethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3S)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof; or;

[0108] A compound selected from the group consisting of:

[0109] 5-Chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-[2-(dimethylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-(morpholine-4-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide 5-Chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-(4-methylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(4-methoxypiperidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(4-methoxypiperidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2-methoxyethyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2-methoxyethyl)-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide 1-(4-(5-chloro-2-((3R)-3-ethoxypyrrolidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one); 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylacetamide;3-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylpropanamide; 5-chloro-2-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl-N-methylformamido}acetate; 5-chloro-N-methyl-N- [2-(Methylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[4-(dimethylamino)piperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]- ]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(2-methoxyethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aR)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-methyl-N-(oxan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1 ,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-(3-methoxypyrrolidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3R)-3-methoxypiperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(oxan-3-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-2-[(3S)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3R)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3S)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-7-oxo- N-[2-(trifluoromethoxy)ethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(3R)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(4-ethylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(propan-2-yl)piperazine-1-carbonyl]-7,8-dihydro-6 H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(2,2-difluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(piperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one oxazolin-9,1'-cyclohexane]-7-one; 5-chloro-7-oxo-N-[(3R)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[4-(2-fluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2,2-difluorocyclopentyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-N-[4-(methoxymethyl)oxan-4-yl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-(3-fluorooxan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-[4-(methoxymethyl)oxan-4-yl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide -N-(2,2-difluoro-3-hydroxypropyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-7-oxo-N-[(3S)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-7-oxo-N-[(3S)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-7-oxo-N-[(3R)-oxolan-3-yl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-4',4'-difluoro-7-oxo-N-[(3R)-oxolan-3-yl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide -7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid methyl ester; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-4',4'-difluoro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof; or;

[0110] A compound selected from the group consisting of:

[0111] 5-Chloro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(chloromethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(methoxymethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(hydroxymethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-propyl-7,8-dihydro -6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-ethyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(dimethylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(morpholin-4-yl)methyl]-7 ,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-hydroxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(methylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(cyclopropylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; [(Piperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(pyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(2-methoxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(2-hydroxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(propan-2-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(ethylamino)methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f ]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4,4-difluoropiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-hydroxyethyl)(methyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3,3-difluoroazepine cyclobutane-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3,3-difluoropyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-propionylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline oxazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({2-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(oxetan-3-yl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylacetamide;tert-Butyl 2-{[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl}methyl)amino]methyl}piperidine-1-carboxylate; 5-chloro-2-({[(3,5-difluoropyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(piperidin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-oxo-2- 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N-ethyl-N-methylacetamide; 5-chloro-2-[(4-methyl-3-oxopiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethyl-3-oxopiperazin-1-yl)methyl]-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(pyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(pyrimidin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(5-methoxypyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-4-carboxylic acid ethyl ester; 5-chloro-2-({1-oxo-2-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;2-[(4-acetylpiperidin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-4-carboxylate; 5-chloro-2-({[(5-fluoropyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(2-methylpropoxy)azetidine- 1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(cyclopropylmethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(cyclopropylmethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; [1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(propan-2-yloxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-fluoroazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-methoxyazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1 '-cyclohexane]-7-one; 5-chloro-2-{[3-(methoxymethyl)azetidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({7-oxa-2-azaspiro[3.5]nonan-2-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methoxy-4-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({3-oxo-1-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)(methyl)amino]-N,N-dimethylacetamide; 5-Chloro-2-({[(6-methylpyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane] -7-one; 5-chloro-2-({methyl[(oxetane-4-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({methyl[(3-methyloxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-fluorooxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane ]-7-one; 5-chloro-2-({[(oxacyclohexane-4-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({2-oxa-7-azaspiro[3.5]nonan-7-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-methyloxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-2-({2-oxa-5-azabicyclo[2.2.1]heptane-5-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(oxetan-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-[(4-oxopiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(2-methoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(2,4-dimethoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(propan-2-yl)piperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[1-(hydroxymethyl)cyclopentyl]amino}methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(2-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(2-methylpropyl)morpholin-4-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f ]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-cyclobutyl-2,2-difluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-ethylmorpholin-4-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-cyclohexyl-2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({6-oxa-9-azaspiro[4.5]dec-9-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[1-(oxacyclohexan-2-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(oxacyclohexan-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(oxacyclohexan-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; ethyl 2-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}acetate; 2-[(4,4-difluoropiperidin-1-yl)methyl]-5-fluoro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-fluoro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9, 1'-cyclohexane]-7-one; 5-chloro-2-{[(3-methyl-2-oxobutyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-fluoro-2-[(3-methoxyazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(4,4-difluorocyclohexyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1R,4R 5-Chloro-2-{[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-[(3-methoxy-3-methylazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(4-methoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 5-Chloro-2-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[3-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3R)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one ,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3S)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-ethoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-ethoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(dimethylamino)ethyl](methyl)amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 3-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)(methyl)amino]-N,N-dimethylpropanamide;5-Chloro-2-({methyl[2-(morpholin-4-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 5-Chloro-2-[(3-methoxypyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(5-Chloro-7-oxo-7,8-dihydro- 2-{[(8aR)-octahydropyrrolo[1,2-a]pyrazin-2-yl]methyl}-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(oxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-3-carboxylic acid methyl ester; 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]acetic acid methyl ester; 5-chloro-2-{[(3S)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxan-3-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl -cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3S)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;(3R)-1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-3-carboxylic acid methyl ester; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methoxy)-N,N-dimethylacetamide; 5-chloro-2-[(oxan-4-yloxy)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(trifluoromethoxy)ethyl]amino}methyl 5-Chloro-2-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{[5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{[3-(dimethylamino)pyrrolidin-1-yl]methyl} ... (2S)-2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylpropanamide; (2R)-2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylpropanamide; 5-chloro-2-({[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5, 5-Chloro-2-{[(oxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(oxacycloheptan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(oxacycloheptan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(3,3-difluoro-2-hydroxypropyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(4-cyclopropyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2,6-dimethyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxacyclopentane-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxacyclopentane-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3-methyloxacyclopentane-3-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one [1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(2-methoxyethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{[(8aS)-octahydropyrrolo[1,2-a]pyrazin-2-yl]methyl}-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f] Quinazoline-9,1'-cyclohexane]-7-one; (3R)-1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)pyrrolidine-3-carboxylic acid methyl ester; 5-chloro-2-{[4-(2,2-difluoroethyl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-methyloxolan-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({[(3R)-oxacyclohexan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[({[(3R)-oxacyclohexan-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3-fluorooxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-2-{[(2,2-difluoro-3-hydroxypropyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,2-difluorocyclopentyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[4-(methoxymethyl)oxan-4-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-2-[({[(3S)-oxolan-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1,3-oxazol-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro- -2-{[(1-methylpiperidin-4-yl)oxy]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-[({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl}methyl)(methyl)amino]-N,N-dimethylacetamide; 2-[({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylacetamide;5-Chloro-4',4'-difluoro-2-{[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-4',4'-difluoro-2-[({[(3S)-oxacyclopentane-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2,4',4'-trimethyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-4',4'-difluoro-2-({[(3S)-oxacyclohexane-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-[({[(3R)-oxacyclohexane-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3S)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1,3-oxazol-5-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1 '-cyclohexane]-7-one; 5-chloro-2-({[2-(1,2-oxazol-3-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1,3-oxazol-4-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1-methyl-1H-pyrazol-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-chloro-2-({[(1,2-oxazol-5-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof; or;

[0112] 5'-Chloro-7'-(hydroxymethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-[4-(2-fluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; N-{2-[benzyl(methyl)amino]ethyl}-5'-chloro-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-{[4-(propan-2-yl)piperazin-1-yl]methyl}-7',8' -dihydro-6'H-spiro[cyclohexane-1,9'-furo[23-f]quinazoline]-7'-one; 5'-chloro-2'-{[methyl({[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]methyl})amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; 5'-chloro-2'-(4-methylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(4-ethylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one [2,3-f]quinazoline]-7'-one; 5'-chloro-N-(2-methoxyethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(2-methoxyethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-(piperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-(azetidine-1-carbonyl)-5'- Chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-(pyrrolidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-(morpholine-4- 5'-Chloro-2'-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-[4-(2,2-difluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-(piperidin-1-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-(morpholin-4-ylmethyl)-7',8 '-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(pyrrolidin-1-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[(4-methylpiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-ethyl-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; Chloro-7'-oxo-N-[2-(propan-2-yloxy)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(4-methoxypiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(4-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-methoxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[ Cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-methyl-N-(2-methylpropyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-cyclopentyl-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(1-hydroxy-3-methylbutan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-N-(1-methylpiperidin-4-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(2-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-[4-(2-hydroxyethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-(3-hydroxypropyl)-7'-oxo-7 ',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(4-hydroxybutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-hydroxyethyl)-7'-oxo-N-propyl-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[2-(pyrrolidin-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9' -furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethylamino)ethyl]-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[3-(1H-imidazol-1-yl)propyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethylamino)ethyl]-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; ]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-hydroxybutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[3-(dimethylamino)propyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 2'-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-N-methyl-7'-oxo-N-[2-(pyridin-2-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2-cyanoethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2-ethoxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-7'-oxo-N-(oxolane- 2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-methoxyethyl)-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[2-(thien-2-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-cyclopentyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-ethyl-N-(2-hydroxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(3-hydroxypiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-[2-(1H-pyrrol-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide Formamide; 5'-chloro-N-methyl-N-(1-methylpyrrolidin-3-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-formamide; 5'-chloro-N-(3-hydroxy-3-phenylpropyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-formamide; 5'-chloro-2'-[3-(hydroxymethyl)-3-(2-methylpropyl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-N-[(2,3-dimethoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-7'-[2-(trifluoromethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-7-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[3-(morpholin-4-yl)propyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one formamide; 5'-chloro-N-[(2-methoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[3-(1H-imidazol-1-ylmethyl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2-[4-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperazin-1-yl]acetate; 5'-chloro-N-[( 2,4-dimethoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-methoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2,2-dimethyloxan-4-yl)-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; -[(1-methyl-1H-1,3-benzodiazol-2-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3,5-dimethoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-{5H,6H,7H,8H-imidazo[1,2-a]pyrazine-7-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-[2-(pyridin-2-yl)pyrrolidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-(2-hydroxy-2-phenylethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[2-(2,3-dihydro-1H-indol-1-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-[(2,3-dimethoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-N-[(5-methyl-1H-1,3-benzodiazol-2-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-[3-(trimethyl-1H-pyrazol-4-yl)propyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline] -2'-carboxamide; 5'-chloro-2'-{octahydropyrrolo[1,2-a]piperazine-2-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(5-cyclopropyl-1H-pyrazol-3-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- Quinazoline]-2'-carboxamide; 5'-chloro-N-[(2,4-dimethoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-(1-benzylpyrrolidin-3-yl)-5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(2,3-difluoro-4-methoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-N-{[4-(dimethylamino)phenyl]methyl}-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(1-methyl-1H-imidazol-2-yl)methyl]-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-[4-(pyridin-4-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; N-[(5-tert-butyl 2'-(4-Benzylpiperazine-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1-methylpiperidin-4-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-(3-methoxypiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide Hydrogen-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-methyl-7'-oxo-N-[(trimethyl-1H-pyrazol-4-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(pyridin-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)propyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H -spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(4-methyl-2-phenylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[3-(dimethylamino)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(morpholin-4-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-7'-oxo-N-[2-(pyridin-3-yloxy)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(2-fluoro-4-methoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)azetidine-3-carbonitrile; 5'-Chloro-2'- {3-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-7-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-[2-(2-oxopyrrolidin-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-(2,2,6,6-tetramethyloxan-4-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- 2'-carboxamide; 2'-[(1R,5S)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(4-fluorophenoxy)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[2-(1H-pyrazol-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2 '-carboxamide; 5'-chloro-N-[4-(4-hydroxypiperidin-1-yl)phenyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(3,3-dimethyl-2-oxobutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(furan-2-ylmethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-2'-{4-[2-(dimethylamino)ethyl]piperidine-1-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-[4-(5-chloropyridin-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[(2-methoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2-hydroxy 5'-Chloro-N-[(4-cyanophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-[3-oxo-4-(propan-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-{[5-(difluoromethoxy)pyridin-2-yl]methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide}-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(oxetane-3-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1R,5S)-6,6-difluorobicyclo[3.1.0]hexane-3-yl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-[2-(2H-1,3-benzo[1-piperazine-1-carbonyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one 5'-Chloro-N-[(4-ethyl-4H-1,2,4-triazol-3-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(4-ethyl-4H-1,2,4-triazol-3-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(4-cyano-3-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide;2-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-ylcarboxamido}-N,N-diethylacetamide; 5'-chloro-7'-({6'-methyl-5',6'-dihydro-4'H-spiro[piperidin-4,7'-thieno[2,3-c]pyridine]-1-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(6-methylpyridin-3-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline ]-7'-carboxamide; 5'-chloro-7'-oxo-N-[(trimethyl-1H-imidazol-2-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(5-methylpyridin-3-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-[(5-phenyl-1,2-oxazol-3-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide amide; 2'-{6-azaspiro[2.5]octane-6-carbonyl}-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(oxan-4-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-({6',7'-dihydro-5'H-spiro[piperidin-4,4'-thieno[3,2-c]pyridine]-1-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7 '-one; 5'-chloro-N-(1-methoxy-2-methylpropane-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[1-(pyridin-3-yl)piperidin-4-yl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-({3,4-dihydrospiro[2-benzopyran-1,4'-piperidin]-1'-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-7'-oxo-N-(2-phenoxyethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 3-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylcarboxamido}-N,N-dimethylpropanamide; 5'-chloro-N-[1-(methoxymethyl)cyclopropyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7'-oxo- 7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(cyclobutylmethyl)-7'-oxo-N-(oxolan-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-7'-[4-(furan-2-ylmethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-7'-oxo-7',8'-dihydro-6 'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[1-(pyridin-2-yl)cyclopropyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(4-methyloxan-4-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-{[1-(ethoxymethyl)cyclopropyl]methyl}-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[ 2'-(4-{bicyclo[2.2.1]heptane-2-yl}piperazine-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1-methyl-1H-imidazol-5-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-7'-oxo-N-[2-oxo-2-(piperidin-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-(3-hydroxyazetidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-oxo-N-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-(3-hydroxyazetidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one -N-[1-(oxacyclohexane-4-yl)cyclopropyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(prop-2-yn-1-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N,N-diethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(1-methyl-2-oxo- 5'-Chloro-2'-[(1R,5S,6S)-6-(pyridin-2-yl)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[(6-fluoropyridin-2-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-ethyl-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-{6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-{7,7-difluoro-3-azabicyclo[4.1.0]heptane-3-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-{6,6-difluoro-3-azabicyclo[3.1.0]hexane-3-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-(2,2,2-trifluoroethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[(5-oxopyrrolidin-2-yl)methyl]-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide amide; 5'-chloro-N-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(4,4-difluorocyclohexyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-{bicyclo[1.1.1]pentan-1-yl}-5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'- Chloro-N-[(1S,3R)-3-fluorocyclopentyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-methyl-7'-oxo-N-(prop-2-en-1-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-7'-oxo-N-(prop-2-yn-1-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-7'-{2-ethyl-1-oxo- 1H,2H,5H,6H,7H,8H-pyrido[3,4-d]pyridazine-6-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; 5'-chloro-N-(1,3-dihydro-2-benzofuran-5-ylmethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[4-(methoxymethyl)oxan-4-yl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-N-cyclobutyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-{9-propionyl-2,9-diazaspiro[5.5]undecane-2-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-methyl-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- 2'-carboxamide; 5'-chloro-2'-[(1R,5S,6S)-6-(2-methoxyphenyl)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; N-butyl-5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-{8-ethoxy-2H,3H,4H,5H-pyrido[3,2-f][1,4]oxazepine; -4-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-[2-(thien-3-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-cyclobutyl-2,2-difluoroethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-propyl-7',8'-dihydro-6'H-spiro[cyclohexane- 1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; (2R)-1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)pyrrolidine-2-carboxylic acid; 5'-chloro-7'-[(1R,6R)-7,7-difluoro-6-methyl-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-methyl-7'-oxo-N-{[4-(propan-2-yl)-4H-1,2,4-triazole- 3-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-({4-oxo-3,4-dihydrospiro[1-benzopyran-2,3'-pyrrolidine]-1'-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-cyclopropyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-ethyl-7'-oxo-N-propyl-7',8'-dihydro-6' H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-propyl-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(thien-3-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperidine-4-carbonitrile;5'-Chloro-2'-[3-(dimethylamino)pyrrolidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; N-benzyl-5'-chloro-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(thien-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-methoxyphenyl)methyl ]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(3-hydroxypyrrolidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N,N-bis(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(furan-2-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H -spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-[2-(hydroxymethyl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-[4-(propan-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-[2-(furan-2-yl)pyrrolidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one [2,3-f]quinazoline]-7'-one; 5'-chloro-N-(3-methylbutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-cyanoethyl)-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(pyridin-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-7'-oxo-N-[3-(pyrrolidin-1-yl)propyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-7'-oxo-N-(pentan-3-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 2'-(azepane-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[2-(1H-imidazol-1-yl)ethyl]-7'-oxo- 7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-methyl-7'-oxo-N-(pyridin-3-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-N-(1-methylpiperidin-4-yl)-7'-oxo-7',8'-dihydro-6' H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-ethyl-1,2-oxazol-5-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(3-methylbutan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-(3-methylpiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide furano[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-7'-(2,2-dimethylmorpholine-4-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(3-hydroxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide;5'-Chloro-7'-[4-(dimethylamino)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-oxo-N-[3-(2-oxopyrrolidin-1-yl)propyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-(4-methylpiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-oxo-N-(thiophen-3-ylmethyl)- 7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-benzyl-5'-chloro-N-(2-hydroxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-N-methyl-7'-oxo-7',8'- dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(4-cyclohexylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(4-hydroxy-4-phenylpiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[4-(oxolane-2-carbonyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2, 3-f]quinazolin]-7'-one; 5'-chloro-2'-{4-[(dimethylamino)methyl]piperidine-1-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-yl}carbonyl)-N-methylpiperidine-4-carboxamide; 5'-chloro-N-[2-(4-methoxyphenyl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-carboxamide;5'-Chloro-N-[2-(dimethyl-1,2-oxazol-4-yl)ethyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-2'-[4-(1,3-thiazol-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-{[4-(1H-imidazol-1-yl)phenyl]methyl}-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3 -f]quinazoline]-2'-carboxamide; 2'-(4-tert-butylpiperazine-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(3-methoxyphenyl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(pyrrolidin-1-yl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro- -N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(morpholin-4-yl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[4-(3-methoxyphenyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo- 5'-Chloro-N-(1-hydroxy-3-phenylpropan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(1-hydroxy-3-phenylpropan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(1-hydroxy-3-phenylpropan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2H-1,3-benzodioxol-5-ylmethyl)-5'-chloro-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;3-[1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperidin-2-yl]propanoic acid methyl ester; 5'-chloro-7'-(4-cyclopentylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperidin-2-yl]propanoic acid methyl ester furano[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-[4-(2-methylpropionyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; N-benzyl-5'-chloro-N-(3-hydroxypropyl)-7'-oxo-7',8 '-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(2-methoxyethyl)-7'-oxo-N-(thien-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethylamino)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-{5H,6H,7H-pyrrolo[3,4-b]pyridine-6-carbonyl}-7',8'-dihydro-6'H-spiro [Cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-cyclohexyl-N-(2-hydroxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethyl-1,3-thiazol-2-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-({[(3R,4R)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1, 9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[2-(2-hydroxyethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-[(3-oxopiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({[(1-methyl-1H-pyrazol-3-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-{[(2-methoxyethyl)(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperidine-4-carbonitrile; 5'-chloro-2'-{[(2-hydroxyethyl)(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(pyridine-4 -yl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[(oxan-4-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-[(8aS)-octahydropyrrolo[1,2-a]piperazin-2-ylmethyl]- 5'-Chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[(oxolan-2-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 3-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}(ethyl)amino)propionitrile; 5'-chloro-2'-{[(pyridin-2-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane- 1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[(2-methylsulfonylethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 2'-{[benzyl(2-hydroxyethyl)amino]methyl}-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-{[(furan-2-ylmethyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-[(4-methoxypiperidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 2'-[(4-acetyl-1,4-diazaheptan-1-yl)methyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-{[4-(2-hydroxyethyl)piperazin-1-yl ]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({4-[(dimethylamino)methyl]piperidin-1-yl}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-{[4-(oxolane-2-carbonyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({[(5-oxopyrrolidin-2-yl)methyl](propan-2-yl)amino}methyl)-7 ',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7 '-one; 5'-chloro-2'-({[3-(2-oxopyrrolidin-1-yl)propyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline] [2,3-f]quinazolin]-2'-ylmethyl}-N-methylpiperidine-4-carboxamide; 5'-chloro-2'-{[(3-hydroxypropyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}piperidine-3-carboxamide;3-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}(methyl)amino)-N-methylpropanamide; 5'-chloro-2'-[{(1R,5S,6S)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[ethyl(2-hydroxyethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one Quinazoline]-7'-one; 5'-chloro-2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[(3-hydroxypiperidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[ (2R,6S)-2,6-dimethylmorpholin-4-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(4-ethyl-4H-1,2,4-triazol-3-yl)methyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-{2-oxa-6-azaspiro[3.5]nonan-6-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one ketone; 5'-chloro-7'-{[ethyl(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(5-cyclopropyl-1H-pyrazol-3-yl)methyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[3-(dimethylamino)propyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2-(4-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperazin-1-yl)pyridine-3-carbonitrile; 5'-Chloro-2'-{[3-(1H-imidazol-1-ylmethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one ketone; 5'-chloro-2'-{[4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(2-methoxyethyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[methyl(pyridin-3-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 4-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}-thiomorpholine-1,1-dione; 5'-chloro-2'-{[(4-hydroxy-2-methylbutan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 4-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperazine-1-carboxaldehyde; 5'-chloro-2'-{[4-( [({[4-(morpholin-4-yl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 4-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}-N,N-dimethylpiperazine-1-carboxamide; 5'-chloro-2'-[({[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]methyl}amino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-{[3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}azetidine-3-carbonitrile; 4-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}}amino)-sulfurized cyclopentane-1,1-dione; 5'-chloro-2'-[(4-methylsulfonylpiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 7-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-2-carboxylic acid ethyl ester; 2'-{6-azaspiro[2.5]octan-6-ylmethyl}-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'- furano[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[(2,2,2-trifluoroethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{octahydropyrrolo[1,2-a]piperazin-2-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[4-(furan-2-ylmethyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one quinazolin]-7'-one; 5'-chloro-2'-{[methyl(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 3-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}amino)-tetrahydrothiophene-1,1-dione; 5'-chloro-2'-{[4-(pyridin-3-ylmethyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-[(4-methyl-1,4-diazepan-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[4-(dimethylamino)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-({methyl[(trimethyl-1H-pyrazol-4-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7' -one; 5'-chloro-7'-{[3-oxo-4-(propan-2-yl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-{[(2,2-dimethyloxan-4-yl)(ethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(pyrrolidine-1-carbonyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3 -f]quinazolin]-7'-one; 5'-chloro-2'-{[(1,3-oxazol-5-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-[(propylamino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({[(1-methyl-1H-pyrazol-5-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one ketone; 5'-chloro-2'-{[4-(oxetan-3-yl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({methyl[2-(pyridin-2-yl)ethyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[(2-methoxyethyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-{5H,6H,7H-pyrrolo[3,4-b]pyridin-6-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-({[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-({[2-(dimethylamino)ethyl](ethyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one 5'-Chloro-2'-[(3-hydroxypyrrolidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-[({[6-(morpholin-4-yl)pyridin-3-yl]methyl}amino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[methyl(propyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline] -7'-one; 5'-chloro-2'-({[3-(3,5-dimethyl-1H-pyrazol-1-yl)propyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-[(2,2-dimethylmorpholin-4-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[(4-ethylpiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- 7'-one; 5'-chloro-2'-({[(3-ethyl-1,2-oxazol-5-yl)methyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[methyl(pyridin-2-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}piperidine-4-carboxamide;5'-Chloro-2'-({[2-(2-oxopyrrolidin-1-yl)ethyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-[({[1-(ethoxymethyl)cyclopropyl]methyl}amino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-({[2-(dimethyl-1,2-oxazol-4-yl)ethyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; N-( 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperidin-4-yl)acetamide; 5'-chloro-2'-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[methyl(1-methylpiperidin-4-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({6,6-dimethyl-3-azabicyclo[3.1.0] 5'-Chloro-2'-({[(1-methyl-1H-imidazol-2-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[3-(hydroxymethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[(2-hydroxyethyl)(propyl)amino]methyl}-7',8'-dihydro-6' H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 2-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}(methyl)amino)ethyl acetate; 2'-[(3-aminopyrrolidin-1-yl)methyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; N-{2-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}amino)ethyl}acetamide;5'-Chloro-2'-{[4-(hydroxymethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-{[(piperidin-3-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-{[(pyrrolidin-3-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-benzoyl-5'-chloro-7',8'-dihydro-6 'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(pyridine-4-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-acetyl-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(3S,4R)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one ; 5'-chloro-2'-{[(3-fluorooxan-4-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(3R)-oxolan-3-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(3S)-oxolan-3-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 7'-({[(3R,4S)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-({[(3S,4R)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-{[(2-methoxyethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-chloro-2'-{[(oxetane-3-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; and pharmaceutically acceptable salts thereof. ;

[0113] In one embodiment, the pharmaceutical composition comprises a compound of formula (1) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0114] In one embodiment, a method of treating, inhibiting or alleviating a condition or improving symptoms of a condition comprising having an abnormal or dysregulated signaling pathway mediated by PDE7 in a subject, the method comprising administering a compound of formula (1) or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0115] In one embodiment, the PDE7 inhibitor compound used in the method of the present invention has formula (1) or is selected from the following compounds:

[0116] 5-Chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3-methoxy-3-methylazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[3-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro -6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(dimethylamino)ethyl](methyl)amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(oxacyclohexane-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof.

[0117] In one embodiment, the PDE7 inhibitor compound used in the methods of the present invention has the formula:

[0118]

[0119]

[0120] More specific embodiments include pharmaceutical compositions comprising a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

[0121] The preparation of the above compounds is described in U.S. Patent No. 11,685,745 and WO 2019 / 014305.

[0122] The present invention provides a method for treating a disease associated with chronic fatigue (DACF) by administering to a patient in need thereof an amount of a PDE7 inhibitor effective to inhibit the enzymatic activity of PDE7, wherein such inhibition of PDE7 enzymatic activity is the primary therapeutic mode of action of the PDE7 inhibitor in treating DACF.

[0123] For each PDE7 inhibitory chemical compound used in the method of the present invention, all possible stereoisomers and geometric isomers are included. Compounds include not only racemic compounds, but also optically active isomers. When the PDE7 inhibitor is desired as a single enantiomer, it can be obtained by resolving the final product or by stereospecific synthesis from isomerically pure starting materials or using chiral auxiliary reagents, for example, see Ma, Z., et al., Tetrahedron: Asymmetry 8 (6): 883-888, 1997. The resolution of the final product, intermediate, or starting material can be completed by any suitable method known in the art. In addition, in the case where the tautomer of the compound can be used, the present invention is intended to include all tautomeric forms of the compound.

[0124] The PDE7 inhibitors comprising an acidic part can form a pharmaceutically acceptable salt with a suitable cation. Suitable pharmaceutically acceptable cations include alkali metals (e.g., sodium or potassium) and alkaline earth metals (e.g., calcium or magnesium) cations. The pharmaceutically acceptable salts of PDE7 inhibitors (which include a basic center) are acid addition salts formed with pharmaceutically acceptable acids. Examples include hydrochlorides, hydrobromides, sulfates or bisulfates, phosphates or hydrogen phosphates, acetates, benzoates, succinates, fumarates, maleates, lactates, citrates, tartrates, gluconates, methanethiocyanates (methanefulgonate), benzenesulfonates and p-toluenesulfonates. In view of the foregoing, any reference to compounds that can be used for the methods of the present invention that appear in this application is intended to include PDE7 inhibitors, and pharmaceutically acceptable salts and solvates thereof.

[0125] The compounds of the present invention can be administered therapeutically as pure chemical substances, but it is preferred that the PDE7 inhibitor is administered as a pharmaceutical composition or formulation, for example as a tablet or capsule. Therefore, the present invention further provides a pharmaceutical composition or formulation comprising: a PDE7 inhibitor or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable carriers, and optionally other therapeutic ingredients and / or preventive ingredients. Suitable carriers are compatible with the other ingredients of the formulation and are harmless to the recipient. The compounds of the present invention can also be carried in a delivery system to provide sustained release of the compound or to enhance the absorption or activity of the compound, such as a liposome or hydrogel system for injection, a microparticle, nanoparticle or micellar system for oral or parenteral delivery, or a graded capsule system for oral delivery.

[0126] Example

[0127] The following examples describe the use of some compounds according to the present invention. These examples are not limiting and are merely illustrative of the present invention.

[0128] Example 1 - PDE7 Enzymatic Assay and IC 50 Determination

[0129] The ability of compounds to inhibit PDE7 can be measured using the following assay protocol: IC for PDE7 and variants 50 The assay method for the assay includes human recombinant insect Sf9 cells as the enzyme source. The substrate is 0.1 μM FAM-cAMP and the vehicle is 1.0% DMSO or 1.0% PEG 400. The preincubation time and temperature are 15 minutes at 25°C and the incubation time and temperature are 30 minutes at 25°C. The incubation buffer consists of the following: 10 mM Tris-HCl, pH 7.2, 10 mM MgCl2, 0.05% NaN3, and 0.1% phosphate-free BSA. The quantitative method used is the fluorescence spectroscopic quantification of fluorescein-AMP-IMAP. The IBMX reference standard is run as an integral part of each assay to ensure the validity of the results obtained. IC 50 IC is the concentration of the compound (inhibitor) tested in the assay at which the compound (inhibitor) can reduce the enzymatic activity of PDE7 by 50%. 50 The values ​​were finally analyzed by nonlinear least squares regression using MathIQ TM (ID Business Solutions Ltd., UK).

[0130] Compounds to be tested as PDE7 inhibitors were initially dissolved in vehicle at a concentration of 30 mM. These solutions were tested as the highest test concentrations and then further diluted in a cascade fashion at a ratio of 1:6 to obtain solutions with the desired lower test concentrations. Each assay was performed in duplicate.

[0131] As an illustrative and non-limiting example, the following compounds according to the invention have the IC 50 The inhibitory effects of PDE7 show their advantages as therapeutically effective substances:

[0132]

[0133] Example 2 - Na + / K + In vitro model of ATPase activation with more residual muscle force (less fatigue)

[0134] Model Introduction

[0135] The patent claims that PDE7 inhibitors can improve the physical dysfunction and symptoms of ME / CFS, such as disorders associated with chronic fatigue (DACF). Muscle fatigue and weakness (e.g., loss of grip strength) are hallmarks of ME / CFS patients. The primary target of PDE7 inhibition is skeletal muscle, whose energetic function is severely disturbed in ME / CFS and is presumed to be important in the symptomatology of ME / CFS. + / K + Insufficient ATPase stimulation plays a key role in the development of a disorder in which sodium levels rise in the muscle, ultimately leading to calcium overload. The latter can lead to a profound functional energy disorder or impairment. Isolated rat muscles (either soleus or extensor digitorum longus) are a good candidate for studying Na + / K + A well-characterized and validated model of the function of ATPase. The isolated rat soleus muscle is particularly suitable for in vitro experiments because it is very thin, so that a blood supply is not required. It has been demonstrated under different experimental conditions that cAMP stimulates Na via protein kinase A (PKA). + / K + ATPase to reduce the decrease in contractile force that occurs after measures such as the administration of carbachol or high KCl concentrations (12.5 mM) or worsening of the energy situation during electrical stimulation. In the experimental setup used, the high KCl concentration buffer caused a partial depolarization, leading to a disturbance of sodium influx and a decrease in excitability, and subsequently a decrease in muscle force. Stimulation of Na + / K + ATPase reduces intracellular sodium levels to physiological levels to restore excitability and muscle strength during electrical stimulation. Preventing and reducing the loss of muscle strength during this process indicates that the test compound with the described mode of action of PDE7 inhibition can effectively stimulate Na + / K + ATPase.

[0136] The decrease in strength in the soleus muscle can be considered as muscle fatigue and is associated with the loss of grip muscle strength in ME / CFS patients. Since phosphodiesterase isoform 7 (PDE7) is the main PDE isozyme that elevates cAMP in skeletal muscle, this in vitro model is suitable for testing the effects of PDE7 inhibitors, in particular their effects on force production disturbed by mechanisms that worsen excitability or energetic conditions. Since the isozyme variant PDE7A shows much higher expression in skeletal muscle than the variant PDE7B, it is expected that PDE7 inhibitors have a higher inhibitory activity against PDE7A compared to PDE7B. High KCl (12.5 mM) in the buffer was used to induce a decrease in contractile force. Electrical stimulation after the addition of high KCl buffer showed a decrease in contractile force to values ​​close to 13% of the initial force, which is considered as muscle fatigue. Na stimulated by cAMP + / K + High levels of ATPase activity can counteract the reduction in excitability and loss of strength. Drugs such as salbutamol can maintain contractile force and muscle fatigue compared to control conditions. Since PDE7 is the dominant phosphodiesterase isozyme in skeletal muscle, PDE7 inhibition is expected to strongly enhance the effects of salbutamol by inhibiting the decline in cAMP, the production of which is stimulated by salbutamol through adenylate cyclase. Experiments using PDE7 inhibitors are carried out in the presence of the β2-adrenergic agonist salbutamol to produce a level of cAMP, the decline of which is then inhibited by the PDE7 inhibitor so that its level is still significantly elevated.

[0137] method

[0138] Muscle preparation and culture: 5-week-old female Sprague Dawley rats were used. After isoflurane anesthesia and cervical dislocation, the intact soleus muscle of the animals was dissected. The soleus muscle was vertically mounted between two field stimulation electrodes (thick copper wire) at rest length in an organ bath containing 15 mL of culture medium. The lower end of the muscle was fixed to a clamp fixed to the bottom of the organ bath, and the upper end of the muscle was fixed to an isometric force sensor (force sensor K300 HugoSachs) through a clamp that allows the measurement of isometric contractions, and a tension of 100 mN was applied.

[0139] Force Measurement: The experimental setup for force measurement allows data from 6 muscles to be recorded in parallel simultaneously in separate culture chambers. Force values ​​were recorded and stored using the Notocord HEM data acquisition system. The standard culture medium was Krebs-Ringer (KR) bicarbonate buffer (pH 7.4), which contained (in mM): 120.1 NaCl, 25.1 NaHCO3, 4.7 KCl, 1.2 KH2PO4, 1.2 MgSO4, 1.3 CaCl2, and 5 glucose. The culture was carried out at 30°C. The buffer was continuously aerated with a mixture of 95% O2 and 5% CO2. Before stimulation, the muscles were equilibrated in standard culture medium with a mixture of 95% oxygen and 5% carbon dioxide for 30 minutes (min).

[0140] Electrical stimulation protocol: After a 30-min equilibration period, the muscles were field stimulated using a Hugo Sachs stimulator (HSE) at 83 Hz, 2-3 ms pulses, 12 V (biphasic), 0.2-0.5 s training width to deliver optimal force values. After optimizing the stimulation protocol, the muscles were stimulated every 10 minutes for 30 minutes in the above buffer to obtain control force values, and then the contractile force was weakened by the depolarizing effect of 12.5 mM KCl in the buffer.

[0141] Study of test compounds: At time 0 (T0), the above buffer was exchanged with a buffer containing KCl 12.5mM. Then stimulation was performed every 5min for a total of 30min. In the control group, the high KCl buffer caused a strong loss of force. 10 minutes before the initial buffer was replaced with a new buffer of 12.5mM high KCl (10 minutes before T0), the test compound was added to the organ bath containing 15mL of buffer solution in a volume of 0.1mL, and after the replacement, the test compound was newly added to the new high KCl buffer again. Two control groups were included. One group had only high KCl 12.5mM buffer and one group had high KCl 12.5mM + salbutamol 1μM. PDE7 inhibitors were always tested in the presence of salbutamol 1μM.

[0142] evaluate

[0143] The depolarization of high KCl 12.5mM causes a strong loss of power in the control group. Effective drugs will show a lower loss of contractile force, thus maintaining contractile force. The residual contractile force after 30min in high KCl buffer is selected as a potency parameter and is related to the final value of the force stimulated in the initial buffer in the same organ bath. The percentage of the residual force values ​​between the different groups is compared and used for statistical calculations. PDE7 inhibitor drugs are tested in the presence of salbutamol 1 μM, and this effect is compared with those effects of the salbutamol 1 μM control group.

[0144] result

[0145] As an illustrative and non-limiting example, the following compounds according to the invention were tested according to the above protocol and delayed the decrease in soleus muscle force values ​​in rats, as shown below, thus demonstrating their advantage as therapeutically active substances:

[0146]

[0147] Compared to baseline force values ​​under normal potassium concentration, soleus muscle force values ​​under depolarization with high extracellular potassium concentration (12.5 mM) decreased significantly to 13.6 ± 1.9% (mean ± SEM, n = 30) mean residual contractile force.

[0148] Results for control and compounds are shown in the table above as mean values ​​with standard error of the mean (SEM). The loss of contractile force was moderately reduced by stimulation with salbutamol (1 μM). Salbutamol 10 μM alone left an average of 33.6% (SEM: 7.3) residual contractile force at n=9, an effect only slightly stronger than salbutamol 1 μM.

[0149] PDE7 inhibitors were studied in the presence of salbutamol 1 μM to produce cAMP, the concentration of cAMP can then be enhanced as follows: inhibiting its hydrolysis by PDE7 inhibition. Therefore, PDE7 inhibitors were evaluated for the effects of salbutamol 1 μM and tested for statistical significance. PDE inhibition by the pan-PDE inhibitor dipyridamole (high concentration) plus a moderate dose of salbutamol (1 μM) showed an even stronger numerical effect than salbutamol alone at a high dose of 10 μM, as did potent PDE7 inhibitors. Specific PDE7 inhibitors with formula No. 1G (2266633-30-9) and formula No. 1M (2266637-12-9) were more active than dipyridamole.

[0150] in conclusion:

[0151] PDE7 inhibitors, especially PDE7A inhibitors, reduce muscle fatigue as shown by the preservation of contractile force under conditions of reduced excitability caused by sodium overload caused by the depolarization of high KCl buffer. The mechanism is through Na + / K + Based on these actions, PDE7 inhibitors can treat muscle fatigue and weakness.

[0152] In addition, due to the discovery of stimulation of Na + / K +ATPases reduce intracellular sodium (high intramuscular sodium causes calcium overload through the reverse mode of the sodium calcium exchanger (NCX), causing muscle damage and mitochondrial dysfunction), so PDE7 inhibitors can treat and prevent the harmful secondary consequences of mitochondrial dysfunction and energy depletion. This depletion would otherwise lead to physiological stimulation of vasoactive mediators from skeletal muscle, which usually physiologically means increased muscle blood flow. These mediators are then overproduced due to the very poor energy situation and are therefore released into the systemic blood flow (osmosis). Therefore, these mediators with pain, hyperalgesia, spasm-inducing and microvascular leakage-inducing properties can reach every organ to cause a variety of symptoms of diseases associated with chronic fatigue. These symptoms include pain, edema and spasm, which are prevented by treatment involving PDE7 inhibition in the form of indirect effects.

Claims

1. A substance having phosphodiesterase-7 inhibitory activity (PDE7 inhibitor), for use as an active ingredient in a therapeutic agent having phosphodiesterase-7 inhibitory activity for the treatment and prevention of chronic fatigue, exhaustion and / or exertion intolerance, and for the treatment and prevention of diseases associated with chronic fatigue, exhaustion and / or exertion intolerance.

2. The substance according to claim 1, wherein the disease associated with chronic fatigue, exhaustion and / or exertion intolerance is a disease diagnosed as: myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS), systemic exertion intolerance, exertion intolerance, long-term COVID condition, post-Covid-19 syndrome (PCS), post-acute Covid syndrome (PACS), post-acute sequelae of SARS-CoV-2 infection (PASC), post-vaccination syndrome (post-vac-syndrome) after COVID-19 vaccination (Long Vax) and vaccination against other bacteria, viruses and pathogenic agents, and post-infectious fatigue after viral, bacterial, or fungal infections, in particular ME / CFS of non-infectious, non-inflammatory and non-immune causes.

3. The agent of claim 1, wherein chronic fatigue and exhaustion is a symptom of or is associated with cancer (cancer-related fatigue), fibromyalgia, Ehlers-Danlos syndrome, Marfan syndrome, Gulf War illness, the autoimmune diseases rheumatoid arthritis, ANCA vasculitis and Sjögren's syndrome, and other autoimmune diseases with fatigue and exhaustion as debilitating symptoms.

4. The substance according to any one of claims 1 to 3, wherein the PDE7 inhibitory substance is in the form of IC 50 <50μM, preferably IC 50 ≤1μM, more preferably IC 50 0.1 to 600 nM, particularly preferably IC 50 The range is about 0.2 to about 100 nM, and more preferably, the range is about 0.2 to about 100 nM. 50 A substance that inhibits the enzymatic activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) at about 1 to about 100 nM.

5. The substance according to any one of claims 1 to 4, wherein the PDE7 inhibitory substance is a substance that inhibits the enzymatic activity of PDE7A, preferably, the PDE7 inhibitory substance is in the form of IC 50 <50μM, preferably IC 50 ≤1μM, more preferably IC 50 0.1 to 600 nM, particularly preferably IC 50 The range is about 0.2 to about 100 nM, and more preferably, the range is about 0.2 to about 100 nM. 50 A substance that inhibits the enzymatic activity of PDE7A at about 1 to about 100 nM.

6. The substance according to any one of claims 1, 2, 3, 4 and 5, wherein the PDE7 inhibitor stimulates Na+ in skeletal muscle by increasing cAMP. + / K + -ATPase and NCLX and improve blood flow to skeletal muscle and brain and inhibit neuroinflammation.

7. The substance according to any one of claims 1 to 6, wherein the PDE7 inhibitor or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier are present in a pharmaceutical preparation, preferably in the form of oral medication, intravenous, subcutaneous, intramuscular, pharyngeal and nasal administration.

8. The substance according to any one of claims 1 to 7, wherein the PDE7 inhibitor is selected from the formula (1): or a pharmaceutically acceptable salt thereof, wherein X is -CH or -N; Y is selected from: -H, halogen, and -C 1-4 alkyl; Z are each independently selected from: -H, -halogen, and -C 1-4 Alkyl; V is selected from: bond, -(CH2) m -,-(CH2) m O(CH2) n -,-(CH2) m O(CH2) n C(O)-, -(CH2) M N[(CH2) N R 1A ]-,-(CH2) m C(O)O-, -(CH2) m C(O)-, -(CH2) m C(O)N[(CH2) n R 1A ]-,-L 1 -L 2 -, -L 1 -L 2 -L 3 -, -L 1 -L 2 -L 3 -L 4 -, and -L 1 -L 5 ; m is each independently 0, 1, 2 or 3; n is each independently 0, 1, 2 or 3; L 1 Yes -C(O)(CH2) m -,-[C(R 1A )2] m -or-(CH2) m -;L 2 Yes -N[(CH2) n R 1A ]- or -N((CH2) n R 1A )(CH2) p -;L 3 Selected from -(CH2) m -C 3-7 Cycloalkyl, -[C((CH2) n R 1B )2] m [C((CH2) n R 1C )2] n -,-[N[(CH2) m R 1A ](CH2) n ]-,-[(CH2) m N((CH2) n R 1A )(CH2) p ]-,-[(CH2) m C(O)N((CH2) n R 1B )(CH2) p ]-,-(CH2) m C(O)-,-[C(R 1A )2] m - and - [(CH2) p O]-;L 4 Selected from -(CH2) m C(O)-, -(CH2) m O-, -C 1-6 Alkyl, -C 3-7 Cycloalkyl, heteroaryl, aryl, 3-10 membered heterocycloalkyl, and -CH(OH)-, the -C 1-6 Alkyl, -C 3-7 Cycloalkyl, heteroaryl, aryl, and 3-10 membered heterocycloalkyl are each optionally substituted with 1 to 4 R 2A ; L 5 Selected from -C(O)(CH2) m N[(CH2) n R 1B ]-,-C(O)(CH2) m -, -CH(OH)- and -(CH2) m C(O)O-; p is 0, 1, 2 or 3; R 1A Each is independently selected from: -H, -OH, -CN, halogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 haloalkyl, and -C 1-6 Alkoxy, the -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 Haloalkyl, and -C 1-6 Each alkoxy group is optionally substituted with 1 to 4 R 2A ; R 1B Each is independently selected from: -H, -OH, -CN, halogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 haloalkyl, and -C 1-6 Alkoxy, the -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 Haloalkyl, and -C 1-6 Each alkoxy group is optionally substituted with 1 to 4 R 2A ; R 1C Each is independently selected from: -H, -OH, -CN, halogen, -C 1-6 Alkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 haloalkyl, and -C 1-6 Alkoxy, the -C 3-7 Cycloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 1-6 Haloalkyl, and -C 1-6 Each alkoxy group is optionally substituted with 1 to 4 R 2A ; W is selected from: -H, -halogen, -OH, -CN, -C 1-6 Alkyl, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -SO2C 1-6 Alkyl, -(CH2) m R 1A , -(CH2) m N(R 1B )2,-(CH2) m O(CH2) n R 1A , -(CH2) m S(CH2) n R 1A , -(CH2) m C(O)C 1-6 Alkyl, -(CH2) m C(O)heterocycloalkyl, -(CH2) m C(O)OH, -(CH2) m C(O)OC 1-6 Alkyl, -(CH2) m C(O)NH2, -(CH2) m C(O)N(C 1-4 alkyl)2, and -(CH2) m C(O)NH(C 1-4 alkyl), the aryl, heteroaryl, 3-15 membered heterocycloalkyl, and -C 3-7 The cycloalkyl groups are each optionally substituted with 1 to 5 R 3A ; R 2A Each independently selected from: halogen, -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -(CH2) m N(C 1-4 Alkyl)2, -OCH2(CH2) m R 2AA , -CH2(CH2) m R 2AA , -C 1-6 Alkyl-OH, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)R 2AA , -NHC(O)R 2AA ,-C(O)NH(C 1-4 alkyl), -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -N(R 2AA )2, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 alkyl)2, and -CH2CF2C 3-7 Cycloalkyl, the aryl, heteroaryl, 3-15 membered heterocycloalkyl, and -C 3-7 The cycloalkyl groups are each optionally substituted with 1 to 5 substituents independently selected from the group consisting of: -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 Alkyl), -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, and -C(CH3)2OH; R 3A Each independently selected from: halogen, -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -(CH2) m N(C 1-4 Alkyl)2, -OCH2(CH2) m R 3AA , -CH2(CH2) m R 3AA , -C 1-6 Alkyl-OH, -C 1-6 HaloalkylOH, -C 1-6 Halogenated alkyl-C 3-7 Cycloalkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)R 3AA , -NHC(O)R 3AA ,-C(O)NH(C 1-4 alkyl), -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, -C(CH3)2OH, -N(R 3AA )2, -C(CH3)2CH2OCH3, -CH(CH3)C(O)N(C 1-4 alkyl)2, and -CH2CF2C 3-7 Cycloalkyl, the aryl, heteroaryl, 3-15 membered heterocycloalkyl, and -C 3-7 The cycloalkyl groups are each optionally substituted with 1 to 5 substituents each independently selected from the group consisting of: -CN, ═O, -OH, -SO2C 1-6 Alkyl, -C 1-6 Alkyl, -C 1-6 Alkoxy, -C 1-6 haloalkyl, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 3-7 Cycloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 Alkyl), -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C(O)C(CH3)3, -OC 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)aryl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 Alkyl)2, -CH2CH(OH)C 3-7 Cycloalkyl, and -C(CH3)2OH; R 2AA Each independently selected from: -H, -OH, -SO2C 1-6 Alkyl, halogen, -CN, -C 1-6 Alkoxy, -C 1-6 Haloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 alkyl), -NH2, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 alkyl)2, and -C(O)aryl; R 3AA Each independently selected from: -H, -OH, -SO2C 1-6 Alkyl, halogen, -CN, -C 1-6 Alkoxy, -C 1-6 Haloalkyl, -N(C 1-4 Alkyl)2,-NH(C 1-4 alkyl), -NH2, aryl, heteroaryl, 3-15 membered heterocycloalkyl, -C 2-6 Alkenyl, -C 2-6 Alkynyl, -C 3-7 Cycloalkyl, -C(O)C 1-6 Alkyl, -C(O)heterocycloalkyl, -C(O)OC 1-6 Alkyl, -C(O)N(C 1-4 alkyl)2, and -C(O)aryl.

9. The substance according to any one of claims 1 to 8, wherein the PDE7 inhibitor is selected from the following substances: spirocyclic derivatives; benzoxazole derivatives; benzofuran derivatives; methylene substituted 7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one derivatives; acylated 7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one derivatives; methylene substituted 7,8-dihydro-6H-spiro[[1,3]furo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one derivatives; and acylated 7,8-dihydro-6H-spiro[[1,3]furo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one derivatives.

10. The substance according to any one of claims 1 to 9, wherein the PDE7 inhibitor is a compound selected from the group consisting of 5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid methyl ester; 5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid; 5-chloro-2-(chloromethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro -6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(2-methoxyethoxy)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}ethyl acetate; 5-chloro-2-(4-methoxypiperidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-fluoro-2-[(3- 5-Chloro-4',4'-difluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid methyl ester; 5-Chloro-4',4'-difluoro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-4',4'-difluoro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one [5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2,4',4'-trimethyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-ethyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-propyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(propan-2-yl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-cyclopropyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(methoxymethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(hydroxymethyl)-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(2-methoxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(2-hydroxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; N-[5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl]acetamide; 2-[bis(2-methoxyethyl)amino]-5-chloro -7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(dimethylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(morpholine-4 -ylmethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-hydroxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(methylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(cyclopropylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-(piperazin-1-ylmethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(pyrrolidin-1-ylmethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(propan-2-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(ethylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9, 1'-cyclohexane]-7-one; 5-chloro-2-{[(2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4,4-difluoropiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-hydroxyethyl)(methyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 5-Chloro-2-[(3,3-difluoropyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3,3-difluoropyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4 -f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-propionylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{2-oxa-8-azaspiro[4.5]dec-8-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(oxetan-3-yl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one;2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylacetamide; tert-butyl 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)methyl]piperidine-1-carboxylate; 5-chloro-2-({[(3,5-difluoropyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(piperidin-2-yl)methyl]amino}methyl 5-Chloro-2-({[2-oxo-2-(piperidin-1-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}amino)-N-ethyl-N-methylacetamide; 5-Chloro-2-[(4-methyl-3-oxopiperazin-1-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one 5-Chloro-2-{[(pyridin-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(pyrimidin-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(pyrimidin-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(5-methoxypyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[(2,4-dimethyl-3-oxopiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}piperidine-4-carboxylic acid ethyl ester;5-Chloro-2-({1-oxo-2-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperidin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}piperidine-4-carboxylic acid methyl ester; 5-Chloro-2-({[(5-fluoropyridin-2-yl)methyl)-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}piperidine-4-carboxylic acid methyl ester; 5-Chloro-2-{[3-(2-methylpropoxy)azetidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[3-(2-methylpropoxy)azetidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(4-ethoxypiperidin-1-yl)methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(cyclopropylmethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one Spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-hydroxy-4-(trifluoromethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(propan-2-yloxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-fluoroazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline oxazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(methoxymethyl)azetidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(methoxymethyl)azetidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{7-oxa-2-azaspiro[3.5]nonan-2-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-[(4-methoxy-4-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-({3-oxo-1-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)-N,N-dimethyl Acetamide; 5-chloro-2-({[(6-methylpyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(oxacyclohexan-4-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({methyl[(3-methyloxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-2-({[(3-fluorooxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxacyclohexane-4-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(3-methyloxetan-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[methyl(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(oxetan-3-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(4-oxopiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(2-methoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(2,4-dimethoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 5-Chloro-2-{[4-(propan-2-yl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(propan-2-yl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3,3,4-trimethylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[1-(hydroxymethyl)cyclopentyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(2-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f ]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(2-methylpropyl)morpholin-4-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-cyclobutyl-2,2-difluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-ethylmorpholin-4-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(2-cyclohexyl-2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{6-oxa-9-azaspiro[4.5]dec-9-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[1-(oxacyclohexan-2-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2-cyclohexan-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 5-Chloro-2-{[(4,4-difluorocyclohexyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(4,4-difluorocyclohexyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(1r,4r)-4-methoxycyclohexyl]amino}methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5 ,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane-5-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-methoxy-3-methylazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({5-methyl-octahydropyrrolo[3,4-c]pyrrol-2-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[3-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3R)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3S)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-ethoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-(2-hydroxypropane-2-yl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(dimethylamino)ethyl](methyl)amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 3-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)-N,N-dimethylpropanamide; 5-chloro-2-({methyl[2-(morpholin-4-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one 3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-methoxypyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(2,2,2-)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; methyl 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino)acetate;2-[(8aR)-octahydropyrrolo[1,2-a]piperazin-2-ylmethyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(oxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}piperidine-3-carboxylic acid methyl ester; 2-({5-chloro-7-oxo-7,8- 5-Chloro-2-{[(3S)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(oxan-3-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3R)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one 1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3S)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; (3R)-1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9 ,1'-cyclohexane]-2-ylmethyl}piperidine-3-carboxylic acid methyl ester; 5-chloro-2-({[2-(trifluoromethoxy)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-diethylacetamide; (2S)-2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylpropanamide; (2R)-2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylpropanamide; 5-chloro-2-({[2-oxo -2-{[(oxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[({3-oxabicyclo[3.1.0]hexan-6-yl}amino)methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxepan-4-yl)amino]methyl}-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxolan-3-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3,3-difluoro-2-hydroxypropyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(4-cyclopropyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f] Quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,6-dimethyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(3-methyloxolan-3-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(2-methoxyethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aS)-octahydropyrrolo[1,2-a ]piperazin-2-ylmethyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; (3R)-1-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}pyrrolidine-3-carboxylic acid methyl ester; 5-chloro-2-{[4-(2,2-difluoroethyl)piperazin-1-ylmethyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-methyloxolan-3-yl)methyl]amino}methyl)-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3R)-oxacyclohexan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3R)-oxacyclohexan-3-ylmethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3-fluorooxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5, 5-Chloro-2-{[(2,2-difluorocyclopentyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2,2-difluorocyclopentyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[4-(methoxymethyl)oxan-4-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({[(3S)-oxolan-3-ylmethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-4',4'-difluoro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-4',4'-difluoro-2-({[(3S)-oxolan-3-ylmethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9, 1'-cyclohexane]-7-one; 5-chloro-2-{[(1,3-oxazol-2-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(1,3-oxazol-5-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(1,2-oxazol-3-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(1,3 5-Chloro-2-{[(1,2-oxazol-5-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(1,2-oxazol-5-ylmethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5 ,4-f]quinazoline-9,1'-cyclohexane]-2-ylmethoxy}-N,N-dimethylacetamide; 5-chloro-2-[(oxan-4-yloxy)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(1-methylpiperidin-4-yl)oxy]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-[2-(dimethylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-2-(morpholine-4-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-N,N-dimethyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-(4-methylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-N-(2-methoxyethyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f] Quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2-methoxyethyl)-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-N-methyl-N-(oxacyclohexan-4-ylmethyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline oxazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(3R)-3-ethoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylacetamide; 3-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylacetamide}-N,N-dimethylpropionamide; 5-chloro-2-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl-N-methylformamido}acetic acid methyl ester; 5-chloro-N-methyl-N-[2-(methylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-N-[2-(dimethylamino)ethyl]-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-[4-(dimethylamino)piperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(2-methoxyethyl)piperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 2-[(8aR)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-methyl-N-(oxan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-(3-methoxypyrrolidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3R)-3-methoxypiperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(oxacyclohexane-3-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(3S)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline- 9,1'-cyclohexane]-7-one; 5-chloro-2-[(3R)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3S)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-7-oxo-N-[2-(trifluoromethoxy)ethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-2-[(3R)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(4-ethylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(propan-2-yl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[4-(2,2-difluoroethyl)piperazine-1-carbonyl] -7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(piperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-7-oxo-N-[(3R)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo 5-Chloro-2-[4-(2-fluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-N-(2,2-difluorocyclopentyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-[4-(methoxymethyl)oxan-4-yl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -cyclohexane]-2-carboxamide; 5-chloro-N-(3-fluorooxacyclohexan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-N-(2,2-difluoro-3-hydroxypropyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-7-oxo-N-[(3S)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-7-oxo-N-[(3S)-oxolan-3-yl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-7-oxo-N-[(3R)-oxolan-3-yl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-4',4'-difluoro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline oxazolin-9,1'-cyclohexane]-7-one; 2-[(4,4-difluoropiperidin-1-yl)methyl]-5-fluoro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-fluoro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}(methyl)amino )-N,N-dimethylacetamide; 2-({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-ylmethyl}amino)-N,N-dimethylacetamide; 5-chloro-4',4'-difluoro-2-({[(3S)-oxan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3R)-oxan-3-ylmethyl]amino}methyl)-7,8-dihydro -6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3S)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof; or; A compound selected from the group consisting of: 5-Chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-[2-(dimethylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-(morpholine-4-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide 5-Chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-2-(4-methylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(4-methoxypiperidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(4-methoxypiperidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2-methoxyethyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2-methoxyethyl)-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide 1-(4-(5-chloro-2-((3R)-3-ethoxypyrrolidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one); 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylacetamide;3-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl-N-methylformamido}-N,N-dimethylpropanamide; 5-chloro-2-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-{1-5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl-N-methylformamido}acetate; 5-chloro-N-methyl-N- [2-(Methylamino)ethyl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[4-(dimethylamino)piperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]- ]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(2-methoxyethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aR)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-methyl-N-(oxan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1 ,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-(3-methoxypyrrolidine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3R)-3-methoxypiperidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(oxan-3-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-2-[(3S)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3R)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(3S)-3-(methoxymethyl)pyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-7-oxo- N-[2-(trifluoromethoxy)ethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[(3R)-3-methoxypyrrolidine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(4-ethylpiperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(propan-2-yl)piperazine-1-carbonyl]-7,8-dihydro-6 H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[4-(2,2-difluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(piperazine-1-carbonyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one oxazolin-9,1'-cyclohexane]-7-one; 5-chloro-7-oxo-N-[(3R)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-2-[4-(2-fluoroethyl)piperazine-1-carbonyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-N-(2,2-difluorocyclopentyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide;5-Chloro-N-[4-(methoxymethyl)oxan-4-yl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-(3-fluorooxan-4-yl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-N-[4-(methoxymethyl)oxan-4-yl]-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide -N-(2,2-difluoro-3-hydroxypropyl)-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-7-oxo-N-[(3S)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-chloro-7-oxo-N-[(3S)-oxolan-3-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-7-oxo-N-[(3R)-oxolan-3-yl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide; 5-Chloro-4',4'-difluoro-7-oxo-N-[(3R)-oxolan-3-yl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxamide -7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-carboxylic acid methyl ester; 2-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5-chloro-4',4'-difluoro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof; or; A compound selected from the group consisting of: 5-Chloro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(chloromethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(methoxymethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-(hydroxymethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-propyl-7,8-dihydro -6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-ethyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(dimethylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(morpholin-4-yl)methyl]-7 ,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-hydroxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(methylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(cyclopropylamino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; [(Piperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(pyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(2-methoxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-(2-hydroxyethyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(propan-2-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(ethylamino)methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f ]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4,4-difluoropiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-hydroxyethyl)(methyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3,3-difluoroazepine cyclobutane-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3,3-difluoropyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(4-acetylpiperazin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-propionylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline oxazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({2-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(oxetan-3-yl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylacetamide;tert-Butyl 2-{[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl}methyl)amino]methyl}piperidine-1-carboxylate; 5-chloro-2-({[(3,5-difluoropyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(piperidin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-oxo-2- 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N-ethyl-N-methylacetamide; 5-chloro-2-[(4-methyl-3-oxopiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethyl-3-oxopiperazin-1-yl)methyl]-7,8 -dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(pyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(pyrimidin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(5-methoxypyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-4-carboxylic acid ethyl ester; 5-chloro-2-({1-oxo-2-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;2-[(4-acetylpiperidin-1-yl)methyl]-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-4-carboxylate; 5-chloro-2-({[(5-fluoropyridin-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(2-methylpropoxy)azetidine- 1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-ethoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(cyclopropylmethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(cyclopropylmethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; [1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(propan-2-yloxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-fluoroazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-methoxyazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1 '-cyclohexane]-7-one; 5-chloro-2-{[3-(methoxymethyl)azetidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({7-oxa-2-azaspiro[3.5]nonan-2-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(4-methoxy-4-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({3-oxo-1-oxa-8-azaspiro[4.5]dec-8-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)(methyl)amino]-N,N-dimethylacetamide; 5-Chloro-2-({[(6-methylpyridin-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane] -7-one; 5-chloro-2-({methyl[(oxetane-4-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({methyl[(3-methyloxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-fluorooxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane ]-7-one; 5-chloro-2-({[(oxacyclohexane-4-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({2-oxa-7-azaspiro[3.5]nonan-7-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-methyloxetane-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-2-({2-oxa-5-azabicyclo[2.2.1]heptane-5-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(2,2,2-trifluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(oxetan-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-[(4-oxopiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(2-methoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(2,4-dimethoxyphenyl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(propan-2-yl)piperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[1-(hydroxymethyl)cyclopentyl]amino}methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(2-methylpiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[2-(2-methylpropyl)morpholin-4-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f ]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-cyclobutyl-2,2-difluoroethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-ethylmorpholin-4-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2-cyclohexyl-2-hydroxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({6-oxa-9-azaspiro[4.5]dec-9-yl}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[1-(oxacyclohexan-2-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(oxacyclohexan-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-Chloro-2-({[(oxacyclohexan-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; ethyl 2-{5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}acetate; 2-[(4,4-difluoropiperidin-1-yl)methyl]-5-fluoro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-fluoro-2-{[(2-methoxyethyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9, 1'-cyclohexane]-7-one; 5-chloro-2-{[(3-methyl-2-oxobutyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-fluoro-2-[(3-methoxyazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(4,4-difluorocyclohexyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1R,4R 5-Chloro-2-{[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-[(3-methoxy-3-methylazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[(4-methoxypiperidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(dimethylamino)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 5-Chloro-2-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[3-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3R)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one ,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3S)-3-methoxypiperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-ethoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-ethoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(dimethylamino)ethyl](methyl)amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 3-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)(methyl)amino]-N,N-dimethylpropanamide;5-Chloro-2-({methyl[2-(morpholin-4-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 5-Chloro-2-[(3-methoxypyrrolidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-[(5-Chloro-7-oxo-7,8-dihydro- 2-{[(8aR)-octahydropyrrolo[1,2-a]pyrazin-2-yl]methyl}-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(oxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-3-carboxylic acid methyl ester; 2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]acetic acid methyl ester; 5-chloro-2-{[(3S)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(oxan-3-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl -cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-methoxypyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3S)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3R)-3-(methoxymethyl)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;(3R)-1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)piperidine-3-carboxylic acid methyl ester; 2-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methoxy)-N,N-dimethylacetamide; 5-chloro-2-[(oxan-4-yloxy)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(trifluoromethoxy)ethyl]amino}methyl 5-Chloro-2-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{[5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{[3-(dimethylamino)pyrrolidin-1-yl]methyl} ... (2S)-2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylpropanamide; (2R)-2-[({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylpropanamide; 5-chloro-2-({[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5, 5-Chloro-2-{[(oxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(oxacycloheptan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(oxacycloheptan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-{[(3,3-difluoro-2-hydroxypropyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(4-cyclopropyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(2,6-dimethyloxan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxacyclopentane-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3S)-oxacyclopentane-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(3-methyloxacyclopentane-3-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one [1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[4-(2-methoxyethoxy)piperidin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 2-{[(8aS)-octahydropyrrolo[1,2-a]pyrazin-2-yl]methyl}-5-chloro-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f] Quinazoline-9,1'-cyclohexane]-7-one; (3R)-1-({5-chloro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-2-yl}methyl)pyrrolidine-3-carboxylic acid methyl ester; 5-chloro-2-{[4-(2,2-difluoroethyl)piperazin-1-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(3-methyloxolan-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-Chloro-2-({[(3R)-oxacyclohexan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-[({[(3R)-oxacyclohexan-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2-{[(3-fluorooxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-2-{[(2,2-difluoro-3-hydroxypropyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[(2,2-difluorocyclopentyl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[4-(methoxymethyl)oxan-4-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-2-[({[(3S)-oxolan-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1,3-oxazol-2-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-methyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro- -2-{[(1-methylpiperidin-4-yl)oxy]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; 2-[({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl}methyl)(methyl)amino]-N,N-dimethylacetamide; 2-[({5-fluoro-7-oxo-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-2-yl}methyl)amino]-N,N-dimethylacetamide;5-Chloro-4',4'-difluoro-2-{[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-4',4'-difluoro-2-[({[(3S)-oxacyclopentane-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-Chloro-2,4',4'-trimethyl-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]- 7-one; 5-chloro-4',4'-difluoro-2-({[(3S)-oxacyclohexane-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-[(4-methylpiperazin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-[({[(3R)-oxacyclohexane-3-yl]methyl}amino)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one -cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3S)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-4',4'-difluoro-2-({[(3R)-oxolan-3-yl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1,3-oxazol-5-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1 '-cyclohexane]-7-one; 5-chloro-2-({[2-(1,2-oxazol-3-yl)ethyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1,3-oxazol-4-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[(1-methyl-1H-pyrazol-3-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one;5-chloro-2-({[(1,2-oxazol-5-yl)methyl]amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazolin-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof; or; 5'-Chloro-7'-(hydroxymethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-[4-(2-fluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; N-{2-[benzyl(methyl)amino]ethyl}-5'-chloro-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-{[4-(propan-2-yl)piperazin-1-yl]methyl}-7',8' -dihydro-6'H-spiro[cyclohexane-1,9'-furo[23-f]quinazoline]-7'-one; 5'-chloro-2'-{[methyl({[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]methyl})amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; 5'-chloro-2'-(4-methylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(4-ethylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one [2,3-f]quinazoline]-7'-one; 5'-chloro-N-(2-methoxyethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(2-methoxyethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-(piperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-(azetidine-1-carbonyl)-5'- Chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-(pyrrolidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-(morpholine-4- 5'-Chloro-2'-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-[4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-[4-(2,2-difluoroethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-(piperidin-1-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-(morpholin-4-ylmethyl)-7',8 '-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(pyrrolidin-1-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[(4-methylpiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-ethyl-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; Chloro-7'-oxo-N-[2-(propan-2-yloxy)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(4-methoxypiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(4-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-methoxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[ Cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-methyl-N-(2-methylpropyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-cyclopentyl-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(1-hydroxy-3-methylbutan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-N-(1-methylpiperidin-4-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(2-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-[4-(2-hydroxyethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-(3-hydroxypropyl)-7'-oxo-7 ',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(4-hydroxybutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-hydroxyethyl)-7'-oxo-N-propyl-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[2-(pyrrolidin-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9' -furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethylamino)ethyl]-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[3-(1H-imidazol-1-yl)propyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethylamino)ethyl]-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; ]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-hydroxybutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[3-(dimethylamino)propyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 2'-[(8aS)-octahydropyrrolo[1,2-a]piperazine-2-carbonyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-N-methyl-7'-oxo-N-[2-(pyridin-2-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2-cyanoethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2-ethoxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-7'-oxo-N-(oxolane- 2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-methoxyethyl)-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[2-(thien-2-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-cyclopentyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-ethyl-N-(2-hydroxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(3-hydroxypiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-[2-(1H-pyrrol-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide Formamide; 5'-chloro-N-methyl-N-(1-methylpyrrolidin-3-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-formamide; 5'-chloro-N-(3-hydroxy-3-phenylpropyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-formamide; 5'-chloro-2'-[3-(hydroxymethyl)-3-(2-methylpropyl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-N-[(2,3-dimethoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-7'-[2-(trifluoromethyl)-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-7-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[3-(morpholin-4-yl)propyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one formamide; 5'-chloro-N-[(2-methoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[3-(1H-imidazol-1-ylmethyl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2-[4-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperazin-1-yl]acetate; 5'-chloro-N-[( 2,4-dimethoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-methoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2,2-dimethyloxan-4-yl)-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; -[(1-methyl-1H-1,3-benzodiazol-2-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3,5-dimethoxyphenyl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-{5H,6H,7H,8H-imidazo[1,2-a]pyrazine-7-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-[2-(pyridin-2-yl)pyrrolidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-(2-hydroxy-2-phenylethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[2-(2,3-dihydro-1H-indol-1-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-[(2,3-dimethoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-N-[(5-methyl-1H-1,3-benzodiazol-2-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-[3-(trimethyl-1H-pyrazol-4-yl)propyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline] -2'-carboxamide; 5'-chloro-2'-{octahydropyrrolo[1,2-a]piperazine-2-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(5-cyclopropyl-1H-pyrazol-3-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- Quinazoline]-2'-carboxamide; 5'-chloro-N-[(2,4-dimethoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-(1-benzylpyrrolidin-3-yl)-5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(2,3-difluoro-4-methoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-N-{[4-(dimethylamino)phenyl]methyl}-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(1-methyl-1H-imidazol-2-yl)methyl]-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-[4-(pyridin-4-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; N-[(5-tert-butyl 2'-(4-Benzylpiperazine-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1-methylpiperidin-4-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-(3-methoxypiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide Hydrogen-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-methyl-7'-oxo-N-[(trimethyl-1H-pyrazol-4-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(pyridin-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)propyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H -spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(4-methyl-2-phenylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[3-(dimethylamino)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(morpholin-4-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-7'-oxo-N-[2-(pyridin-3-yloxy)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(2-fluoro-4-methoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)azetidine-3-carbonitrile; 5'-Chloro-2'- {3-phenyl-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-7-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-[2-(2-oxopyrrolidin-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-(2,2,6,6-tetramethyloxan-4-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- 2'-carboxamide; 2'-[(1R,5S)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(4-fluorophenoxy)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[2-(1H-pyrazol-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2 '-carboxamide; 5'-chloro-N-[4-(4-hydroxypiperidin-1-yl)phenyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(3,3-dimethyl-2-oxobutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(furan-2-ylmethyl)-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-2'-{4-[2-(dimethylamino)ethyl]piperidine-1-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-[4-(5-chloropyridin-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[(2-methoxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2-hydroxy 5'-Chloro-N-[(4-cyanophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-[3-oxo-4-(propan-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-{[5-(difluoromethoxy)pyridin-2-yl]methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide}-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(oxetane-3-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1R,5S)-6,6-difluorobicyclo[3.1.0]hexane-3-yl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-[2-(2H-1,3-benzo[1-piperazine-1-carbonyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one 5'-Chloro-N-[(4-ethyl-4H-1,2,4-triazol-3-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(4-ethyl-4H-1,2,4-triazol-3-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-[(4-cyano-3-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide;2-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-ylcarboxamido}-N,N-diethylacetamide; 5'-chloro-7'-({6'-methyl-5',6'-dihydro-4'H-spiro[piperidin-4,7'-thieno[2,3-c]pyridine]-1-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(6-methylpyridin-3-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline ]-7'-carboxamide; 5'-chloro-7'-oxo-N-[(trimethyl-1H-imidazol-2-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(5-methylpyridin-3-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-[(5-phenyl-1,2-oxazol-3-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide amide; 2'-{6-azaspiro[2.5]octane-6-carbonyl}-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(oxan-4-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-({6',7'-dihydro-5'H-spiro[piperidin-4,4'-thieno[3,2-c]pyridine]-1-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7 '-one; 5'-chloro-N-(1-methoxy-2-methylpropane-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[1-(pyridin-3-yl)piperidin-4-yl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-({3,4-dihydrospiro[2-benzopyran-1,4'-piperidin]-1'-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-7'-oxo-N-(2-phenoxyethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 3-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylcarboxamido}-N,N-dimethylpropanamide; 5'-chloro-N-[1-(methoxymethyl)cyclopropyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7'-oxo- 7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(cyclobutylmethyl)-7'-oxo-N-(oxolan-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-7'-[4-(furan-2-ylmethyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-7'-oxo-7',8'-dihydro-6 'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[1-(pyridin-2-yl)cyclopropyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(4-methyloxan-4-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-{[1-(ethoxymethyl)cyclopropyl]methyl}-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[ 2'-(4-{bicyclo[2.2.1]heptane-2-yl}piperazine-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(1-methyl-1H-imidazol-5-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-7'-oxo-N-[2-oxo-2-(piperidin-1-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-(3-hydroxyazetidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-oxo-N-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-(3-hydroxyazetidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one -N-[1-(oxacyclohexane-4-yl)cyclopropyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(prop-2-yn-1-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N,N-diethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(1-methyl-2-oxo- 5'-Chloro-2'-[(1R,5S,6S)-6-(pyridin-2-yl)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[(6-fluoropyridin-2-yl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-ethyl-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-{6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-{7,7-difluoro-3-azabicyclo[4.1.0]heptane-3-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-{6,6-difluoro-3-azabicyclo[3.1.0]hexane-3-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-(2,2,2-trifluoroethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-[(5-oxopyrrolidin-2-yl)methyl]-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide amide; 5'-chloro-N-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(4,4-difluorocyclohexyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-{bicyclo[1.1.1]pentan-1-yl}-5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'- Chloro-N-[(1S,3R)-3-fluorocyclopentyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-methyl-7'-oxo-N-(prop-2-en-1-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-7'-oxo-N-(prop-2-yn-1-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-7'-{2-ethyl-1-oxo- 1H,2H,5H,6H,7H,8H-pyrido[3,4-d]pyridazine-6-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; 5'-chloro-N-(1,3-dihydro-2-benzofuran-5-ylmethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[4-(methoxymethyl)oxan-4-yl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-N-cyclobutyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-{9-propionyl-2,9-diazaspiro[5.5]undecane-2-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-methyl-7'-oxo-N-(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- 2'-carboxamide; 5'-chloro-2'-[(1R,5S,6S)-6-(2-methoxyphenyl)-3-azabicyclo[3.1.0]hexane-3-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; N-butyl-5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-{8-ethoxy-2H,3H,4H,5H-pyrido[3,2-f][1,4]oxazepine; -4-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N-[2-(thien-3-yl)ethyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-cyclobutyl-2,2-difluoroethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-propyl-7',8'-dihydro-6'H-spiro[cyclohexane- 1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; (2R)-1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)pyrrolidine-2-carboxylic acid; 5'-chloro-7'-[(1R,6R)-7,7-difluoro-6-methyl-3-azabicyclo[4.1.0]heptane-3-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-methyl-7'-oxo-N-{[4-(propan-2-yl)-4H-1,2,4-triazole- 3-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-({4-oxo-3,4-dihydrospiro[1-benzopyran-2,3'-pyrrolidine]-1'-yl}carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-cyclopropyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-ethyl-7'-oxo-N-propyl-7',8'-dihydro-6' H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-oxo-N-propyl-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(thien-3-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperidine-4-carbonitrile;5'-Chloro-2'-[3-(dimethylamino)pyrrolidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-]quinazoline]-7'-one; N-benzyl-5'-chloro-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(thien-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-methoxyphenyl)methyl ]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(3-hydroxypyrrolidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo-N,N-bis(propan-2-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(furan-2-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H -spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-[2-(hydroxymethyl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-[4-(propan-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-[2-(furan-2-yl)pyrrolidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one [2,3-f]quinazoline]-7'-one; 5'-chloro-N-(3-methylbutyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(2-cyanoethyl)-N-ethyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-7'-oxo-N-(pyridin-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;5'-Chloro-7'-oxo-N-[3-(pyrrolidin-1-yl)propyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-7'-oxo-N-(pentan-3-yl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 2'-(azepane-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-[2-(1H-imidazol-1-yl)ethyl]-7'-oxo- 7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-methyl-7'-oxo-N-(pyridin-3-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-methyl-N-(1-methylpiperidin-4-yl)-7'-oxo-7',8'-dihydro-6' H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-ethyl-1,2-oxazol-5-yl)methyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-(3-methylbutan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-7'-(3-methylpiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide furano[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(dimethylamino)ethyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-7'-(2,2-dimethylmorpholine-4-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[(3-hydroxyphenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide;5'-Chloro-7'-[4-(dimethylamino)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-oxo-N-[3-(2-oxopyrrolidin-1-yl)propyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-2'-(4-methylpiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-oxo-N-(thiophen-3-ylmethyl)- 7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[(3-fluorophenyl)methyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; N-benzyl-5'-chloro-N-(2-hydroxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-N-methyl-7'-oxo-7',8'- dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-(4-cyclohexylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(4-hydroxy-4-phenylpiperidine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[4-(oxolane-2-carbonyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2, 3-f]quinazolin]-7'-one; 5'-chloro-2'-{4-[(dimethylamino)methyl]piperidine-1-carbonyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-yl}carbonyl)-N-methylpiperidine-4-carboxamide; 5'-chloro-N-[2-(4-methoxyphenyl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-carboxamide;5'-Chloro-N-[2-(dimethyl-1,2-oxazol-4-yl)ethyl]-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-Chloro-2'-[4-(1,3-thiazol-2-yl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-N-{[4-(1H-imidazol-1-yl)phenyl]methyl}-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3 -f]quinazoline]-2'-carboxamide; 2'-(4-tert-butylpiperazine-1-carbonyl)-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-[2-(3-methoxyphenyl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(pyrrolidin-1-yl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro- -N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-[4-(morpholin-4-yl)piperidine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[4-(3-methoxyphenyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-oxo- 5'-Chloro-N-(1-hydroxy-3-phenylpropan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(1-hydroxy-3-phenylpropan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(1-hydroxy-3-phenylpropan-2-yl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-Chloro-N-(2H-1,3-benzodioxol-5-ylmethyl)-5'-chloro-N-methyl-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide;3-[1-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperidin-2-yl]propanoic acid methyl ester; 5'-chloro-7'-(4-cyclopentylpiperazine-1-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-yl}carbonyl)piperidin-2-yl]propanoic acid methyl ester furano[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-[4-(2-methylpropionyl)piperazine-1-carbonyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; N-benzyl-5'-chloro-N-(3-hydroxypropyl)-7'-oxo-7',8 '-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-carboxamide; 5'-chloro-N-(2-methoxyethyl)-7'-oxo-N-(thien-2-ylmethyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethylamino)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-{5H,6H,7H-pyrrolo[3,4-b]pyridine-6-carbonyl}-7',8'-dihydro-6'H-spiro [Cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-N-cyclohexyl-N-(2-hydroxyethyl)-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-N-[2-(dimethyl-1,3-thiazol-2-yl)ethyl]-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-carboxamide; 5'-chloro-2'-({[(3R,4R)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1, 9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[2-(2-hydroxyethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-[(3-oxopiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({[(1-methyl-1H-pyrazol-3-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-{[(2-methoxyethyl)(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperidine-4-carbonitrile; 5'-chloro-2'-{[(2-hydroxyethyl)(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(pyridine-4 -yl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[(oxan-4-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-[(8aS)-octahydropyrrolo[1,2-a]piperazin-2-ylmethyl]- 5'-Chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[(oxolan-2-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 3-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}(ethyl)amino)propionitrile; 5'-chloro-2'-{[(pyridin-2-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane- 1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[(2-methylsulfonylethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 2'-{[benzyl(2-hydroxyethyl)amino]methyl}-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-{[(furan-2-ylmethyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-[(4-methoxypiperidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 2'-[(4-acetyl-1,4-diazaheptan-1-yl)methyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-{[4-(2-hydroxyethyl)piperazin-1-yl ]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({4-[(dimethylamino)methyl]piperidin-1-yl}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-{[4-(oxolane-2-carbonyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({[(5-oxopyrrolidin-2-yl)methyl](propan-2-yl)amino}methyl)-7 ',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{5H,6H,7H,8H-imidazo[1,2-a]pyrazin-7-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7 '-one; 5'-chloro-2'-({[3-(2-oxopyrrolidin-1-yl)propyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline] [2,3-f]quinazolin]-2'-ylmethyl}-N-methylpiperidine-4-carboxamide; 5'-chloro-2'-{[(3-hydroxypropyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}piperidine-3-carboxamide;3-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}(methyl)amino)-N-methylpropanamide; 5'-chloro-2'-[{(1R,5S,6S)-6-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[ethyl(2-hydroxyethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one Quinazoline]-7'-one; 5'-chloro-2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[(3-hydroxypiperidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(2-hydroxyethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[ (2R,6S)-2,6-dimethylmorpholin-4-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(4-ethyl-4H-1,2,4-triazol-3-yl)methyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-{2-oxa-6-azaspiro[3.5]nonan-6-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one ketone; 5'-chloro-7'-{[ethyl(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(5-cyclopropyl-1H-pyrazol-3-yl)methyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[3-(dimethylamino)propyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2-(4-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperazin-1-yl)pyridine-3-carbonitrile; 5'-Chloro-2'-{[3-(1H-imidazol-1-ylmethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one ketone; 5'-chloro-2'-{[4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(2-methoxyethyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[methyl(pyridin-3-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 4 -{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}-thiomorpholine-1,1-dione; 5'-chloro-2'-{[(4-hydroxy-2-methylbutan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 4-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperazine-1-carboxaldehyde; 5'-chloro-2'-{[4-( [({[4-(morpholin-4-yl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 4-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}-N,N-dimethylpiperazine-1-carboxamide; 5'-chloro-2'-[({[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]methyl}amino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-{[3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}azetidine-3-carbonitrile; 4-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}}amino)-sulfurized cyclopentane-1,1-dione; 5'-chloro-2'-[(4-methylsulfonylpiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 7-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}-5H,6H,7H,8H-imidazo[1,2-a]pyrazine-2-carboxylic acid ethyl ester; 2'-{6-azaspiro[2.5]octan-6-ylmethyl}-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'- furano[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[(2,2,2-trifluoroethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{octahydropyrrolo[1,2-a]piperazin-2-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[4-(furan-2-ylmethyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one quinazolin]-7'-one; 5'-chloro-2'-{[methyl(propan-2-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 3-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}amino)-tetrahydrothiophene-1,1-dione; 5'-chloro-2'-{[4-(pyridin-3-ylmethyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-Chloro-2'-[(4-methyl-1,4-diazepan-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[4-(dimethylamino)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-({methyl[(trimethyl-1H-pyrazol-4-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7' -one; 5'-chloro-7'-{[3-oxo-4-(propan-2-yl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-{[(2,2-dimethyloxan-4-yl)(ethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[4-(pyrrolidine-1-carbonyl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3 -f]quinazolin]-7'-one; 5'-chloro-2'-{[(1,3-oxazol-5-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-[(propylamino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-({[(1-methyl-1H-pyrazol-5-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one ketone; 5'-chloro-2'-{[4-(oxetan-3-yl)piperazin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({methyl[2-(pyridin-2-yl)ethyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[(2-methoxyethyl)(methyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one;5'-Chloro-2'-{5H,6H,7H-pyrrolo[3,4-b]pyridin-6-ylmethyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-({[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-({[2-(dimethylamino)ethyl](ethyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one 5'-Chloro-2'-[(3-hydroxypyrrolidin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-[({[6-(morpholin-4-yl)pyridin-3-yl]methyl}amino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[methyl(propyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline] -7'-one; 5'-chloro-2'-({[3-(3,5-dimethyl-1H-pyrazol-1-yl)propyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-7'-[(2,2-dimethylmorpholin-4-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-[(4-ethylpiperazin-1-yl)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]- 7'-one; 5'-chloro-2'-({[(3-ethyl-1,2-oxazol-5-yl)methyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-2'-{[methyl(pyridin-2-ylmethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}piperidine-4-carboxamide;5'-Chloro-2'-({[2-(2-oxopyrrolidin-1-yl)ethyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-[({[1-(ethoxymethyl)cyclopropyl]methyl}amino)methyl]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-Chloro-2'-({[2-(dimethyl-1,2-oxazol-4-yl)ethyl](methyl)amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; N-( 1-{5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-2'-ylmethyl}piperidin-4-yl)acetamide; 5'-chloro-2'-{[2-(hydroxymethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-{[methyl(1-methylpiperidin-4-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({6,6-dimethyl-3-azabicyclo[3.1.0] 5'-Chloro-2'-({[(1-methyl-1H-imidazol-2-yl)methyl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[3-(hydroxymethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-7'-{[(2-hydroxyethyl)(propyl)amino]methyl}-7',8'-dihydro-6' H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 2-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}(methyl)amino)ethyl acetate; 2'-[(3-aminopyrrolidin-1-yl)methyl]-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; N-{2-({5'-chloro-7'-oxo-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-2'-ylmethyl}amino)ethyl}acetamide;5'-Chloro-2'-{[4-(hydroxymethyl)piperidin-1-yl]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-{[(piperidin-3-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-Chloro-2'-{[(pyrrolidin-3-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-benzoyl-5'-chloro-7',8'-dihydro-6 'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-(pyridine-4-carbonyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 2'-acetyl-5'-chloro-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(3S,4R)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one ; 5'-chloro-2'-{[(3-fluorooxan-4-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(3R)-oxolan-3-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 5'-chloro-2'-({[(3S)-oxolan-3-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; 7'-({[(3R,4S)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-({[(3S,4R)-3-methoxyoxan-4-yl]amino}methyl)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one; 5'-chloro-7'-{[(2-methoxyethyl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazolin]-7'-one;5'-chloro-2'-{[(oxetane-3-yl)amino]methyl}-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-furo[2,3-f]quinazoline]-7'-one; and pharmaceutically acceptable salts thereof. ; 11. The substance of claim 8, wherein the inhibitor is a member selected from the group consisting of compounds having CAS Registry Numbers 2266633-30-9; 2266633-88-7; 2266633-90-1; 2266633-95-6; 2266634-01-7; 2266634-08-4; and 2266637-12-9 assigned by Chemical Abstracts Service (CAS).

12. The compound of claim 8, which is selected from: 5-chloro-2-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-[(3-methoxy-3-methylazetidin-1-yl)methyl]-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[3-(hydroxymethyl)pyrrolidin-1-yl] methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-({[2-(dimethylamino)ethyl](methyl)amino}methyl)-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; 5-chloro-2-{[methyl(oxacyclohexan-4-yl)amino]methyl}-7,8-dihydro-6H-spiro[[1,3]oxazolo[5,4-f]quinazoline-9,1'-cyclohexane]-7-one; and pharmaceutically acceptable salts thereof.

13. A pharmaceutical composition, characterized in that It comprises at least one PDE7 inhibitor according to any one of claims 1 to 12.

14. The pharmaceutical composition according to claim 13, characterized in that It comprises (i) at least one PDE7 inhibitor according to claims 8 and 9, or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, polymorph, ester, ether, enantiomer, prodrug, or metabolite thereof, and at least one pharmaceutically acceptable diluent or excipient, or (ii) at least one compound of the formula according to claims 8, 9, 10, 11 and 12, or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, polymorph, ester, ether, enantiomer, prodrug, or metabolite thereof, and at least one pharmaceutically acceptable diluent or excipient.

15. Use of a compound having phosphodiesterase-7 inhibitory activity (PDE7 inhibitor) for preparing a medicament for treating and preventing chronic fatigue, exhaustion and / or exertion intolerance, preferably, the PDE7 inhibitory compound is in the form of IC 50 <50μM, preferably IC 50 ≤1μM, more preferably IC 50 0.1 to 600 nM, particularly preferably IC 50 From about 0.2 to about 100 nM, and more preferably from about IC 50 The enzyme activity of PDE7 (PDE7A, PDE7B, or PDE7A and PDE7B) is inhibited at about 1 to about 100 nM.

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