KR20140118141A - Novel 5-sulfonylamino-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one compounds having inhibitory activity of serotonine 5-HT6 - Google Patents

Abstract

The present invention relates to a novel 5-sulfonylamino-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one compound having an inhibitory activity for 5-HT6, which is one of serotonin subtypes, and a pharmaceutical composition comprising the compound as an active ingredient. Since the novel compound of the present invention has 5-HT6 inhibitory activities, the compound can be used for diagnosing, preventing, and treating central nervous system (CNS) diseases such as Alzheimer′s disease (AD), attention deficit disorder (ADHD), epilepsy, depression, obesity, schizophrenia, sleep disorders, and pain disorders.

Description

5-sulfonylamino-5,6-dihydro-1H-pyrazolo [3,4-c] pyridin-7 (4H) -one compound having serotonin 5-HT6 inhibitory activity {Novel 5-sulfonylamino- -dihydro-1H-pyrazolo [3,4-c] pyridin-7 (4H) -one compounds having inhibitory activity of serotonine 5-HT6}

The present invention relates to novel 5-sulfonyl-amino-5,6-dihydro -1 H having an inhibitory activity with respect to one of the 5-HT ₆ serotonin subtypes of the pyrazolo [3,4- c] pyridin-7 (4 H ) -one compound and a pharmaceutical composition comprising the compound as an active ingredient.

Recent improvements in living standards and advances in health and medical technology have led to an increase in the average life span and a surge in the elderly population. Therefore, as the population structure becomes aged, the geriatric dementia, which is a degenerative neurological disorder commonly observed in the elderly, is becoming a serious issue. In addition, due to the stress of complex social life, depression and obesity increase in population are reaching serious social level. The most common diseases in the aging industrial society are cranial nervous system diseases except cancer. New drugs are being developed for various biological targets to overcome cranial nerve-related diseases, among which serotonin receptor development is an important target.

Serotonin (5-hydroxytryptamine, 5-HT) receptors are distributed throughout the human and animal body and play an important role in physiological and behavioral functions. There are currently about 15 genetically distinct 5-HT receptor subtypes cloned, each subtype exhibiting a unique distribution and various preferences and correlations to the ligand.

According to data reported in 1993, the human 5-HT ₆ receptor and the mouse 5-HT ₆ receptor were reported to consist of 440 and 438 amino acid glycoproteins, respectively. The 5-HT ₆ receptor is a G-protein coupled receptor (GPCR) of the Gαs-protein family that binds positively to cyclic adenosine monophosphate (c-AMP), including the nucleus accumbens, (striatum, hippocampus), and the posterior tubercle of the brain (olfactory tubercle of the brain). Since 5-HT ₆ receptors are distributed in the central nervous system and have a strong affinity for antipsychotics and antidepressants, they are regarded as a major target for antipsychotic treatment. Especially, as the side effects related to the peripheral nervous system are relatively rare, It is recognized as a target. The 5-HT ₆ receptor is mainly distributed in the brain region, which is closely related to cognitive function and memory, and interferes with acetylcholine (ACh-) and glutamate mediated neurotransmission to promote the cognitive function process .

Drugs with an inhibitory effect on the 5HT ₆ receptor are the treatment of memory and cognitive impairment in Alzheimer's disease (AD) [Johnson CN et al Drug Discov . Today Therapeutic strategies 2004, 1 (1 ), 13-19], sleep regulation [Stephen R, Morality et al SLEEP 2008, 31 (1), 34-44], metabolic disorders and obesity [Heal D. J et al, Pharmacol . Ther 2008 , 117 ( 2 ), 207-231).

There are no commercially available drugs as selective inhibitors of the 5-HT ₆ receptor. SGS518, developed by Saegis Pharmaceutical Inc., SB-742457, developed by Glaxo Smith Kline, and SAM531, developed by Wyeth, respectively, are used as treatments for schizophrenia and Alzheimer's disease It is under clinical Phase II trials. PRX-07034, developed by EPIX Pharmaceutical Inc., is in Phase 1 clinical trial for the treatment of obesity, schizophrenia and dementia.

On the other hand, medical imaging tests contribute greatly to diagnosis and treatment of patients. In recent years, with the introduction of reporter gene technology, molecular images that can image molecular and cellular changes in vivo have been attracting attention. Molecular imaging is a non-invasive method of imaging life phenomena in the living organism's cells or molecular units. It can help diagnose diseases by imaging minute functional differences in the initial state where no anatomical changes have occurred have. Thus, molecular imaging provides early detection and treatment of pre-disease conditions, presents new possibilities in the development of therapeutic agents, early evaluation of post-treatment response, minimizing the toxicity of treatment and tailor-made treatment for each patient . Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are used to obtain these images. Molecular imaging using nuclear medicine techniques such as SPECT and PET has developed at a very rapid rate to evaluate the function of the central nervous system and is indeed a useful technique in basic medical research and clinical practice. Particularly, studies for developing a radioactive probe for PET to image the accumulation of substances causing Alzheimer's disease are being actively carried out. Therefore, if a compound capable of specifically binding to 5-HT ₆ receptor and exhibiting 5-HT ₆ inhibitory activity is developed, it can be used not only as a therapeutic agent for central nervous system diseases caused by the activity of 5-HT ₆ , It is also very useful as a reagent.

The problem to be solved by the present invention is a novel 5-sulfonic having the inhibitory activity of the 5HT ₆ -5-5,6-dihydro -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - On compounds.

Another object to be solved by the present invention is to provide a process for the preparation of 5-sulfonylamino-5,6-dihydro- 1H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) And to provide a pharmaceutical composition for the prevention and treatment of diseases of the central nervous system (CNS).

Another object of the present invention 5-sulfonyl-amino-5,6-dihydro -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - the compound on 5-HT ₆ As an early diagnosis reagent for a central nervous system disease caused by the activity of the enzyme.

In order to achieve the above object, the present invention provides a 5-sulfonylamino-5,6-dihydro- 1H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) Or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

In Formula 1,

R ₁ is a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl, or substituted or unsubstituted piperidinyl Lt; / RTI >

R ₂ is a hydrogen atom, a C _{1 to} C ₆ alkyl group, a naphthalenyl group, or a substituted alkyl group having 1 to 3 substituents selected from halo, C _{1 to} C ₆ alkyl, C _{1 to} C ₆ alkoxy, and C _{1 to} C ₆ haloalkyl A substituted or unsubstituted phenyl group,

n represents an integer of 0 to 6;

The present invention also relates to 5-sulfonylamino-5,6-dihydro- 1H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) Characterized by a pharmaceutical composition useful as a 5HT ₆ inhibitor comprising an acceptable salt thereof as an active ingredient.

The present invention also relates to 5-sulfonylamino-5,6-dihydro- 1H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) The use of an acceptable salt compound thereof as a diagnostic reagent for a central nervous system disease caused by the activity of 5-HT ₆ .

The compounds of the present invention, by specifically binding to the 5HT ₆ receptor inhibits the activity of the 5HT _6. That is, the compounds of this invention by inhibiting the activity of the 5HT ₆ in vivo, increase of acetylcholine and, promotes long-term storage and GABA or glutamic acid salt secretion known to play an important role in cognitive functions, the dopamine and Nord Pinero Perrin Cognitive function can be improved by controlling cranial nerves that are important for cognitive function. The compounds of the present invention specifically bind to the 5HT ₆ receptor and thus can be used as reagents for early diagnosis of diseases caused by the activity of 5HT ₆ .

Accordingly, the present invention compound is cranial nerve diseases caused by the 5HT ₆ activity, in particular Alzheimer's (AD), attention deficit disorder (ADHD), epilepsy, premature depression, obesity, schizophrenia, sleep disorders, pain disorders, such as disorders Diagnosis, prevention and treatment.

The term 'treatment' in the present invention means to stop or delay the progression of a disease when used in an object having an onset symptom.

In addition, the 'pharmaceutical composition' in the present invention may include a pharmaceutically acceptable carrier, diluent, excipient, or a combination thereof together with the compound of the present invention if necessary. The term "carrier" refers to a substance that facilitates the addition of a compound into a cell or tissue. The term 'diluent' is defined as a substance that not only stabilizes the biologically active form of the compound of interest but also dilutes in water to dissolve the compound. The term " pharmaceutically acceptable " means a property that does not impair the biological activity and physical properties of the compound.

Other terms and abbreviations used herein can be interpreted as commonly understood by a person skilled in the art to which the present invention belongs, unless otherwise defined.

The present invention is described in more detail as follows.

The invention serotonin 5-HT to have a _6-inhibiting activity for 5-sulfonyl-amino-5,6-dihydro-1 represented by the formula -1 H - pyrazolo [3,4- c] pyridin-7 (4 H) - one compound with the compound the present invention relates to a medicinal use which use an early diagnostic reagent, or a drug for the prevention and treatment of diseases caused by the activity of the 5HT _6.

[Chemical Formula 1]

In Formula 1,

R ₁ is a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl, or substituted or unsubstituted piperidinyl Lt; / RTI >

R ₂ is a hydrogen atom, a C _{1 to} C ₆ alkyl group, a naphthalenyl group, or a substituted alkyl group having 1 to 3 substituents selected from halo, C _{1 to} C ₆ alkyl, C _{1 to} C ₆ alkoxy, and C _{1 to} C ₆ haloalkyl A substituted or unsubstituted phenyl group,

n represents an integer of 0 to 6;

In the compound represented by the formula (1) according to the present invention, preferably, R ₁ is a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkoxycarbonyl, 3-substituted or unsubstituted phenyl group, R ₂ is a C ₁ -C ₆ alkyl group, and n is 0.

In the compound represented by Formula 1 according to the present invention, preferably, R ₁ is a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl And R ₂ represents a phenyl group substituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl, Or an unsubstituted phenyl group, and n is 0.

In the compound represented by Formula 1 according to the present invention, preferably, R ₁ is a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl And R ₂ represents a phenyl group substituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl, Or an unsubstituted phenyl group, and n is 1.

In the compound represented by Formula 1 according to the present invention, preferably, R ₁ is a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl Or a substituted or unsubstituted piperidinyl group wherein R ₂ is substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl; A substituted phenyl group, and n is 0.

In the compound represented by Formula 1 according to the present invention, preferably, R ₁ is a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl Or a substituted or unsubstituted piperidinyl group wherein R ₂ is substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl; A substituted phenyl group, and n is 1.

In the compound represented by Formula 1 according to the present invention, preferably, R ₁ is a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl A substituted or unsubstituted piperidinyl group, R ₂ is a naphthalenyl group, and n is 1.

The compounds represented by Formula 1 according to the present invention may be any of compounds represented by the following Chemical Formulas 1 to 32,

Compound No. 1; 3-benzenesulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 2; 3- (3-benzene pool Luo) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 3; 3- (3-triethoxysilylpropyl pool Luo methyl benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 4; 3- (3-methoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 5; 3- (2,5-dimethoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 6; 3- (2,4-benzenesulfonyl a full Luo) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - On

Compound No. 7; 3- (2-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 8; 3- (4-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 9; 3- (3-trimethyl benzene sulfonyl pool Luo) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -On

Compound No. 10; Dihydro-6- p -methoxyphenyl-1 H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) -one

Compound No. 11; 3- (2,5-dimethoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -On

Compound No. 12; 3- (2,4-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H )-On

Compound No. 13; 3-benzenesulfonylamino-5,6-dihydro-6- p -methoxyphenyl-1 H -pyrazolo [3,4- c ] pyridin-7 ( 4H )

Compound No. 14; 3- (3-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 15; 3- (2-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 16; 3- (4-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 17; 3-ethyl-sulfonylamino-5,6-dihydro-6-phenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 18; 3- (2,6-dichlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 19; 3- (6-methyl-benzene 2-pool Luo) sulfonyl-amino-5,6-dihydro-6-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -On

Compound No. 20; 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 21; 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 22; 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-benzyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 23; 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-benzyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 24; 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 25; 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - On

Compound No. 26; 3- (1-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 27; 3- (2-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 28; 3- (2-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 29; 3- (4- tert- butyl-benzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 30; 3- (5-methyl-benzene 2-pool Luo) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H )-On

Compound No. 31; 3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one

Compound No. 32; 3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one.

In addition, the compound represented by Formula 1 according to the present invention may form pharmaceutically acceptable salts by a conventional method in the art. Salts are useful as acid addition salts formed by pharmaceutically acceptable free acids. The expression pharmaceutically acceptable salt means a salt which is relatively non-toxic to the patient and has a harmless effective action, and a side effect caused by this salt does not impair the beneficial effect of the base compound of the compound represented by the above formula (1) . As these salts, inorganic acids and organic acids can be used. Examples of the inorganic acid include sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, and hydroiodic acid. Examples of the organic acid include organic acids such as tartaric acid, formic acid, citric acid, acetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, lactic acid, malonic acid, malic acid, salicylic acid, succinic acid, oxalic acid, propionic acid, Organic acids and sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p -toluenesulfonic acid, and naphthalenesulfonic acid.

The addition salt according to the present invention can be prepared by a conventional method, and the addition salt can be easily produced by a person skilled in the art based on the structure of the above-mentioned formula (1) without further explanation. For example, by dissolving the compound represented by the above formula (1) in a water-miscible organic solvent such as acetone, methanol, ethanol, acetonitrile or the like and adding an excess amount of an organic acid or by adding an aqueous acid solution of an inorganic acid to precipitate or crystallize . Subsequently, in this mixture, a solvent or an excess acid is evaporated and dried to obtain an additional salt, or the precipitated salt may be produced by suction filtration.

In addition, the compound represented by Formula 1 according to the present invention includes not only pharmaceutically acceptable salts, but also all salts, isomers, hydrates and solvates which can be prepared by conventional methods. Hereinafter, unless otherwise stated, the compound represented by Formula 1 having the inhibitory activity of 5HT ₆ includes pharmaceutically acceptable salts, isomers, hydrates and solvates thereof, Should be construed as being included in the scope of the present invention.

Meanwhile, the compound represented by Formula 1 according to the present invention has 5-HT ₆ binding ability and inhibitory activity. Thus, the compounds of the present invention inhibit 5-HT ₆ activity in the body, thereby increasing acetylcholine, promoting the secretion of GABA or glutamate, which is known to play an important role in long-term memory and cognitive function, and dopamine and norepinephrine Cognitive function can be improved by controlling cranial nerves important for cognitive function. Accordingly, the compounds of the present invention are useful for the treatment and prophylaxis of neurological diseases caused by problems of cognitive function-controlled neurons, particularly diseases such as Alzheimer's (AD), Attention Deficit Hyperactivity Disorder (ADHD), epilepsy, depression, obesity, schizophrenia, Diagnosis, prevention and treatment.

The pharmaceutical composition of the present invention, which is used for the purpose of prevention and treatment of cerebral neurological diseases, can be produced by adding a conventional non-toxic pharmaceutically acceptable carrier, adjuvant, excipient, etc. to the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof The pharmaceutical preparations can be formulated into tablets, capsules, troches, solutions, suspensions, etc., for oral administration or parenteral administration.

Examples of the formulations for oral administration include tablets, pills, light / soft capsules, liquids, suspensions, emulsions, syrups, granules, elixirs and the like. These formulations may contain, in addition to the active ingredient, a diluent such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine, a lubricant such as silica, talc, stearic acid and its magnesium or calcium salt and / Or polyethylene glycol). The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, optionally mixed with starch, agar, alginic acid or its sodium salt The same disintegrating or boiling mixture and / or absorbing agent, coloring agent, flavoring agent, and sweetening agent.

Examples of the formulations for parenteral administration include injections such as subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. In this case, in order to formulate the formulation for parenteral administration, the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof may be mixed with water or a stabilizer or a buffer to prepare a solution or suspension, .

The composition may be sterilized as needed or may contain other therapeutically useful substances such as preservatives, stabilizers, wettable or emulsifying accelerators, adjuvants such as salts and / or buffers for controlling osmotic pressure, and other therapeutically useful substances, Granulation, or coating method.

The administration dose of the compound represented by Formula 1 to the human body may be varied depending on the patient's age, weight, sex, dosage form, health condition, and disease severity. When the present compound is administered alone to an adult, the dosage administered by route of administration is 0.0001 to 50 mg / kg body weight, and may be, for example, 0.01 to 1 mg / kg body weight in the range of 0.001 to 10 mg / kg body weight. have. These doses may be administered one to five times a day. For intravenous injection, the appropriate daily dose is 0.0001 to 1 mg / kg body weight, preferably 0.0001 to 0.1 mg / kg body weight. The daily dose may be administered as a single dose or according to a divided dose schedule.

In addition, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be used as a reagent for early diagnosis of central nervous system diseases, and may be used in a probe for imaging of SPECT, PET and the like.

The present invention as described above will be described in more detail through the following examples, preparation examples and experimental examples. It should be understood, however, that the following examples, preparation examples, and examples are illustrative of the present invention only and are not intended to limit the scope of the present invention, and various changes and modifications may be made within the scope and spirit of the present invention. Will be apparent to those of ordinary skill in the art.

In addition, those skilled in the art will be able to prepare the desired compound by various methods based on the structure of Formula 1, and these methods should be construed as falling within the scope of the present invention do. That is, the compounds of the present invention may be prepared by any combination of the synthesis methods described in the following examples or the various synthetic methods disclosed in the prior art, which are understood to be within the scope of the present invention, The method is not limited by the concrete examples below.

[Example]

Example 1: 3-benzenesulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (Compound No. 1)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (53.4 mg, 0.220 mmol) and DMAP (2.9 mg , 0.024 mmol) was dissolved in methylene chloride, and anhydrous pyridine (19.6 μL, 0.242 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, benzenesulfonyl chloride (31 L, 0.242 mmol) was added and the mixture was stirred at room temperature for 3.5 hours. Methylene chloride was added to the reaction mixture, and the organic layer was separated and washed with water. The organic layer was dried over anhydrous magnesium sulfate and filtered, and then the solution was removed under reduced pressure to obtain 58 mg (0.152 mmol, 69%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.49 (s, 1H, NH), 10.24 (s, 1H, NH), 7.74 (d, J = 7.3 Hz, 2H), 7.66-7.54 (m, 3H), 7.21 (s, 4H), 3.86 (t, J = 6.4 Hz, 2H), 2.69 (t, J = 6.3 Hz, 2H), 2.30 (s, 3H)

¹³ C NMR (DMSO, 75 MHz):? 157.9, 141.5, 140.7, 140.0, 135.8, 134.3, 133.1, 129.6, 129.5, 127.2, 126.0, 115.9, 51.8, 21.0, 20.0

Example 2: 3- (3-benzene pool Luo) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (Compound No. 2)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (108.4 mg, 0.447 mmol) and DMAP (6 mg , 0.049 mmol) was dissolved in methylene chloride, and anhydrous pyridine (39.8 μL, 0.492 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-fluorobenzenesulfonyl chloride (65.4 μL, 0.492 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. The resulting solid was filtered and washed with methylene chloride and diethyl ether to obtain 77.3 mg (0.193 mmol, 43.2%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.5 (s, 1H, NH), 10.41 (s, 1H, NH), 7.65-7.50 (m, 4H), 7.24-7.18 (m, 4H), 3.89 (t J = 6.6 Hz, 2H), 2.74 (t, J = 6.6 Hz, 2H), 2.30

^{13 C NMR (DMSO, 75 MHz} ): δ 163.6, 160.3, 157.8, 141.2, 140.0, 135.9, 134.4, 131.9, 129.6, 126.0, 123.5, 120.5, 116.0, 114.0, 51.8, 21.0, 20.0

Example 3 3- (3-trimethyl benzene sulfonyl pool Luo) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin-7 (4 H ) -one (Compound No. 3)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (112.1 mg, 0.463 mmol) and DMAP (6.2 mg , 0.051 mmol) was dissolved in methylene chloride, and anhydrous pyridine (41.2 μL, 0.509 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3- (trifluoromethyl) benzenesulfonyl chloride (81.6 μL, 0.509 mmol) was added thereto, followed by stirring at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to obtain 37.7 mg (0.084 mmol, 18.1%) of the target compound as a white solid.

_{^{1 H NMR (CDCl 3, 300}} MHz): δ 13.58 (s, 1H, NH), 9.86 (s, 1H, NH), 7.96 (s, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.45 2H), 2.42 (s, 3H), 2.32 (s, 3H)

¹³ C NMR (CDCl ₃ , 75 MHz): δ 157.8, 141.3, 140.4, 138.4, 136.8, 134.5, 131.2, 130.7, 130.2, 129.4, 128.8, 128.7, 124.9, 124.1, 115.5, 51.8, 21.1, 20.0

Example 4 3- (3-methoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - One (Compound No. 4)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (129.9 mg, 0.536 mmol) and DMAP (7.2 mg , 0.059 mmol) was dissolved in methylene chloride, and anhydrous pyridine (47.6 μL, 0.589 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-methoxybenzenesulfonyl chloride (83.4 μL, 0.589 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The solid obtained by filtration was washed with MeOH and diethyl ether to obtain 145 mg (0.352 mmol, 65.6%) of the title compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.5 (s, 1H, NH), 10.24 (s, 1H, NH), 7.48 (t, J = 7.9 Hz, 1H), 7.31-7.15 (m, 7H), 3.86 (t, J = 6.6 Hz , 2H), 3.79 (s, 3H), 2.71 (t, J = 6.6 Hz, 2H), 2.30 (s, 3H)

^{13 C NMR (DMSO, 75 MHz} ): δ 159.6, 157.8, 141.9, 141.5, 140.0, 135.8, 134.3, 130.7, 129.6, 126.0, 119.2, 118.8, 115.9, 112.3, 56.0, 51.8, 21.0, 20.0

Example 5: 3- (2,5-dimethoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin-7 (4 H ) -one (Compound No. 5)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (104.2 mg, 0.430 mmol) and DMAP (5.7 mg , 0.047 mmol) was dissolved in methylene chloride, and anhydrous pyridine (38.3 μL, 0.473 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 2,5-dimethoxybenzenesulfonyl chloride (111.9 mg, 0.473 mmol) was added and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to obtain 63.3 mg (0.143 mmol, 33.3%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.42 (s, 1H, NH), 9.87 (s, 1H, NH), 7.23-7.15 (m, 7H), 3.87 (t, J = 6.6 Hz, 2H), 3.83 (s, 3H), 3.71 (s, 3H), 2.74 (t, J = 6.6 Hz, 2H), 2.30 (s, 3H)

^{13 C NMR (DMSO, 75 MHz} ): δ 157.9, 152.5, 151.1, 141.5, 140.0, 135.8, 134.1, 129.5, 128.8, 126.0, 119.9, 115.8, 114.9, 114.7, 56.9, 56.2, 51.8, 21.0, 20.0

Example 6. 3- (2,4-benzenesulfonyl a full Luo) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin-7 ( 4H ) -one (Compound No. 6)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (108.5 mg, 0.448 mmol) and DMAP (6 mg , 0.049 mmol) was dissolved in methylene chloride, and anhydrous pyridine (39.9 μL, 0.493 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 2,4-difluorobenzenesulfonyl chloride (66.3 μL, 0.493 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The solid obtained by filtration was washed with methanol and diethyl ether to give 59.4 mg (0.142 mmol, 31.7%) of the title compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.53 (s, 1H, NH), 10.56 (s, 1H, NH), 7.86-7.78 (m, 1H), 7.54 (t, J = 8.6 Hz, 1H), 7.28-7.15 (m, 5H), 3.89 (t, J = 6.6 Hz, 2H), 2.77 (t, J = 6.6 Hz, 2H), 2.30 (s, 3H)

¹³ C NMR (DMSO, 75 MHz):? 157.8, 140.8, 140.0, 135.9, 134.3, 132.5, 132.4, 129.6, 126.0, 120.8, 116.2, 112.7, 106.7, 106.3, 51.8, 21.0,

Example 7 3- (2-benzenesulfonyl pool Luo) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -One (Compound No. 7)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (116.8 mg, 0.482 mmol) and DMAP (6.5 mg , 0.053 mmol) was dissolved in methylene chloride, and anhydrous pyridine (42.9 μL, 0.530 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 2-fluorobenzenesulfonyl chloride (70.2 μL, 0.530 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to give 73.1 mg (0.183 mmol, 37.9%) of the desired compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.51 (s, 1H, NH), 10.49 (s, 1H, NH), 7.79-7.66 (m, 2H), 7.46-7.40 (m, 1H), 7.35 (t , J = 7.6 Hz, 1H) , 7.24-7.15 (m, 4H), 3.88 (t, J = 6.6 Hz, 2H), 2.75 (t, J = 6.6 Hz, 2H), 2.30 (s, 3H)

^{13 C NMR (DMSO, 75 MHz} ): δ 160.5, 157.8, 157.1, 140.9, 140.0, 135.9, 134.3, 130.4, 129.6, 128.6, 126.0, 125.2, 117.7, 116.1, 51.8, 21.0, 19.9

Example 8 3- (4-benzenesulfonyl pool Luo) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -One (Compound No. 8)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (206.3 mg, 0.851 mmol) and DMAP (11.5 mg , 0.094 mmol) was dissolved in methylene chloride, and anhydrous pyridine (75.7 μL, 0.936 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 4-fluorobenzenesulfonyl chloride (198.7 mg, 1.021 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The obtained solid was washed with methylene chloride and diethyl ether to obtain 188 mg (0.469 mmol, 55.2%) of the title compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.52 (s, 1H, NH), 10.28 (s, 1H, NH), 7.80 (dd, J = 5.2, 8.5 Hz, 2H), 7.41 (t, J = 8.7 Hz, 2H), 7.24-7.18 (m , 4H), 3.88 (t, J = 6.5 Hz, 2H), 2.73 (t, J = 6.5 Hz, 2H), 2.30 (s, 3H)

^{13 C NMR (DMSO, 75 MHz} ): δ 166.4, 163.0, 157.8, 141.4, 140.0, 135.8, 134.4, 130.3, 130.2, 129.6, 126.0, 116.8, 116.5, 51.8, 21.0, 20.0

Example 9 3- (3-trimethyl benzene sulfonyl pool Luo) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 ( 4H ) -one (Compound No. 9)

3-amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (112.6 mg, 0.436 mmol) and DMAP (5.9 mg, 0.048 mmol) was dissolved in methylene chloride and anhydrous pyridine (38.7 μL, 0.479 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-trifluoromethylbenzenesulfonyl chloride (76.8 μL, 0.479 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to obtain 50 mg (0.107 mmol, 24.6%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.56 (s, 1H, NH), 10.5 (s, 1H, NH), 8.07-8.01 (m, 3H), 7.83 (t, J = 7.8 Hz, 1H), 7.26 (d, J = 8.8 Hz , 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.86 (t, J = 6.6 Hz, 2H), 3.76 (s, 3H), 2.74 (t, J = 6.6 Hz, 2H)

^{13 C NMR (DMSO, 75 MHz} ): δ 157.8, 141.8, 141.0, 135.3, 134.5, 131.2, 130.3, 129.9, 127.5, 125.7, 123.8, 123.7, 122.0, 116.0, 114.4, 55.7, 52.1, 19.9

Example 10. 3- (3-methoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H ) -One (Compound No. 10)

3-amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (138.1 mg, 0.535 mmol) and DMAP (7.2 mg, 0.059 mmol) was dissolved in methylene chloride and anhydrous pyridine (47.6 μL, 0.589 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-methoxybenzenesulfonyl chloride (83.4 μL, 0.589 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The solid obtained by filtration was washed with methanol and diethyl ether to give 103.1 mg (0.241 mmol, 45%) of the desired compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.48 (s, 1H, NH), 10.21 (s, 1H, NH), 7.48 (t, J = 7.9 Hz, 1H), 7.31-7.18 (m, 5H), 6.95 (d, J = 8.9 Hz , 2H), 3.84 (t, J = 6.7 Hz, 2H), 3.79 (s, 3H), 3.76 (s, 3H), 2.72 (t, J = 6.6 Hz, 2H)

¹³ C NMR (DMSO, 75 MHz): δ 159.6, 157.9, 157.8, 141.9, 141.5, 135.4, 134.3, 130.7, 127.5, 119.2, 118.8, 115.8, 114.4, 112.3, 56.0,

Example 11. 3- (2,5-dimethoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 ( 4H ) -one (Compound No. 11)

3-amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (110.4 mg, 0.427 mmol) and DMAP (5.7 mg, 0.047 mmol) was dissolved in methylene chloride and anhydrous pyridine (37.9 μL, 0.469 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 2,5-dimethoxybenzenesulfonyl chloride (110.9 mg, 0.469 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to obtain 9.8 mg (0.021 mmol, 5%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.43 (s, 1H, NH), 9.88 (s, 1H, NH), 7.25 (d, J = 8.8 Hz, 2H), 7.19-7.16 (m, 3H), 6.94 (d, J = 8.9 Hz , 2H), 3.86-3.80 (m, 5H), 3.75 (s, 3H), 3.71 (s, 3H), 2.71 (br, 2H)

¹³ C NMR (DMSO, 75 MHz):? 157.8, 152.5, 151.0, 127.5, 120.0, 114.9, 114.7, 114.3, 56.9, 56.2, 55.7, 52.0, 20.0.

Example 12. 3- (benzenesulfonyl-2,4-pool Luo) -6- amino-5,6-dihydro-p-methoxy-phenyl -1 H-pyrazolo [3,4- c] pyridin- 7 ( 4H ) -one (Compound No. 12)

3-amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (123.7 mg, 0.479 mmol) and DMAP (6.5 mg, 0.053 mmol) was dissolved in methylene chloride and anhydrous pyridine (42.6 μL, 0.527 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 2,4-difluorobenzenesulfonyl chloride (70.9 μL, 0.527 mmol) was added and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1: 25) to obtain 4.1 mg (0.009 mmol, 2%) of the desired compound as a white solid.

_{^{1 H NMR (CDCl 3, 300MHz}} ): δ 13.70 (s, 1H, NH), 9.28 (s, 1H, NH), 7.77-7.69 (m, 1H), 7.30 (d, J = 8.9 Hz, 2H), 6.97 (d, J = 8.9 Hz , 2H), 6.83 (t, J = 7.3 Hz, 1H), 6.72 (t, J = 8.1 Hz, 1H), 4.00 (t, J = 6.6 Hz, 2H), 3.85 ( s, 3H), 3.10 (t, J = 6.6 Hz, 2H).

¹³ C NMR (CDCl ₃ , 75 MHz):? 158.3, 158.1, 141.2, 135.2, 133.9, 132.2, 126.6, 121.3, 115.3, 114.4, 114.3, 111.4, 105.6, 105.3, 55.5, 52.4, 20.5.

Example 13 3-Benzenesulfonylamino-5,6-dihydro-6- p -methoxyphenyl-1 H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) 13)

3-amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (112.4 mg, 0.435 mmol) and DMAP (5.9 mg, 0.048 mmol) was dissolved in methylene chloride and anhydrous pyridine (38.7 μL, 0.479 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, benzenesulfonyl chloride (61.3 μL, 0.479 mmol) was added and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to obtain 15.2 mg (0.038 mmol, 8.8%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.47 (s, 1H, NH), 10.22 (s, 1H, NH), 7.74 (d, J = 7.0 Hz, 2H), 7.63-7.54 (m, 3H), 7.26 (d, J = 8.8 Hz , 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.84 (t, J = 6.6 Hz, 2H), 3.76 (s, 3H), 2.69 (t, J = 6.6 Hz, 2H)

¹³ C NMR (DMSO, 75 MHz):? 157.9, 157.8, 141.5, 140.7, 135.4, 134.3, 133.1, 129.5, 127.5, 127.2, 115.9, 114.4, 55.8, 52.1, 20.0.

Example 14. 3- (3-benzenesulfonyl pool Luo) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin-7 (4 H ) -one (Compound No. 14)

Amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (112.3 mg, 0.435 mmol) and DMAP ( 5.9 mg, 0.048 mmol) was dissolved in methylene chloride, and anhydrous pyridine (38.7 μL, 0.479 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-fluorobenzenesulfonyl chloride (63.7 μL, 0.479 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to obtain 36.7 mg (0.088 mmol, 20.3%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.53 (s, 1H, NH), 10.39 (s, 1H, NH), 7.68-7.49 (m, 4H), 7.26 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz , 2H), 3.86 (t, J = 6.6 Hz, 2H), 3.76 (s, 3H), 2.74 (t, J = 6.6 Hz, 2H)

¹³ C NMR (DMSO, 75 MHz):? 157.9, 157.8, 141.2, 135.4, 134.4, 132.0, 131.9, 127.6, 123.5, 120.5, 120.2, 116.0, 114.4, 114.0, 55.7,

Example 15 3- (2-Fluorobenzenesulfonyl) amino-5,6-dihydro-6- p -methoxyphenyl-1 H -pyrazolo [3,4- c ] pyridin- H ) -one (Compound No. 15)

3-amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (116.1 mg, 0.449 mmol) and DMAP (6.0 mg, 0.049 mmol) was dissolved in methylene chloride and anhydrous pyridine (40 μL, 0.494 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 2-fluorobenzenesulfonyl chloride (71.4 μL, 0.539 mmol) was added thereto, and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:25) to obtain 121.2 mg (0.291 mmol, 64.8%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.50 (s, 1H, NH), 10.50 (s, 1H, NH), 7.91-7.66 (m, 2H), 7.43 (t, J = 9.4 Hz, 1H), 7.34 (t, J = 7.6 Hz , 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.86 (t, J = 6.6 Hz, 2H), 3.75 ( s, 3H), 2.75 (t, J = 6.6 Hz, 2H)

^{13 C NMR (DMSO, 75 MHz} ): δ 157.9, 157.8, 140.9, 136.0, 135.9, 135.4, 134.3, 130.4, 127.5, 125.2, 117.7, 117.5, 116.1, 114.4, 55.7, 52.1, 19.9

Example 16. 3- (4-benzenesulfonyl pool Luo) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin-7 (4 H ) -one (Compound No. 16)

3-amino-5,6-dihydro-6- (4-methoxyphenyl) -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (204.2 mg, 0.791 mmol) and DMAP (10.6 mg, 0.087 mmol) was dissolved in methylene chloride and anhydrous pyridine (70.4 μL, 0.870 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 4-fluorobenzenesulfonyl chloride (184.7 mg, 0.949 mmol) was added and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:15) to obtain 167.8 mg (0.403 mmol, 50.9%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.50 (s, 1H, NH), 10.28 (s, 1H, NH), 7.79 (dd, J = 5.2, 8.6 Hz, 2H), 7.41 (t, J = 8.8 Hz, 2H), 7.25 (d , J = 8.7 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.85 (br, 2H), 3.76 (s, 3H), 2.72 (br, 2H)

¹³ C NMR (DMSO, 75 MHz):? 166.3, 163.0, 157.8, 137.1, 135.4, 130.3, 130.2, 127.5, 122.3, 116.8, 116.5, 114.4, 55.7, 52.1, 20.0

Example 17 3-Ethylsulfonylamino-5,6-dihydro-6-phenyl-1 H -pyrazolo [3,4- c ] pyridin-7 ( 4H )

3-amino-5,6-dihydro-6-phenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (143 mg, 0.626 mmol) and DMAP (8.3 mg, 0.068 mmol) was dissolved in methylene chloride, and anhydrous pyridine (55.6 μl, 0.688 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, ethanesulfonyl chloride (71 μL, 0.751 mmol) was added and the mixture was stirred at room temperature for 3.5 hours. After extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:20) to obtain 7 mg (0.022 mmol, 3.5%) of the desired compound as a white solid.

_{^{1 H NMR (CDCl 3, 300}} MHz): δ 13.98 (s, 1H, NH), 9.24 (s, 1H, NH), 7.49-7.42 (m, 4H), 7.33-7.29 (m, 1H), 4.07 ( t, J = 6.6 Hz, 2H ), 3.08 (q, J = 7.4 Hz, 2H), 2.90 (t, J = 6.3 Hz, 2H), 1.35 (t, J = 7.4 Hz, 3H)

¹³ C NMR (CDCl ₃ , 75 MHz):? 158.0, 142.5, 141.1, 135.2, 129.3, 129.0, 126.9, 125.2, 119.8, 115.5, 51.9, 46.7, 20.4, 8.0

Example 18; 3- (2,6-dichlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one ( Compound No. 18)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (108 mg, 0.445 mmol) and DMAP (5.9 mg , 0.049 mmol) was dissolved in methylene chloride, and anhydrous pyridine (39.5 μL, 0.489 mmol) was added dropwise at 0 ° C. After 5 minutes, 2,6-dichlorobenzenesulfonyl chloride (131.1 mg, 0.534 mmol) was added and stirred at room temperature for 3.5 hours, followed by heating at 40 ° C overnight. After cooling to room temperature and extraction with methylene chloride, the organic layer was washed with water, dried over anhydrous magnesium sulfate and filtered. The solution was then removed under reduced pressure to obtain 35.8 mg (0.079 mmol, 17.8%) of the desired compound as a white solid.

¹ H NMR (DMSO, 300 MHz): [delta] 13.53 (s, IH, NH), 10.63 (s, IH, NH), 7.63-7.51 (m, 3H), 7.24-7.18 J = 6.5 Hz, 2H), 2.78 (t, J = 6.6 Hz, 2H), 2.30

¹³ C NMR (DMSO, 75 MHz):? 157.8, 140.4, 139.9, 135.8, 135.6, 134.7, 134.2, 134.1, 132.1, 129.6, 126.0, 115.8, 51.8, 21.0,

Example 19. 3- (6-methyl-benzene 2-pool Luo) sulfonyl-amino-5,6-dihydro-6-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 ( 4H ) -one (Compound No. 19)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (113 mg, 0.466 mmol) and DMAP (6.2 mg , 0.051 mmol) was dissolved in methylene chloride, and anhydrous pyridine (41.4 μl, 0.512 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 2-fluoro-6-methylbenzenesulfonyl chloride (116.6 mg, 0.559 mmol) was added and the mixture was stirred at room temperature for 3.5 hours and then heated at 40 ° C overnight. The mixture was cooled to room temperature and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and then the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1:15) to obtain 84.6 mg (0.204 mmol, 43.8%) of the target compound as a white solid.

_{^{1 H NMR (CDCl 3, 300MHz}} ): δ 13.97 (s, 1H, NH), 9.66 (s, 1H, NH), 7.54 (d, J = 5.9 Hz, 1H), 7.37-7.26 (m, 4H), 6.97 (s, 1H), 6.62 (t, J = 8.8 Hz, 1H), 4.01 (br, 2H), 2.86 (br, 2H), 2.40 (s, 3H), 2.18 (s, 3H)

¹³ C NMR (CDCl ₃ , 75 MHz): δ 157.9, 141.0, 138.6, 136.4, 135.2, 135.1, 134.7, 133.9, 133.8, 130.2, 129.4, 125.0, 116.4, 115.2, 51.9, 21.0, 20.4,

Example 20 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (Compound No. 20)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (60 mg, 0.247 mmol) and DMAP (3.3 mg , 0.027 mmol) was dissolved in methylene chloride, and anhydrous pyridine (21.9 μL, 0.271 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-chlorobenzenesulfonyl chloride (41.6 μL, 0.296 mmol) was added and stirred at room temperature for 3.5 hours, followed by heating at 40 ° C. overnight. The reaction mixture was cooled to room temperature and washed with water and diethyl ether to obtain 66.4 mg (0.159 mmol, 64.5%) of the target compound as a white solid.

¹ H NMR (DMSO, 300 MHz):? 13.55 (s, 1H, NH), 10.42 (s, 1H, NH), 7.77-7.58 (m, 4H), 7.24-7.18 2H, J = 6.5 Hz, 2H), 2.75 (t, J =

^{13 C NMR (DMSO, 75 MHz} ): δ 157.8, 142.5, 141.1, 140.0, 135.8, 134.4, 134.0, 133.1, 131.6, 129.6, 126.7, 126.0, 125.9, 116.0, 51.8, 21.0, 20.0

Example 21. 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin-7 (4 H ) -one (Compound No. 21)

3-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (113 mg, 0.466 mmol) and DMAP (6.2 mg , 0.051 mmol) was dissolved in methylene chloride, and anhydrous pyridine (41.4 μL, 0.512 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-chloro-2-methylbenzenesulfonyl chloride (125.8 mg, 0.559 mmol) was added and stirred at room temperature for 3.5 hours and then heated at 40 ° C overnight. The mixture was cooled to room temperature and washed with water and diethyl ether to obtain 82.4 mg (0.191 mmol, 41.0%) of the target compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.55 (s, 1H, NH), 10.51 (s, 1H, NH), 7.83 (d, J = 7.8 Hz, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.20 (s, 4H), 3.87 (t, J = 6.5 Hz, 2H), 2.73 (br, 2H), 2.63 (s, 3H), 2.30 ( s, 3H)

¹³ C NMR (DMSO, 75 MHz):? 141.2, 140.0, 136.1, 135.8, 134.8, 133.9, 129.6, 128.4, 127.8, 126.0, 116.0, 51.8, 21.0, 19.9, 17.0

Example 22. 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-benzyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -One (Compound No. 22)

3-Amino-6-benzyl-5,6-dihydro -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (112 mg, 0.462 mmol) and DMAP (6.2 mg, 0.051 mmol) was dissolved in methylene chloride, and anhydrous pyridine (41.1 μL, 0.508 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-chloro-2-methylbenzenesulfonyl chloride (124.7 mg, 0.554 mmol) was added and the mixture was stirred at room temperature for 3.5 hours and heated at 40 ° C overnight. The reaction mixture was cooled to room temperature, and washed with water and diethyl ether to obtain 173.9 mg (0.403 mmol, 87.3%) of the title compound as a white solid.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.48 (s, 1H, NH), 10.41 (s, 1H, NH), 7.80 (d, J = 7.8 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.38-7.25 (m, 6H ), 4.60 (s, 2H), 3.42 (t, J = 6.4 Hz, 2H), 2.59 (s, 3H), 2.57 (br, 2H)

^{13 C NMR (DMSO, 75 MHz} ): δ 158.4, 141.2, 137.8, 136.5, 136.1, 134.8, 133.9, 129.0, 128.4, 128.0, 127.7, 127.6, 115.6, 48.9, 47.8, 19.3, 17.0

Example 23. 3- (3-Chlorobenzene) sulfonylamino-5,6-dihydro-6-benzyl-1 H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) No. 23)

3-Amino-6-benzyl-5,6-dihydro -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (116 mg, 0.478 mmol) and DMAP (6.35 mg, 0.052 mmol) was dissolved in methylene chloride, and anhydrous pyridine (42.4 μL, 0.525 mmol) was added dropwise at 0 ° C. After stirring for 5 minutes, 3-chlorobenzenesulfonyl chloride (80.6 μL, 0.573 mmol) was added and stirred at room temperature for 3.5 hours, followed by heating at 40 ° C. overnight. The reaction mixture was cooled to room temperature and washed with water and diethyl ether to give 157.5 mg (0.377 mmol, 79.1%) of the title compound as a white solid.

¹ H NMR (DMSO, 300 MHz): [delta] 13.51 (s, 1H, NH), 10.36 (s, 1H, NH), 7.73-7.56 (m, 4H), 7.36-7.26 , 2H), 3.43 (t, J = 6.6 Hz, 2H), 2.56 (t, J = 6.7 Hz, 2H).

¹³ C NMR (DMSO, 75 MHz):? 158.2, 142.5, 141.1, 137.8, 134.0, 134.0, 133.1, 131.6, 129.0, 128.0, 127.7, 126.7, 125.9, 115.5, 48.8, 47.8, 19.4.

Example 24. 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - One (Compound No. 24)

3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro -6- (N-tert- butoxycarbonyl) piperidinyl-methyl -1 H-pyrazolo [3,4- c] pyridin- 7 ( 4H ) -one (183.3 mg, 0.349 mmol) in anhydrous methylene chloride (0.43 mL) was cooled to 0 C and an equal volume of 50% TFA was added. The solution was stirred at room temperature overnight, then the reaction mixture was concentrated and suspended in ethyl acetate. The solution was transferred to a separatory funnel and washed with saturated NaHCO ₃ (3.4 mL) solution until clear solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 x 5 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and the solution was removed under reduced pressure. The product was further purified by column chromatography (MeOH / CH ₂ Cl ₂ , 1: 3) to obtain 23.8 mg (0.044 mmol, 12.6%) of the hydrochloride of the target compound as a white solid.

_{^{1 H NMR (CD 3 OD,}} 300 MHz): δ 7.73 (s, 1H), 7.69 (d, J = 7.5 Hz, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 3.53 ( t, J = 6.7 Hz, 2H), 3.45-3.38 (m, 4H), 2.98 (td, J = 2.6,12.6 Hz, 2H), 2.56 (t, J = 6.5 Hz, 2H), 2.03 (d, J = 7.0 Hz, 1H), 1.90 (d, J =

¹³ C NMR (CD ₃ OD, 75 MHz):? 141.5, 134.0, 130.9, 130.0, 126.2, 124.6, 50.3, 43.4, 32.5, 29.3, 26.3, 19.1

Example 25. 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin-7 ( 4H ) -one (Compound No. 25)

3-Chlorobenzene) sulfonylamino-5,6-dihydro-6- ( N - tert -butoxycarbonyl) piperidinylmethyl-1 H- pyrazolo [3,4- c ] pyridin-7 ( 4H ) -one (219.5 mg, 0.408 mmol) in anhydrous methylene chloride (0.51 mL) was cooled to 0 ° C and an equal volume of 50% TFA was added. The solution was stirred at room temperature for 30 minutes. The methylene chloride was removed and the residue was purified by column chromatography to obtain 217.2 mg (0.393 mmol, 96.5%) of the hydrochloride of the desired compound.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.39 (s, 1H, NH), 10.42 (s, 1H), 8.57 (s, 1H, NH), 8.27 (s, 1H, NH), 7.81 (d, J = 7.8 Hz, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.36 (t, J = 7.9 Hz, 1H), 3.47 (t, J = 8.4 Hz, 2H), 3.29 (d, J = 7.8 Hz, 2H), 3.16 (d , J = 3.6 Hz, 2H), 2.81 (t, J = 11.6 Hz, 2H), 2.59 (s, 5H), 1.90 (br, 1H), 1.72 (d, J = 12.7 Hz, 2H), 1.30 (q, J = 11.5 Hz, 2H)

^{13 C NMR (DMSO, 75 MHz} ): δ 158.6, 158.3, 158.2, 141.3, 136.0, 134.8, 133.8, 128.3, 127.7, 115.6, 50.2, 49.0, 48.5, 43.4, 32.4, 26.5, 19.5, 17.0

Example 26. 3- (1-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (Compound No. 26)

Preparation of 3- (1-naphthalene) sulfonylamino-5,6-dihydro-6- ( N - tert -butoxycarbonyl) piperidinylmethyl-1 H -pyrazolo [3,4- c ] ( 4H ) -one (137.2 mg, 0.254 mmol) was dissolved in ethyl acetate, and hydrochloric acid gas was blown at room temperature. Upon completion of the reaction by TLC, filtration afforded 68.2 mg (0.143 mmol, 56.4%) of the hydrochloride of the desired compound.

^{1 H NMR (DMSO, 300 MHz} ): δ 10.46 (s, 1H), 8.95 (br, 1H, NH), 8.68 (br, 1H, NH), 8.59 (d, J = 9.6 Hz, 1H), 8.21 ( d, J = 8.2 Hz, 1H ), 8.22-8.06 (m, 2H), 7.69-7.57 (m, 3H), 3.34 (t, J = 6.1 Hz, 2H), 3.26-3.19 (m, 4H), 2.77 (q, J = 9.8 Hz, 2H), 2.36 (t, J = 6.2 Hz, 2H), 1.86 (br, 1H), 1.67 (d, J = 13.2 Hz, 2H), 1.32 (q, J = 11.3 Hz , 2H)

¹³ C NMR (DMSO, 75 MHz):? 158.5, 140.2, 136.0, 134.5, 134.2, 129.3, 128.2, 127.2, 125.1, 124.9, 115.3, 50.1, 48.3, 43.1, 32.5, 26.4, 19.4.

Example 27. 3- (2-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one (Compound No. 27)

3- (2-naphthalene) sulfonyl-amino-5,6-dihydro -6- (N - tert- butoxycarbonyl) piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H ) -one (131.5 mg, 0.243 mmol) was dissolved in ethyl acetate, and hydrochloric acid gas was blown at room temperature. Upon completion of the reaction by TLC, filtration yielded 90.2 mg (0.189 mmol, 78%) of the hydrochloride of the desired compound.

^{1 H NMR (DMSO, 300 MHz} ): δ 10.30 (s, 1H), 8.96 (br, 1H, NH), 8.72 (br, 1H, NH), 8.32 (s, 1H), 8.10 d, J = 8.7 Hz , 2H), 8.02 (d, J = 7.9 Hz, 1H), 7.77 (dd, J = 1.7,8.6 Hz, 1H), 7.72-7.62 (m, 2H), 3.43 (t, J = 6.7 Hz, 2H) , 3.28-3.19 (m, 4H), 2.77 (q, J = 9.9 Hz, 2H), 2.52 (t, J = 6.5 Hz, 2H), 1.87 (br, 1H), 1.69 (d, J = 12.4 Hz, 2H), 1.34 (q, J = 11.4 Hz, 2H)

^{13 C NMR (DMSO, 75 MHz} ): δ 158.6, 140.5, 137.8, 134.6, 132.0, 129.6, 129.5, 129.3, 128.2, 128.0, 122.9, 115.4, 50.2, 48.4, 43.1, 32.5, 26.4, 19.5

Example 28. 3- (2-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one ( Compound No. 28)

3- (2-naphthalene) sulfonyl-amino-5,6-dihydro -6- (N - tert- butoxycarbonyl) piperidinyl -1 H - pyrazolo [3,4- c] pyridin-7 ( 4H ) -one (148.8 mg, 0.283 mmol) was dissolved in ethyl acetate, and hydrochloric acid gas was blown at room temperature. Upon completion of the reaction by TLC, filtration yielded 97.9 mg (0.211 mmol, 74.9%) of the desired compound hydrochloride.

^{1 H NMR (DMSO, 300 MHz} ): δ 10.32 (s, 1H), 8.82 (br, 1H, NH), 8.74 (br, 1H, NH), 8.32 (s, 1H), 8.10 (d, J = 8.4 Hz, 2H), 8.02 (d , J = 7.9 Hz, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.72-7.61 (m, 2H), 4.57 (t, J = 12.0 Hz, 1H), 3.34-3.30 (m, 4H), 3.00 (q, J = 11.0 Hz, 2H), 2.54 (t, J = 6.2 Hz, 2H), 1.96 (q, J = 11.9 Hz, 2H), 1.67 (d, J = 11.7 Hz, 2H)

^{13 C NMR (DMSO, 75 MHz} ): δ 158.2, 140.5, 137.8, 134.9, 134.7, 132.0, 129.6, 129.5, 129.3, 128.2, 128.0, 128.0, 122.9, 115.3, 47.3, 43.2, 42.5, 25.8, 19.8

Example 29. 3- (4- tert- butyl-benzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H ) -One (Compound No. 29)

3- (4- tert- butyl-benzene) sulfonyl-amino-5,6-dihydro -6- (N - tert- butoxycarbonyl) piperidinyl-methyl -1 H - pyrazolo [3,4- c] Pyridin-7 ( 4H ) -one (175.5 mg, 0.321 mmol) was dissolved in ethyl acetate, and hydrochloric acid gas was blown at room temperature. When the reaction was completed by confirming with TLC, filtration yielded 111.8 mg (0.231 mmol, 72.2%) of the desired compound hydrochloride.

^{1 H NMR (DMSO, 300 MHz} ): δ 10.11 (s, 1H), 8.91 (br, 1H, NH), 8.67 (br, 1H, NH), 7.64-7.55 (m, 4H), 3.43 (t, J = 6.4 Hz, 2H), 3.28 (d, J = 7.1 Hz, 2H), 3.22 (d, J = 12.5 Hz, 2H), 2.78 (q, J = 10.7 Hz, 2H), 2.45 (br, 2H), (D, J = 13.0 Hz, 2H), 1.35 (q, J = 12.2 Hz, 2H), 1.28

¹³ C NMR (DMSO, 75 MHz):? 158.7, 156.2, 137.9, 127.0, 126.3, 115.2, 50.2, 48.5, 43.2, 35.3, 32.5, 31.2, 26.5, 19.5

Example 30. 3- (5-methyl-benzene 2-pool Luo) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H-pyrazolo [3,4- c] pyridin- 7 ( 4H ) -one (Compound No. 30)

Preparation of 3- (2 - fluoro-5-methylbenzenesulfonylamino) -5,6-dihydro-6- ( N - tert -butoxycarbonyl) piperidinylmethyl-1 H- pyrazolo [ C ] pyridin-7 ( 4H ) -one (166.3 mg, 0.318 mmol) was dissolved in ethyl acetate, and hydrochloric acid gas was blown at room temperature. After completion of the reaction, the reaction mixture was filtered. The filtrate was purified by column chromatography (MeOH: CH ₂ Cl ₂ , 1: 1) to obtain 101.4 mg (0.221 mmol, 69.6%) of the target compound hydrochloride.

^{1 H NMR (DMSO, 300 MHz} ): δ 10.37 (s, 1H), 9.08 (br, 1H, NH), 8.83 (br, 1H, NH), 7.52 (d, J = 6.7 Hz, 1H), 7.48- 7.45 (m, 1H), 7.28 (t, J = 9.2 Hz, 1H), 3.48 (t, J = 6.6 Hz, 2H), 3.29 (d, J = 6.9 Hz, 2H), 3.21 (d, J = 12.3 Hz, 2H), 2.78 (q , J = 10.4 Hz, 2H), 2.59 (t, J = 6.1 Hz, 2H), 2.29 (s, 3H), 1.90 (br, 1H), 1.71 (d, J = 12.9 Hz, 2H), 1.38 (q, J = 11.2 Hz, 2H)

^{13 C NMR (DMSO, 75 MHz} ): δ 158.6, 155.2, 135.2, 136.1, 134.5, 134.5, 130.0, 128.1, 127.9, 117.5, 117.2, 115.5, 50.2, 48.5, 43.1, 32.5, 26.5, 20.4, 19.4

Example 31. 3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -One (Compound No. 31)

3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro -6- (N - tert- butoxycarbonyl) piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridine -7 ( 4H ) -one (160.9 mg, 0.309 mmol) was dissolved in methylene chloride and methanol, and hydrochloric acid gas was blown at room temperature. Upon completion of the reaction by TLC, filtration afforded 117.7 mg (0.258 mmol, 83.6%) of the desired compound hydrochloride.

^{1 H NMR (DMSO, 300 MHz} ): δ 13.31 (s, 1H, NH), 10.02 (s, 1H), 8.96 (br, 1H, NH), 8.70 (br, 1H, NH), 7.62 (d, J = 9.3 Hz, 2H), 7.06 (d, J = 10.3 Hz, 2H), 3.81 (s, 3H), 3.46 (t, J = 6.2 Hz, 2H), 3.29 (d, J = 7.2 Hz, 2H), 3.22 (d, J = 12.4 Hz , 2H), 2.79 (q, J = 10.5 Hz, 2H), 2.53 (br, 2H), 1.90 (br, 1H), 1.72 (d, J = 12.7 Hz, 2H), 1.36 (q, J = 11.3 Hz, 2H)

¹³ C NMR (DMSO, 75 MHz): δ 162.8, 158.6, 132.3, 129.3, 115.2, 114.6, 56.1, 50.2, 48.5, 43.2, 32.5, 26.5, 19.5

Example 32. 3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - One (Compound No. 32)

3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro -6- (N-tert- butoxycarbonyl) piperidinyl -1 H-pyrazolo [3,4- c] pyridin- 7 ( 4H ) -one (140 mg, 0.276 mmol) was dissolved in ethyl acetate, and hydrochloric acid gas was blown at room temperature. Upon completion of the reaction by TLC, the reaction mixture was filtered to obtain 108 mg (0.244 mmol, 88.6%) of hydrochloride of the desired compound as a clear yellow compound.

^{1 H NMR (DMSO, 300 MHz} ): δ 10.05 (s, 1H), 9.10 (s, 1H, NH), 9.04 (s, 1H, NH), 7.62 (d, J = 8.8 Hz, 2H), 7.05 ( d, J = 8.9 Hz, 2H ), 4.63-4.55 (m, 1H), 3.80 (s, 3H), 3.35 (t, J = 6.6 Hz, 2H), 3.31 (d, J = 12.8 Hz, 2H), 2.99 (q, J = 9.9 Hz , 2H), 2.51 (t, J = 6.7 Hz, 2H), 2.04 (qd, J = 2.4, 11.9 Hz, 2H), 1.67 (d, J = 11.8 Hz, 2H)

¹³ C NMR (DMSO, 75 MHz):? 162.8, 158.2, 140.6, 135.0, 132.3, 129.3, 115.0, 114.6, 56.1, 47.3, 43.2, 42.5, 25.8, 19.8

[Experimental Example]

Experimental example. Experiments on accumulation of cyclic adenosine monophosphate

In order to confirm the inhibitory activity against the 5-HT ₆ receptor of the compound represented by the above formula (1), an experiment for analyzing the accumulation amount of cyclic adenosine monophosphate (c-AMP) Respectively.

The cAMP dynamic 2 kit (CIS bio international, France) was used to measure the amount of cAMP in the cells in response to extracellular factors.

3 mL of cell separation buffer was added to HEK293 cell line expressing the human 5-HT ₆ receptor cultured in a 100 mm dish, and then cells were separated using a centrifuge. 3-isobutyl-1-methylxanthine (IBMX), which inhibits the activity of phosphodiesterase, an enzyme that catalyzes the degradation of cAMP, into isolated cells, agonist drugs and antagonist drugs And diluted in phosphate-buffered saline (PBS). Diluted cells were diluted to a final concentration of 8x10 ² cells / μL using a hematocytometer. 5 μL of cells diluted in 384 wells were pre-treated with 2.5 μL of the inhibitory drug (final concentration 10 μM) in a 5% CO ₂ incubator at 37 ° C. for 10 minutes. After 10 minutes, 2.5 μL of the inhibitory drug (final concentration 10 μM) was added and the cells were treated sufficiently for 30 minutes at 37 ° C. in a 5% CO ₂ incubator in an amount sufficient to measure cAMP. After 30 minutes of treatment, cAMP-d2 bound to cAMP and staining agent and anti-cAMP cryptate conjugate, which binds to cAMP accumulated in the cells, was diluted 1: 4 in lysis buffer (cAMP-d2: lysis buffer = 1: 4, Anti-cAMP Cryptate conjugate: lysis buffer = 1: 4). First, 5 μL of diluted cAMP-d2 was added, followed by 5 μL of diluted anti-cAMP Cryptate conjugate. After reacting at room temperature for 1 hour, the amount of cAMP was measured using Flex-3 (Molecular Devices, USA) through TR-FRET (time-resolved fluorescence resonance transfer) value. The amount of cAMP was calculated from the fluorescence values of 620 nm and 665 nm emitted at a wavelength of 337 nm. The inhibitory activity against the 5-HT ₆ receptor was calculated based on the amount of cAMP measured. Table 1 below shows the percent inhibition and IC ₅₀ values for the 5-HT ₆ receptor.

Experimental compound Molecular Weight % Inhibition rate
(at 10 [mu] M) IC ₅₀
(at 10 [mu] M) Compound No. 1 382.44 23.5 ± 12.2 Compound No. 2 400.43 18.1 ± 6.9 Compound No. 3 450.43 69.0 ± 4.3 3.28 ± 0.83 Compound No. 4 412.46 61.8 + - 8.3 6.77 ± 1.29 Compound No. 5 442.49 3.8 ± 3.6 Compound No. 7 400.43 29.6 ± 10.6 Compound No. 8 400.43 79.3 ± 1.6 5.22 ± 0.76 Compound No. 10 428.46 63.3 ± 3.2 7.08 ± 0.8 Compound No. 11 458.49 19.6 ± 4.1 Compound No. 12 320.37 20.9 ± 6.0 Compound No. 13 398.44 30.6 ± 9.2 Compound No. 14 416.43 95.2 ± 7.0 0.58 ± 0.15 Compound No. 15 416.43 19.3 ± 2.8 Compound No. 17 320.37 13.8 ± 7.1 Compound No. 18 451.33 68.4 ± 6.9 5.48 ± 0.99 Compound No. 19 414.45 25.9 ± 11.8 Compound No. 20 416.88 5.4 ± 5.1 Compound No. 21 430.91 92.2 ± 8.8 0.68 ± 0.10 Compound No. 22 430.91 77.9 ± 3.7 3.28 ± 0.83 Compound No. 24 537.94 31.0 ± 13.9 Compound No. 25 551.96 51.7 ± 9.7 Compound No. 26 475.99 40.9 ± 6.8 Compound No. 27 475.99 94.1 ± 3.0 0.31 0.10 Compound No. 28 461.96 89.5 ± 7.7 0.77 ± 0.09 Compound No. 29 482.04 11.5 ± 5.1 Compound No. 30 457.95 30.6 ± 4.8 Compound No. 31 455.96 15.1 ± 6.4 Compound No. 32 441.93 26.1 ± 6.9 Control drug
(SB258585) 99.7 ± 1.9 0.019 ± .5

As shown in Table 1, it was confirmed that the compound of the present invention has an inhibitory activity on the serotonin 5-HT ₆ receptor when treated with HELA cells expressing 5-HT ₆ receptors stably . That is, it has been confirmed that the compound according to the present invention can be used as an early diagnosis reagent as well as a preventive and therapeutic agent for central nervous system diseases caused by serotonin 5-HT ₆ activity. Compared to SB258585, which is currently being developed by Glaxo Smith Kline, which is well known in this field, the compounds of the present invention have almost similar activity.

Experimental Example 2: Toxicity test

In order to examine the toxicity of the compound represented by the formula (1), in the present experimental example, 1 to 20 mg of the active substance was intraperitoneally administered to 24 mice, and survival was confirmed for 24 hours after the observation.

As a result, the compounds of the present invention had no concern about toxicity. Three out of six mice administered 20 ㎎ survived and the remaining three were sacrificed. On the other hand, mice with a dose of less than 20 mg survived, and no statistically significant difference was observed compared to mice that did not receive the drug. Taking the above results into account, the compounds of the present invention are judged to have a toxic dose (TD ₅₀ ) of about 20 mg (1 mg / g) in which roughly half of mice can survive.

[Formulation Example]

Formulation Example 1: Preparation of tablets

In this Example, tablets for oral administration were prepared by the wet granulation method and the dry granulation method using the compound represented by Formula 1 as an active ingredient in the following composition.

[Furtherance]

200 mg of active ingredient, 10 mg of light silicic anhydride, 2 mg of magnesium stearate, 50 mg of microcrystalline cellulose, 25 mg of starch glycolic acid sodium, 113 mg of corn starch, and anhydrous ethanol.

Formulation Example 2: Preparation of injection

In this Example, an injection was prepared using the compound represented by Formula 1 as an active ingredient with the following composition.

[Furtherance]

100 mg of active ingredient, 180 mg of mannitol, 25 mg of sodium monohydrogenphosphate, 2974 mg of water for injection

As described above, the compound represented by Formula 1 is excellent in the inhibition and binding activity to 5-HT ₆ receptor, and thus is useful for diagnosis, prevention and treatment of CNS diseases caused by 5-HT ₆ activity .

Accordingly, the composition containing the compound represented by Formula 1 as an active ingredient according to the present invention is useful as a therapeutic agent for central nervous system diseases caused by 5-HT ₆ activity, such as Alzheimer's disease (AD), attention deficit disorder (ADHD) , Depression, obesity, schizophrenia, sleep disorders, pain anxiety, and the like.

Claims (11)

5-sulfonylamino-5,6-dihydro- 1H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) -one compound represented by the following formula 1 and a pharmaceutically acceptable salt thereof Selected from the group consisting of:
[Chemical Formula 1]

In Formula 1,
R ₁ is a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl, or substituted or unsubstituted piperidinyl Lt; / RTI >
R ₂ is a hydrogen atom, a C _{1 to} C ₆ alkyl group, a naphthalenyl group, or a substituted alkyl group having 1 to 3 substituents selected from halo, C _{1 to} C ₆ alkyl, C _{1 to} C ₆ alkoxy, and C _{1 to} C ₆ haloalkyl A substituted or unsubstituted phenyl group,
n represents an integer of 0 to 6;
The method according to claim 1,
Wherein R ₁ represents a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkoxycarbonyl,
R ₂ represents a C ₁ -C ₆ alkyl group,
Wherein n is 0.
The method according to claim 1,
Wherein R ₁ represents a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkoxycarbonyl,
R ₂ represents a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl,
Wherein n is 0.
The method according to claim 1,
Wherein R ₁ represents a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy and C ₁ -C ₆ alkoxycarbonyl,
R ₂ represents a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl,
Wherein n is 1.
The method according to claim 1,
Wherein R ₁ represents a piperidinyl group substituted or unsubstituted with a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl,
R ₂ represents a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl,
Wherein n is 0.
The method according to claim 1,
Wherein R ₁ represents a piperidinyl group substituted or unsubstituted with a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl,
R ₂ represents a phenyl group substituted or unsubstituted with 1 to 3 substituents selected from halo, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ haloalkyl,
Wherein n is 1.
The method according to claim 1,
Wherein R ₁ represents a piperidinyl group substituted or unsubstituted with a substituent selected from C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, and C ₁ -C ₆ alkoxycarbonyl,
R ₂ represents a naphthalenyl group,
Wherein n is 1.
The method according to claim 1,
Compound No. 1; 3-benzenesulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 2; 3- (3-benzene pool Luo) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 3; 3- (3-triethoxysilylpropyl pool Luo methyl benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 4; 3- (3-methoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 5; 3- (2,5-dimethoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 6; 3- (2,4-benzenesulfonyl a full Luo) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - On
Compound No. 7; 3- (2-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 8; 3- (4-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 9; 3- (3-trimethyl benzene sulfonyl pool Luo) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -On
Compound No. 10; Dihydro-6- p -methoxyphenyl-1 H -pyrazolo [3,4- c ] pyridin-7 ( 4H ) -one
Compound No. 11; 3- (2,5-dimethoxy-benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -On
Compound No. 12; 3- (2,4-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H )-On
Compound No. 13; 3-benzenesulfonylamino-5,6-dihydro-6- p -methoxyphenyl-1 H -pyrazolo [3,4- c ] pyridin-7 ( 4H )
Compound No. 14; 3- (3-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 15; 3- (2-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 16; 3- (4-pool Luo benzenesulfonyl) -6- amino-5,6-dihydro-p - methoxyphenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 17; 3-ethyl-sulfonylamino-5,6-dihydro-6-phenyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 18; 3- (2,6-dichlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 19; 3- (6-methyl-benzene 2-pool Luo) sulfonyl-amino-5,6-dihydro-6-p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) -On
Compound No. 20; 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 21; 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro -6- p - tolyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 22; 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-benzyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 23; 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-benzyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 24; 3- (3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 25; 3- (2-methyl-3-chlorobenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - On
Compound No. 26; 3- (1-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 27; 3- (2-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 28; 3- (2-naphthalene) sulfonyl-amino-5,6-dihydro-6-piperidinyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 29; 3- (4- tert- butyl-benzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 30; 3- (5-methyl-benzene 2-pool Luo) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H )-On
Compound No. 31; 3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl-methyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
Compound No. 32; 3- (4-methoxybenzene) sulfonyl-amino-5,6-dihydro-6-piperidinyl -1 H - pyrazolo [3,4- c] pyridin -7 (4 H) - one
≪ / RTI >
The method according to claim 1,
Lt; RTI ID = 0.0 > pharmaceutically < / RTI > acceptable salt is an acid addition salt.
10. A pharmaceutical composition comprising a compound of any one of claims 1 to 9 as an active ingredient and selected from the group consisting of Alzheimer's (AD), Attention Deficit Hyperactivity Disorder (ADHD), epilepsy, depression, obesity, schizophrenia, (CNS) disease selected from the group consisting of: < RTI ID = 0.0 >
9. A pharmaceutical composition for the treatment or prophylaxis of Alzheimer's (AD), Attention Deficit Hyperactivity Disorder (ADHD), epilepsy, depression, obesity, schizophrenia, sleep disturbance and pain anxiety disorder characterized by comprising a compound of any one of claims 1 to 9 Diagnostic reagents for selected central nervous system (CNS) diseases.