KR20100097077A - Pyridinone derivertives having inhibition activity on hsp90 - Google Patents

Abstract

PURPOSE: A novel compound with efficiency of suppressing HSP90(heat shock protein) is provided to treat various diseases associated to HSP90 activation. CONSTITUTION: A pharmaceutical composition for treating HSP90 activation-associated diseases contains a compound of chemical formula 1, pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof. A method for preparing a compound of chemical formula 2 comprises: a step of reacting a compound of chemical formula 4 with a compound of chemical formula 3 to obtain a compound of chemical formula 5; and a step of hydrolyzing nitrile group(CN) of the compound of chemical formula 5. The compound of chemical formula 3 is obtained by reacting a compound of chemical formula 7 with a compound of chemical formula 6 under the presence of base.

Description

Pyridinone derivative having inhibitory effect against HSP90 {PYRIDINONE DERIVERTIVES HAVING INHIBITION ACTIVITY ON HSP90}

The present invention relates to a novel compound derivative having a pyridinone skeleton that inhibits the activity of the Heat shock 90 protein, a preparation method thereof, and a pharmaceutical composition containing the same.

Over the years, molecular targeted therapies have been the focus of anti-cancer drug development programs. For example, as seen in the case of imatinib (gleevec), this therapy has proven to be very successful if the cancer is dependent on the target oncoprotein. However, most cancers are characterized by multiple molecular mutations. Thus, targeting only one molecular variation may be insufficient and it is possible that only a subset of tumors in which the targeting protein plays a key role will have a significant effect. One strategy to overcome this problem is to target the machinery that makes cancer cells work. HSP90, a molecular chaperone, is a key component of this mechanism, which is necessary for the function of various mutagenic or overexpressing signaling proteins that promote the growth and survival of cancer cells. This means that HSP90 inhibitors can be effective against a wide variety of cancers.

Heat shock 90 protein (HSP90) is one of the most abundant chaperones in cells. It is known to exist as 1-2% of the total protein in normal cells and 4-6% when stress is present. HSP70, known as an important chaperone with HSP90, aids in the folding process by binding to the hydrophobic portion of the newly produced polypeptide chain in ribosomes, while HSP90 is in a stable state with partial folding by HSP70. It has been reported to play a role in binding to proteins to complete folding (Csermely, P., Schnaider, T., Soti, C., Prohaszka, Z., and Nardai, G. (1998) Pharmacol Ther 79 (2) , 129-168). In the cytoplasm of eukaryotes, two types of HSP90a and HSP90b exist as isoforms. Structurally, a 25-kDa N-terminal ATPase binding moiety, a "charged linker" N-terminal and a middle domain Can be divided into a linking site, a middle domain of about 40 kDa, and a C-terminal domain of about ~ 12 kDa (Pearl, LH, and Prodromou, C. (2006) Annu Rev Biochem, 75. 271 -294). The middle domain is known to be involved in the binding of client proteins and is involved in the folding of many client proteins and in particular the structural maturation of oncogenic signaling proteins. Recently, it is emerging as a target of various anticancer drugs. The interaction of HSP90 with client proteins is via complex and cyclic hydrolysis of ATP. HSP90 has not been reported to be involved in the biosynthesis process of most polypeptides (Freeman BC, Yamamoto Kr. Science 2002 June 21; 296 (5576): 2232-2235).

Client proteins of HSP90 are known to be the major proteins involved in intracellular signaling, including steroid hormone receptors, transcriptional regulators, kinases, and cell cycle regulators, but the list of HSP90 client proteins continues to grow. Using HSP90 chaperone network at the dielectric level was investigated. The results revealed that HSP90 modulates various cellular functions by identifying physical and chemical interactions between HSP90 and about 200 proteins and genetic and chemical interactions with about 450 proteins and HSP90.

The sequential change in structure by binding to the HSP90 N-terminal ATPase domain and dissociation of HSP70 acts as an essential element for the activity of HSP90 by regulating the binding of substrate and co-chaperone.

Protein folding by HSP90 is a highly dynamic process involving the binding and separation of HSP70 and various co-chaperones, and most studies have been conducted on the folding of steroid hormone receptors.

Cancer development is accompanied by infinite cell division and metastasis to surrounding cells due to abnormal cell growth regulation. Therefore, the six characteristics that appear in cancer include cell proliferation through self-growth signal, decreased responsiveness to growth suppression signal, avoidance of apoptosis process, acquisition of infinite proliferation capacity, continuous vascular proliferation, cell infiltration and metastasis. . Many client proteins whose stability and activity are regulated by HSP90 are involved in the differentiation of these cancer cells. In addition, HSP90 is known to induce the evolution of organisms by protecting proteins in unstable state. Unstable mutant proteins such as V-src, Bcr-Abl, and p53 generated during transformation are stabilized by HSP90 to promote differentiation into cancer cells. Cause results.

On the other hand, since the expression and activity of HSP90 is observed in cancer cells, development of drugs that inhibit HSP90 may be essential for the development of anticancer drugs that can selectively act only on cancer cells. In addition, since HSP90 inhibitors destabilize a variety of cancer-causing factors, compared to existing anticancer drugs that act on specific targets, there is a possibility that they can be developed as therapeutic agents for various cancers. For example, HER2, RAF, KIT, MET, which are involved in promoting self-growth, and CDK4, CDK6, Cyclin D, which regulate the reactivity of growth inhibition signals, and IGF-IR, AKT, and infinite, which induce evasion from the process of cell death. Htert involved in proliferative capacity, HIF, MET, Src, VEGF, which causes continuous vascular proliferation, Met and MMP2, which are involved in cancer cell metastasis, are the representative client proteins stabilized by HSP90. HSP90 inhibitors destabilize their Induces anti-cancer effects. Moreover, since HSP90 is not only specifically activated in tumor cells but also exists in a high affinity form, HSP90 inhibitors have the advantage of showing high selectivity for tumor cells.

Disclosure of Invention The present invention aims to provide a novel compound having a therapeutically effective effect of inhibiting the activity of Heat shock protein 90 (HSP90), a preparation method thereof, and a pharmaceutical composition comprising the same under the above technical background.

The present invention

Provided are novel compounds represented by Formula 1, pharmaceutically acceptable salts, hydrates, solvates or isomers thereof:

Where

D is C or N,

R1 is hydrogen, halogen, CN, NO ₂ , guanidino, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, trihalo (C1-C4) Alkoxy, trihalo (C 1 -C 4) alkyl,-(CH ₂ ) _0-6 -R ^a , -C2-C6 alkenyl-R ^a ,-(CH ₂ ) _0-6 -OR ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) R ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) OR ^a ,-(CH ₂ ) _{0 ~ 6} -S (O) R ^a ,-(CH ₂ ) _{0 6-} SO ₂ R ^a , -OC (O) R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , -NHC (O) R ^a , -C (O) NR ^a R ^b , -NHC (S) R ^a , -C (S) NR ^a R ^b , -SR ^a , -NHSO ₂ R ^a , -SO ₂ NR ^a R ^b , -OSO ₂ R ^a , or -SO ₂ OR ^a , wherein R ^a and R ^b are each independently hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, COOH Substituted with one or more substituents selected from the group consisting of: -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Unsubstituted C1-C8 alkyl;

,

및

기로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환 또는 비치환된 C3-C8 시클로알킬 또는 C3-C8 헤테로시클로알킬; 또는 C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C3-C8 cycloalkyl or C3-C8 heterocycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of groups; or

,

및

기로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환 또는 비치환된 C6~C18 아릴 또는 C3~C18 헤테로아릴기이며;C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with one or more substituents selected from the group consisting of groups;

Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;

R2 is hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2- C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, (C1-C4) alkyl substituted with C3-C8 heterocycloalkyl group, trihalo ( C 1 -C 4) alkoxy, trihalo (C 1 -C 4) alkyl, C 1 -C 4 dialkylamino, amines substituted by straight or branched C 1 -C 8 alkyl groups, amines substituted by C 3 -C 8 cycloalkyl groups, C 1 -C 6 Alkylamino (C1-C4) alkyl, C1-C6 dialkylamino (C1-C8) alkyl, C1-C6 alkyleneimino (C1-C4) alkyl group, or-(CH ₂ ) _0-6 -NR ^a , Where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C3-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, One or more substituents selected from the group consisting of -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl A substituted or unsubstituted C6-C18 aryl or C3-C18 heteroaryl group;

R3 is hydrogen; halogen; CN; NO ₂ ; OH; -SH; -COOH; Formyl; Guanidino; -CONH ₂ ; Straight or branched C1-C8 alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C1-C8 alkoxy; Straight or branched C1-C8 alkyl containing one or more hetero atoms; -(CH ₂ ) _0-6 -R ^a ; -(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C2-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, One or more selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl groups C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with a substituent;

R4 and R5 are each independently hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 Alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, trihalo (C1-C4) alkoxy, trihalo (C1 -C4) alkyl, amine substituted with straight or branched C1-C8 alkyl group, or amine substituted with C3-C8 cycloalkyl group;

In the above, the alkyl group means a branched or branched alkyl group, and each R ^C may be independently selected when there are a plurality of R ^Cs in a molecule.

In addition,

It provides a method for preparing the compound of Formula 1.

In addition,

Provided is a pharmaceutical composition for the treatment of a disease associated with the activation of HSP90 comprising a compound of Formula 1, a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof, and a pharmaceutically acceptable carrier.

The novel compounds of the present invention act selectively on cancer cells as anti-cancer agents as HSP90 activity inhibitors, and provide excellent therapeutic effects against various diseases associated with the activation of HSP90.

The present invention relates to a novel compound represented by the following formula (1), a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof:

[Formula 1]

Where

D is C or N,

R1 is hydrogen, halogen, CN, NO ₂ , guanidino, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, trihalo (C1-C4) Alkoxy, trihalo (C 1 -C 4) alkyl,-(CH ₂ ) _0-6 -R ^a , -C2-C6 alkenyl-R ^a ,-(CH ₂ ) _0-6 -OR ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) R ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) OR ^a ,-(CH ₂ ) _{0 ~ 6} -S (O) R ^a ,-(CH ₂ ) _{0 6-} SO ₂ R ^a , -OC (O) R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , -NHC (O) R ^a , -C (O) NR ^a R ^b , -NHC (S) R ^a , -C (S) NR ^a R ^b , -SR ^a , -NHSO ₂ R ^a , -SO ₂ NR ^a R ^b , -OSO ₂ R ^a , or -SO ₂ OR ^a , wherein R ^a and R ^b are each independently hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, COOH Substituted with one or more substituents selected from the group consisting of: -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Unsubstituted C1-C8 alkyl;

,

및

기로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환 또는 비치환된 C3-C8 시클로알킬 또는 C3-C8 헤테로시클로알킬; 또는 C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C3-C8 cycloalkyl or C3-C8 heterocycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of groups; or

,

및

기로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환 또는 비치환된 C6~C18 아릴 또는 C3~C18 헤테로아릴기이며; C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with one or more substituents selected from the group consisting of groups;

Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , tert-butoxycarbonyl (BOC), C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1 ~ C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, C1-C8 alkyl unsubstituted or substituted with halogen, 4- (C1-C8 alkyl) -pyrazin-1-yl, 4- (C1 -C8 alkyl) -pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) alkyl, cycloalkene substituted with carboxyl group, C3-C8 cycloalkyl unsubstituted or substituted with C1-C8 alkyl, C3-C8 heterocycloalkyl unsubstituted or substituted with C1-C8 alkyl, C6-C18 aryl unsubstituted or substituted with C1-C8 alkyl, or C5-C18 heteroaryl unsubstituted or substituted with C1-C8 alkyl;

R2 is hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2- C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, (C1-C4) alkyl substituted with C3-C8 heterocycloalkyl group, trihalo ( C 1 -C 4) alkoxy, trihalo (C 1 -C 4) alkyl, C 1 -C 4 dialkylamino, amines substituted by straight or branched C 1 -C 8 alkyl groups, amines substituted by C 3 -C 8 cycloalkyl groups, C 1 -C 6 Alkylamino (C1-C4) alkyl, C1-C6 dialkylamino (C1-C8) alkyl, C1-C6 alkyleneimino (C1-C4) alkyl group, or-(CH ₂ ) _0-6 -NR ^a , Where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C3-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, One or more substituents selected from the group consisting of -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl A substituted or unsubstituted C6-C18 aryl or C3-C18 heteroaryl group;

R3 is hydrogen; halogen; CN; NO ₂ ; OH; -SH; -COOH; Formyl; Guanidino; -CONH ₂ ; Straight or branched C1-C8 alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C1-C8 alkoxy; Straight or branched C1-C8 alkyl containing one or more hetero atoms; -(CH ₂ ) _0-6 -R ^a ; -(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C2-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, One or more selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl groups C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with a substituent;

R4 and R5 are each independently hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 Alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, trihalo (C1-C4) alkoxy, trihalo (C1 -C4) alkyl, amine substituted with straight or branched C1-C8 alkyl group, or amine substituted with C3-C8 cycloalkyl group;

In the above, the alkyl group means a branched or branched alkyl group, and each R ^C may be independently selected when there are a plurality of R ^Cs in a molecule.

In the above, the hetero atom means O, S and N.

Examples of the heterocycloalkyl group include pyrrolidine, piperidine, piperazine, diazepine, tetrahydrofuran, pyrazolidine, tetrahydrothiophene, pyrazolidine, imidazolidine, oxazolidine, thiazoli Dine, piperidine, morpholine and the like.

Examples of the heteroaryl group include furan, thiophene, pyrrole, pyrazole, imidazole, oxazole, thiazole, pyridine, quinoline, isoquinoline, pyridazine, pyrimidine, pyrazine, triazine, pyran, benzothiazole, di Benzofuran and the like.

Examples of the aryl group include phenyl, naphthyl, biphenyl, thiophenyl, tolyl, xylyl, benzyl, pilolyl, imidazolyl, pyrazinyl, oxazolyl, isoxazolyl, thia Known in this field such as zolyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, purinyl, benzimidazolyl, indolyl, isoquinolyl, quinolyl, quinoxalinyl, etc. It means.

In the present invention, the pharmaceutically acceptable salt of the compound represented by Formula 1 refers to a salt compound form generally used in the art, and specific examples thereof include hydrochloride, acetate, trifluorate, sulfate, Triphosphate, methanesulfonate salt, etc. are mentioned.

HSP90, a molecular chaperone, is a key component of the machinery that drives cancer cells, and is required for the function of several mutagenic or overexpressing signaling proteins that promote cancer cell growth and survival. . This means that HSP90 inhibitors can be effective against a wide variety of cancers. Furthermore, since HSP90 is not only specifically activated in tumor cells but also exists in a high affinity form, HSP90 inhibitors such as the compound of Formula 1 may exhibit high selectivity for tumor cells.

In the compound of Formula 1, preferably

R 1 is hydrogen, halogen, CN, NO ₂ , straight or branched C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkoxy,-(CH ₂ ) _0-6 -R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , wherein R ^a and R ^b are each independently hydrogen; Wherein R ^a and R ^b are each independently hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl;

,

및

기로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환 또는 비치환된 C3-C8 시클로알킬 또는 C3-C8 헤테로시클로알킬; 또는 C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C3-C8 cycloalkyl or C3-C8 heterocycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of groups; or

C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 From the group consisting of -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl group C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with one or more substituents selected;

Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;

R2 is substituted with a hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkyl group (C1- C4) alkyl, (C1-C4) alkyl substituted by C3-C8 heterocycloalkyl group, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl, C1-C4 dialkylamino, straight or branched Amines substituted with C1-C8 alkyl groups in the chain, amines substituted with C3-C8 cycloalkyl groups, C1-C6 alkylamino (C1-C4) alkyl, C1-C6 dialkylamino (C1-C8) alkyl, C1-C6 alkyl alkylene butylimino (C1 ~ C4) group, or - a _{(CH 2) 0 ~ 6 -NR} a, where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl;

R3 is hydrogen; halogen; Straight or branched C1-C8 alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C1-C8 alkoxy; Straight or branched C1-C8 alkyl containing one or more hetero atoms; NO ₂ ; -(CH ₂ ) _0-6 -R ^a ; -(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl unsubstituted or substituted with one or more C1-C4 alkyl groups; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- C3-C8 cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl, or C3-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, C6 ~ C18 unsubstituted or substituted with one or more substituents selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl Aryl or a C3-C18 heteroaryl group;

R4 and R5 are each independently hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkyl groups Substituted (C1-C4) alkyl, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl, amines substituted with straight or branched C1-C8 alkyl groups, or C3-C8 cycloalkyl groups Substituted amine phosphorus.

In the compound of Formula 1, More preferably,

R1 is hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, trifluoromethoxy, trifluoromethyl,-(CH ₂ ) _0-6 -R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , wherein R ^a and R ^b are each independently hydrogen; C1-C8 alkyl unsubstituted or substituted with one or more substituents selected from C1-C4 alkylamino, or C1-C4 dialkylamino;

,

및

기로 이루어진 군으로부터 선택되는 하나 이상의 치환기로 치환 또는 비치환된 C3-C8 시클로알킬 또는 C3-C8 헤테로시클로알킬기이며, C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

A C3-C8 cycloalkyl or C3-C8 heterocycloalkyl group unsubstituted or substituted with one or more substituents selected from the group consisting of

Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;

R2 is hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl group substituted with (C1-C4) alkyl, C3 (C1-C4) alkyl, trifluoromethoxy, trifluoromethyl, C1-C4 dialkylamino, C1-C6 alkylamino (C1-C4) alkyl, C1-C6 dialkylamino substituted with a -C8 heterocycloalkyl group (C1 ~ C8) alkyl, C1-C6-alkylene-butylimino (C1 ~ C4) alkyl, or - a _{(CH 2) 0 ~ 6 -NR} a, where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- C 1 -C 8 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of COOH, —COO (C 1 -C 4 alkyl), —CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl; Is;

R3 is hydrogen; halogen; Straight or branched C1-C8 alkyl; NO ₂ ; C2-C8 alkenyl; C2-C8 alkynyl; -(CH ₂ ) _0-6 -R ^a ; -(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl unsubstituted or substituted with one or more C1-C4 alkyl groups; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- C3-C8 cycloalkyl or C3 unsubstituted or substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo trifluoromethoxy, and trifluoromethyl -C8 heterocycloalkyl; Or halogen, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, C6 ~ C18 unsubstituted or substituted with one or more substituents selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl Aryl or a C3-C18 heteroaryl group;

R 4 and R 5 are each independently substituted with hydrogen, straight or branched C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl group (C 1 -C 4) Alkyl, trifluoromethoxy, or trifluoromethyl groups.

Specific examples of the compound of Formula 1 include the following compounds.

2- (4-hydroxycyclohexylamino) -4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl] -benzamide,

2-bromo-4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine-1 -Yl] -benzamide,

2-bromo-4- (3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide,

2- (4-hydroxycyclohexylamino) -4- (3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) Benzamide,

4- (3,5-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxycyclohexyl Amino) -benzamide,

2-bromo-4- (5-ethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide,

2-Bromo-4- (5-isopropyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide ,

2-Bromo-4- (5-cyclopropylmethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benz amides,

4- (5-cyclopropylmethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydrate Hydroxy-cyclohexylamino) -benzamide,

2- (4-hydroxycyclohexylamino) -4- (5-isopropyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine -1-yl) -benzamide,

4- (5-ethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxy- Cyclohexylamino) -benzamide,

4- (5-benzyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxy- Cyclohexylamino) -benzamide,

2- (4-hydroxycyclohexylamino) -4- (3-methyl-4-oxo-5-thiophen-3-yl-methyl-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl) -benzamide,

4- (5-butyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxy- Cyclohexylamino) -benzamide,

2- (4-hydroxycyclohexylamino) -4- (3-methyl-5-octyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine- 1-yl) -benzamide,

4- [5- (4-fluoro-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -2 -(4-hydroxycyclohexylamino) -benzamide,

2- (4-hydroxycyclohexylamino) -4- [5- (3-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl] -benzamide,

2- (4-hydroxycyclohexylamino) -4- [3-methyl-4-oxo-5- (4-trifluoromethoxy-benzyl) -4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -benzamide,

2- (4-hydroxycyclohexylamino) -4- [5- (2-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl] -benzamide,

4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -2 -(2-morpholin-4-yl-ethylamino) -benzamide,

2- (2-dimethylamino-ethylamino) -4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3, 2-c] pyridin-1-yl] -benzamide,

4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -2 -[3- (2-oxo-pyrrolidin-1-yl) -propylamino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [2- (1-oxy-pyrrolidin-1-yl) -ethylamino] -benzamide,

2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine- 1-yl) -benzamide,

2- (4-hydroxycyclohexylamino) -4- (3,5,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c ] Pyridin-1-yl) -benzamide,

4- (5-ethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4 -Hydroxycyclohexylamino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (3- (trifluoromethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4 , 3-c] pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (3- (trifluoromethyl) -4,5,6,7-tetrahydro-5,6,6-trimethyl-4-oxopyrazolo [4,3-c] pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (5- (cyclopropylmethyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-6,6-dimethyl -4-oxopyrazolo [4,3-c] pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4, 3-c] pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -4,5,6,7-tetrahydro-5,6,6-trimethyl-4-oxopyrazolo [ 4,3-c] pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -5-ethyl-4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyra Zolo [4,3-c] pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (4,5,6,7-tetrahydro-3-isobutyl-6,6-dimethyl-4-oxopyrazolo [4,3-c ] Pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (3,5-bis (cyclopropylmethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4,3-c] pyridin-1-yl) benzamide,

2- ( trans -4-hydroxycyclohexylamino) -4- (5-allyl-4,5,6,7-tetrahydro-3-isobutyl-6,6-dimethyl-4-oxopyrazolo [4 , 3-c] pyridin-1-yl) benzamide,

4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- ( 2-morpholin-4-yl-ethylamino) -benzamide,

2- [3- (2-oxo-pyrrolidin-1-yl) -propylamino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-py Rolo [3,2-c] pyridin-1-yl) -benzamide,

4- (5-ethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,

4- (5-cyclopropylmethyl-3-isobutyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,

4- (5-Cyclopropylmethyl-3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- (4-hydroxycyclohexylamino) -benzamide,

4- (3,5-bis-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- (2-morpholin-4-yl-ethylamino) -benzamide,

2- (4-hydroxycyclohexylamino) -4- [3,6,6-trimethyl-5- (2-methyl-allyl) -4-oxo-4,5,6,7-tetrahydro-pyra Zolo [4,3-c] pyridin-1-yl] -benzamide,

2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine- 1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (2-morpholin-4-yl-ethylamino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [3- (2-oxo-pyrrolidin-1-yl) -propylamino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (2-dimethylamino-ethylamino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (2-pyrrolidin-1-yl-ethylamino) -benzamide,

Aminoacetic acid 4- [2-carbamoyl-5- (3,5,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine- 1-yl) -phenylamino] -cyclohexyl ester,

4- (6,6-dimethyl-3-methylaminomethyl-5-nitro-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl)- 2- (4-hydroxycyclohexylamino) -benzamide,

4- (6,6-dimethyl-5-methylamino-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,

4- (5-cyclopropylamino-6,6-dimethyl-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl ) -2- (4-hydroxycyclohexylamino) -benzamide,

4- (3-Aziridin-1-yl-methyl-5-cyclopropylamino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] Pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,

4- (5-cyclopropylamino-6,6-dimethyl-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl ) -2- (4-hydroxy-piperidin-1-yl-methyl) -benzamide,

4- (5-cyclopropylamino-6,6-dimethyl-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (4-hydroxy-piperazin-1-yl-methyl) -benzamide,

2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3- c] pyridin-1-yl) benzamide,

2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridine- 1-yl) benzamide,

2-((4-acetylpiperazin-1-yl) methyl) -4- (3,6,6-trimethyl-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3 -c] pyridin-1-yl) benzamide,

2-((4-acetylpiperazin-1-yl) methyl) -4- (3,6,6-trimethyl-4-oxo-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl) benzamide,

2-((4-acetylpiperazin-1-yl) methyl) -4- (3,6,6-trimethyl-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3 -c] pyridin-1-yl) benzamide,

2- (1-acetylpiperidin-4-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl-4-oxo Pyrazole [4,3-c] pyridin-1-yl) benzamide,

(S) -tert-butyl 3- (2-carbamoyl-5- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) phenylamino) pyrrolidine-1-carboxylate,

2-((S) -1-acetylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl -4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,

2-((S) -1-benzoylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl -4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,

2-((S) -1-phenylsulfonylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6- Trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,

2-((S) -1-cyclopropylcarbonylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6 -Trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,

2-((S) -1- (2-tert-butyloxycarbonylaminoacetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7 Tetrahydro-3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,

2-((S) -1- (2-aminoacetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3, 6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide hydrochloride,

2-((S) -1- (2- (dimethylamino) acetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro -3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,

5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-diethylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide,

2- [1- (2-cyclopropylamino-acetyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- (1-acetyl-pyrrolidin-3-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro- Pyrazolo4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-methanesulfonyl-pyrrolidin-3-yl-amino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (3-Methyl-butyryl) -pyrrolidin-3-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-ethylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-isobutylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-piperidin-1-yl-acetyl) -pyrrolidin-3-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Morpholin-4-yl-acetyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Isopropylamino-acetyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Pyrrolidin-1-yl-acetyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-ethanesulfonyl-pyrrolidin-3-yl-amino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-dimethylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide,

2- [1- (Boc-sulfamoyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6, 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (Propan-2-sulfonyl) -pyrrolidin-3-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-sulfamoyl-pyrrolidin-3-yl-amino) -benzamide,

2-bromo-4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- 1) -benzamide,

2- [1- (2-cyclobutylamino-acetyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- (1-Carbamoylmethyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Oxo-propyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Oxo-2-phenyl-ethyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-formyl-piperidin-4-yl-amino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Oxo-butyl) -piperidin-4-yl-amino] -benzamide,

3- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine -1-yl) -phenylamino] -pyrrolidine-1-carboxylic acid tert-butyl ester,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-isopropylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide,

2- (1-Chloromethanesulfonyl-pyrrolidin-3-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-ethanesulfonyl-piperidin-4-yl-amino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (Propan-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,

Acetic acid 2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3 -c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -ethyl ester,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-hydroxy-ethyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-dimethylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide,

2- [1- (butane-1-sulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Methyl-propane-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,

{4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -phenylamino] -piperidin-1-yl} -acetic acid methyl ester,

2- [1- (1-Carbamoyl-ethyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-isopropylsulfamoyl-piperidin-4-yl-amino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-cyclopropylsulfamoyl-piperidin-4-yl-amino) -benzamide,

2- (1-Chloromethanesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -propionic acid methyl ester,

2- (1-Boc-1'-benzylsulfamoyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- (1-benzylsulfamoyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (2- (cyclopropylamino-acetyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (1-Methyl-2-oxo-propyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-dimethylcarbamoylmethyl-piperidin-4-yl-amino) -benzamide,

4- [2-carbamoyl-5- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4, 3-c] pyridin-1-yl) -phenylamino] -piperidine-1-carboxylic acid tert-butyl ester,

4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -2- (piperidin-4-yl-amino) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (1-dimethylcarbamoyl-ethyl) -piperidin-4-yl-amino] -benzamide,

2- [1- (Cyclopropylmethyl-sulfamoyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamidetetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (4-cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

(2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyra Zolo [4,3-c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -2-oxo-ethyl) -carbamic acid tert-butyl ester,

2- [1- (2-cyclopropylamino-acetyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoro Methyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,

2- (1- (4-Amido-benzenesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (4-Aminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (1-Methyl-2-morpholin-4-yl-2-oxo-ethyl) -piperidin-4-yl-amino] -benzamide,

2- [1- (3-cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- (1- (3-Amido-benzenesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-methanesulfonylamino-cyclohexylamino) -benzamide,

2- (4-acetylamino-cyclohexylamino) -4- (5-cyclopropyl methyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4, 3-c] pyridin-1-yl) -benzamide,

2- [1- (3-aminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (2-cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (3-Cyano-4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (3-Aminomethyl-4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (4-Bromomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4 , 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Dimethylaminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Piperidin-1-yl-methyl-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [4- (4-Fluoro-benzenesulfonylamino) -cyclohexylamino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Isopropyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Methyl- [1,4] diazepan-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,

4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl}-[1,4] diazepane-1-carboxylic acid tert-butyl ester,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (morpholin-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,

N- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -cyclohexyl} -isonicotinamide,

2- [1- (4-Fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

N- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -cyclohexyl} -nicotinamide,

4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -benzoic acid,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Ethoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,

2- [1- (3-Cyano-4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (3-Amido, 4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (3-acetic acid, 4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,

4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -cyclohexa-1-enecarboxylic acid,

4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -2- [1- (1-methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,

4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -2- {1- [4- (4-methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide,

4- (3-dimethylaminomethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4 -Hydroxycyclohexylamino) -benzamide,

2- (1-benzenesulfonyl-piperidin-4-yl-amino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4 , 3-c] pyridin-1-yl) -benzamide,

2- [4- (4-Fluoro-benzenesulfonylamino) -cyclohexylamino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

N- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -phenylamino] -cyclohexyl} -isonicotinamide,

2- [1- (imidazol-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6 , 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (morpholin-4-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1 -(4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,

2- [1- (1-Methyl-piperidin-4-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- {1- [4- (4-Isopropyl-piperazin-1-yl-methyl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl -4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- {1- [4- (morpholin-4-carbonyl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4-oxo-4 , 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (4-Isopropyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -phenylamino] -piperidine-1-sulfonyl} -cyclohexa-1-enecarboxylic acid,

2- [1- (4-Piperidin-1-yl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (4-Methyl- [1,4] diazepane-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (4-Carbamoylmethyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -phenylamino] -piperidine-1-sulfonyl} -benzoic acid,

2- {1- [4- (4-Isopropyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- ( 4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,

2- {1- [4- (3-Methyl- [1,3] diazepan-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6 -Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- {1 -[4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide,

 4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [ 1- (1-Methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,

4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1 -(1-methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,

2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,7,7-trimethyl-5- Oxo-4a, 5,6,7,8,8a-hexahydro-4H-pyrido [4,3-c] pyridazin-1-yl) -benzamide,

4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- { 1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide,

2- [1- (1-Methyl-piperidin-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- {1- [4- (4-Ethyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- {1- [4- (4-Hydroxy-piperidin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl- 4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (1-cyclopropylmethyl-piperidine-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,

2- [1- (1-Methyl-piperidin-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide, and

2- (1,2,2,6,6-pentamethyl-piperidin-4-yl-amino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl-benzamide.

The present invention also provides a method for preparing a compound represented by the following Chemical Formula 2, wherein the compound of Chemical Formula 1 may also be prepared by this method.

In the above formula, the definitions of D, R1, R2, R3, R4, and R5 are the same as those described in Chemical Formula 1.

Compound of Formula 2,

Preparing a compound of Chemical Formula 5 by reacting a compound of Chemical Formula 3 with a compound of Chemical Formula 4 under a base;

It may be prepared by the step of hydrolyzing the nitrile (CN) group of the compound of Formula 5:

In Chemical Formulas 3 to 5,

X is the same as R1 of Formula 2,

Y is halogen, OH or aldehyde,

The definitions of D, R2, R3, R4 and R5 are the same as described in the above formula (2).

The compound of Formula 3 may be prepared by reacting a compound of Formula 6 with a compound of Formula 7 under a base:

In Chemical Formulas 6 and 7,

The definitions of X, Y, D, R2, R4 and R5 are the same as described in the above Chemical Formulas 3 to 5.

In addition, the compound of Formula 3 may be prepared by reacting a compound of Formula 8 or a compound of Formula 9 with a compound of Formula 10 under a base:

In Chemical Formulas 8 to 10,

The definitions of X, R2, R4 and R5 are the same as those described in the above Chemical Formulas 3 to 5.

Bases and reaction solvents used in the above compounds can be used without limitation, those commonly used in the art. For example, NaH, K ₂ CO ₃ , KOH, NaOH, LiOH, Na ₂ CO ₃ , n-Buli, sec-Buli, etc. may be used as the base, and the reaction DMSO, DMF, NMP, THF, Hexane, or their Mixed solvents and the like can be used.

In addition, the method of preparing the compound of Formula 2 may be exemplified by the following reaction.

[Synthesis method of pyridinone derivative of formula 2]

In the above scheme, the definitions of X, Y, D, R2, R3, R4 and R5 are the same as those described in Chemical Formulas 3 to 5,

R1 is the same as described in Formula 2,

R means an atom or compound that meets the definition above R1.

Hereinafter, a method of preparing the compound of Formula 2 will be described in more detail.

(1) Method for preparing compound of formula (1) having pyrrolopyridinone skeleton

The compound of formula (2) having a pyrrolopyridinone skeleton can be prepared by a general method, and the following four kinds of production methods can be mentioned as specific examples.

Compounds having a pyrrolopyridinone skeleton of the compound of Formula 2 and R4 and R5 are hydrogen may be prepared according to the synthesis route according to Scheme 1.

Scheme 1

When the synthesis of the scheme 1 divided by stages described.

Scheme 1-1

Toluene (1 L), Compound 3 (13.1 g, 52.1 mmol) and p- TsOH (29.7 g, 156.2 mmol) were added to Compound 1 (12.2 g, 57.3 mmol), and a Dean-Stock apparatus was installed. Stirred at reflux. The solvent of the reaction mixture was concentrated, neutralized in aqueous NaHCO ₃ solution, extracted with CH ₂ Cl ₂ solvent and washed with water. The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was concentrated under reduced pressure. The resulting solid was filtered to afford compound 4 (7.3 g, 42%).

Scheme 1-2

Compound 4 (5 g, 15.2 mmol), synthesized above, was dissolved in N , N -dimethylformamide (100 mL), and NaH (60% in mineral oil, 909 mg, 22.7 mmol) was added at 0 ^o C. The resulting H ₂ gas was removed under reduced pressure and then bromoethyl cyclopropane (5.1 g, 37.9 mmol) was added and then stirred at room temperature for 2 hours. The reaction mixture was neutralized in 1 N aqueous HCl solution and water and then extracted in EtOAc solvent. The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was concentrated under reduced pressure and separated by silica gel column chromatography (hexane / EtOAc, 3: 1) to give compound 5 (4.8 g, 83%).

Scheme 1-3

To 5 (1 g, 2.60 mmol) of the compound prepared in N - was dissolved in methyl-2-pyrrolidinone (N -methyl-2-pyrrolidinone, 10 mL), trans-4-amino-cyclohexanol (trans- 4-aminocyclohexanol, 1.5 g, 13.0 mmol) was added. The reaction mixture was irradiated with microwaves and stirred at 200 ^° C. for 1.5 hours. After the reaction was neutralized with 1 N HCl and water, extracted with EtOAc solvent, washed with brine. The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was concentrated under reduced pressure and separated by silica gel column chromatography (CH ₂ Cl ₂ / MeOH, 20: 1) to obtain compound 6 . The synthesis was carried out four times using a total of 3.6 g of Compound 5 in the same manner as described above. As a result, 4.2 g of Compound 6 containing a small amount of N -methyl-2-pyrrolidinone solvent was obtained.

Trans-4-amino-cyclohexanol (trans-4-aminocyclohexanol), cis-4-amino-cyclohexanol (cis-4-aminocyclohexanol) or 4-amino-cyclohexanol (4-aminocyclohexanol, mixture) in the reaction step It can be used to synthesize the desired compound in the form of trans, cis or mixed (racemic), so that the final compound can also be obtained in trans, cis or mixed (racemic) form in a later step.

Scheme 1-4

Compound 6 ( 4.2 g (including NMP solvent), 10.2 mmol), synthesized above, was dissolved in EtOH / DMSO (4: 1, 100 mL) solution, and then H ₂ O ₂ (30% in H ₂ O, 5.2 mL, 51.0). mmol), 1 M aq. NaOH (20.4 mL, 20.4 mmol) was added and stirred at rt for 2 h. The reaction mixture was neutralized in 1 N HCl aqueous solution and water, and then extracted with CH ₂ Cl ₂ solvent. The organic layer was dried over Na ₂ SO ₄ and filtered. The solvent was concentrated under reduced pressure. The solid produced in EtOAc solvent was filtered and then washed again in benzene solvent and dried under reduced pressure to give the desired compound 7 (1.7 g, 43%, 2 step overall yield).

Compounds having a pyrrolopyridinone skeleton in the compound of Formula 1 and R4 and R5 are not hydrogen may be prepared according to the synthesis route according to Scheme 2 below.

Scheme 2

When the synthesis of the reaction scheme 2 is described by dividing step by step as follows.

Scheme 2-1

Dissolve 3-amino-3-methyl butyric acid 8 (3-amino-3-methyl butyric acid , 10 g, 85.3 mmol) in dioxane / H ₂ O (2: 1, 450 mL), and then K. ₂ CO ₃ (35 g, 256 mmol) was added at rt, Boc ₂ O (20 g, 93.9 mmol) at 0 ^° C. and stirred at rt for 2 h. The reaction mixture was poured into H ₂ O and EtOAc solvents, the water layer was separated with a separatory funnel, the pH was adjusted to 4-5 with aqueous aq. Citiric acid, and extracted with CH ₂ Cl ₂ . , Dried over Na ₂ SO ₄ , filtered, and then the solvent was removed under reduced pressure.

Concentrated reactant 9 ( quant.) Was dissolved in CH ₂ Cl ₂ (300 mL), then Meldrum's acid 10 (13.5 g, 93.8 mmol), DMAP (12.5 g, 102.3 mmol) was added at room temperature, EDCI (19.6 g, 102.3). mmol) was added at 0 ^° C. and stirred at rt for at least 12 h. The reaction mixture was aq. After washing with KHSO ₄ (400 mL, 3 times), the organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was removed under reduced pressure. The reaction intermediate was dissolved in EtOAc (300 mL), stirred at boiling point for 4 hours or more, and after the reaction was completed, the solvent was removed under reduced pressure, and the resulting solid was filtered to give the compound 11 ( 13.6 g, 66%) as white. Obtained as a solid.

Scheme 2-2

Compound 11 (13.6 g, 56.4 mmol) synthesized above was dissolved in tetrahydrofuran (150 mL), and then 1-amino-2-propanol (1-amino-2-propanol, 5.08 g, 67.6 mmol), 4A (o) molecular sieve (molecularsieve, 20 g) was added thereto, followed by stirring at 80 ^° C. for 3 hours. After stirring, the solution from which the reaction mixture was passed through celite was concentrated under reduced pressure and CH ₂ Cl ₂ was added. The solid produced in CH ₂ Cl ₂ solvent was filtered to give compound 12 (8.7 g, 52%).

Scheme 2-3

Compound 12 (8.7 g, 29.2 mmol) synthesized above was dissolved in anhydrous dimethyl sulfoxide (100 mL), and then Pd (PPh ₃ ) ₄ (674 mg, 0.58 mmol, 2 mol%), mesityl bromide, 5.8 g, 29.2 mmol), K ₂ CO ₃ (8 g, 58.3 mmol) were added and reacted under nitrogen stream at 150 ^° C. for 3.5 h. After the reaction, water was poured into the mixture, followed by extraction with ether. The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was removed under reduced pressure and separated by silica gel column chromatography (hexane / EtOAc, 2: 1) to give compound 14 (4 g, 46%).

Scheme 2-4

Compound 14 (450 mg, 1.62 mmol) synthesized above was dissolved in dimethyl sulfoxide (5 mL), NaH (60% in mineral oil, 129 mg, 3.23 mmol) was added, and the resulting H ₂ gas was removed under reduced pressure. After the removal, 2-bromo-4-fluorobenzonitrile (2-bromo-4-fluorobenzonitrile, 483 mg, 2.43 mmol) was added thereto, followed by stirring at room temperature for 12 hours or more. The reaction mixture was neutralized with 1 N HCl and water and extracted with EtOAc. The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was removed under reduced pressure and separated by silica gel column chromatography (hexane / EtOAc, 5: 1) to give compound 15 (560 mg, 76%).

Scheme 2-5

Compound 15 (500 mg, 1.09 mmol) synthesized above was dissolved in CH ₂ Cl ₂ (5 mL), trifluoroacetic acid (1 mL) was added thereto, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was aq. Neutralized with NaHCO ₃ and water and extracted with CH ₂ Cl ₂ . The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was concentrated under reduced pressure. The resulting solid was filtered to afford compound 16 (370 mg, 91%).

Scheme 2-6

The compound prepared in 16 (370 mg, 1.03 mmol) of N, N - dimethyl formamide was dissolved in (N, N -dimethylformamide, 5 mL ), NaH (60% in ^{0 o C in mineral oil, 124} mg, 3.10 mmol) was added and the resulting H ₂ gas was removed under reduced pressure, methyl iodide (733 mg, 5.16 mmol) was added and stirred at room temperature for 4 hours. The reaction mixture was neutralized in 1 N aqueous HCl solution and water and then extracted in EtOAc solvent. The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was concentrated under reduced pressure, separated by silica gel column chromatography (hexane / EtOAc, 2: 1) to give compound 17 (320 mg, 83%).

 Scheme 2-7

The compound 17 (320 mg, 0.86 mmol) prepared in N - was dissolved in methyl-2-pyrrolidinone (N -methyl-2-pyrrolidinone, 5 mL), trans-4-amino-cyclohexanol (trans- 4-aminocyclohexanol, 198 mg, 1.72 mmol) was added. The reaction mixture was irradiated with microwaves and stirred at 200 ^° C. for 1.5 hours. After the reaction was neutralized with 1 N HCl and water, extracted with EtOAc solvent, washed with brine. The organic layer was dried over Na ₂ SO ₄ , filtered, and the solvent was concentrated under reduced pressure and separated by preparative thin layer chromatography (prep. Thin layer chromatography, CH ₂ Cl ₂ / MeOH, 30: 1) to give a compound 18 ( 210 mg, 58%).

Trans-4-amino-cyclohexanol (trans-4-aminocyclohexanol), cis-4-amino-cyclohexanol (cis-4-aminocyclohexanol) or 4-amino-cyclohexanol (4-aminocyclohexanol, mixture) in the reaction step It can be used to synthesize the desired compound in the form of trans, cis or mixed (racemic), so that the final compound can also be obtained in trans, cis or mixed (racemic) form in a later step.

Scheme 2-8

Compound 18 ( 210 mg, 0.52 mmol) synthesized above was dissolved in EtOH / DMSO (4: 1, 5 mL) solution, and then H ₂ O ₂ (30% in H ₂ O, 0.26 mL, 2.58 mmol), 1 M aq. NaOH (1.03 mL, 1.03 mmol) was added and stirred at rt for 1 h. The reaction mixture was neutralized in 1 N HCl aqueous solution and water, and then extracted with CH ₃ Cl solvent. The organic layer was dried over Na ₂ SO ₄ and filtered. The solvent was concentrated under reduced pressure. The solid produced in CH ₂ Cl ₂ / EtOAc solvent was filtered, washed again in benzene solvent and dried under reduced pressure to afford the desired compound 19 (214 mg, quant.). Target compound 19 is a compound corresponding to Example 25 of the present invention.

By changing the degree of introducing an appropriate substituent to prepare a compound of the present invention in the above schemes, those skilled in the art can prepare the compounds of the present invention.

According to the above reaction scheme,

(2) Method for preparing compound of formula (1) having pyrazolopyridinone skeleton

Compounds of formula (1) having a pyrazolopyridinone skeleton can be prepared by a general method, specifically, according to the synthetic route according to Schemes 3 and 4.

Scheme 3

In the synthesis, the synthesis proceeds to compound No. 22, and R1, R3 introduction and conversion of nitrile to amide in Formula 1 are the pathways for synthesizing compound No. 19 in compound No. 17 of Schemes 2-7 and 2-8. Follow.

Scheme 3-1

11. The compound synthesized in (1.0 g, 4.145 mmol), p - toluenesulfonyl azide Hiratsuka (p -toluenesulfonylhyrazide, 0.809 g, 4.352 mmol) and p - toluenesulfonic acid (p -toluenesulfonic acid, 0.08 g, 0.415 mmol) to It was dissolved in toluene (40 mL) and refluxed to 130 ° C. After 30, the transparent reaction solution was cooled to -5 ° C and left for 10 minutes. The precipitated target was filtered under reduced pressure and washed with toluene (10 mL). The filtered precipitate was dried to give yellow intermediate 20 (1.257 g). Intermediate 20 was dissolved in anhydrous THF (20 mL), and triethylamine (1.42 mL, 10.16 mmol) and trifluoroacetic anhydride (1.14 mL, 8.12 mmol) were slowly added dropwise at 0 ° C. After stirring for 20 minutes, the reaction solution was stirred for 3 hours at 50 ℃ and then cooled to ~ 5 ℃. A mixture of 1 N NaOH (9 mL) and MeOH (9 mL) was added, followed by extraction with EtOAc (30 mL X 4), followed by drying over anhydrous Na ₂ S0 ₄ and drying under reduced pressure, followed by chromatography (hexane: EtOAc = 1: 4). Separation and purification gave the target compound 21 (0.33 g).

¹ H NMR (DMSO-d 6, 300 MHz) δ 1.24 (s, 6H), 2.88 (s, 2H), 7.49 (s, 1H).

Scheme 3-2

Compound 21 (0.519 g, 2.226 mmol) obtained above, K ₂ CO ₃ (1.02 g, 5.564 mmol), and 2-bromo-4-fluorobenzonitrile (2-bromo-4-fluorobenzonitrile, 0.534 g, 2.671). mmol) was dissolved in DMF (10 mL) and stirred at 60 ° C. for 4 hours. After completion of the reaction, water (30 mL) was added, extracted with EtOAc (40 mL X 3), washed with brine (10 mL), dried over MgSO ₄ , dried under reduced pressure, purified by chromatography and the target compound. 22 yellow solid (0.818 g) was obtained.

¹ H NMR (DMSO-d6, 300 MHz) δ 1.24 (s, 6H), 3.17 (s, 2H), 7.82 (brs, 1H), 7.87 (dd, J = 2.1 and 8.4 Hz, 1H), 8.17 (d , J = 2.1 Hz, 1H), 8.20 (s, 1H).

Scheme 4

Compound 11 (2.4 g, 10 mmol), DMAP (1.8 g, 15 mmol), and cyclopropane acid (cyclopropane acid, 1.29 ml 15 mmol) synthesized above were dissolved in dichloromethane (40 mL) and cooled to 0 ° C. EDC (2.8 g, 15 mmol) was slowly added dropwise for 20 minutes. After confirming the reaction, the solvent was removed, diluted with KHSO ₃ aqueous solution, extracted with ethyl acetate, and the solvent was removed. Then, Compound 23 was obtained by silica gel chromatography (EtOAc: Hea = 3: 1). Bromo-cyano benzhydrazine (2.12 g 10 mmol) was added to compound 23, and 10 ml of ethanol / acetic acid (3: 1) solvent was added to dissolve the solution, followed by irradiation with microwaves (150 ° C. for 15 minutes). Proceeded.

After confirming the completion of the reaction, the reaction was cooled in ice water for 1 hour, 12 ml of water was added thereto, and the precipitated target was filtered under reduced pressure and washed with ethanol (10 mL). The filtered precipitate was dried to give yellow intermediate compound 24 (1.257 g).

The synthesis proceeds to compound No. 24, and the introduction of R1 and R3 of Formula 1 depends on the route for synthesizing compound No. 19 from compounds No. 17 of Schemes 2-7 and 2-8.

The present invention also provides

It relates to a pharmaceutical composition for the treatment of a disease associated with the activation of HSP90 comprising a compound of Formula 1, a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof, and a pharmaceutically acceptable carrier.

Diseases related to activation of HSP90 include cancer (solid cancer, uterine cancer, breast cancer, stomach cancer, lung cancer, kidney cancer, colon cancer, melanoma cancer, pancreatic cancer, etc .; hematologic cancer, acute leukemia, chronic leukemia, etc.), carcinoma and inflammatory diseases. Pain, headache, fever, asthma, bronchitis, tendinitis, bursitis, eczema, psoriasis, dermatitis, autoimmune infections, Crohn's disease, Hodgkin's disease, diabetes, rheumatic fever, ischemia, degenerative neuropathy (aging) Dementia, Parkinson's disease, Kennedy's disease with muscle degeneration associated with polyQ disease), Alzheimer's disease, CNS disorders, and immune disorders.

"Pharmaceutically acceptable carrier" in the pharmaceutical composition refers to solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, available for pharmaceutical administration. The use of such media or agents for pharmaceutically active ingredients is well known in the art. Supplementary active compounds can also be included in the pharmaceutical compositions.

The pharmaceutical composition of the present invention may be administered parenterally, topically, orally or locally for therapeutic treatment. For example, the pharmaceutical composition may include various aqueous carriers such as water, buffered water, 0.4% saline, 0.3% glycine, and may also include proteins that enhance stability such as albumin, lipoprotein, globulin, and the like. Thus, the pharmaceutical composition can be sterilized by conventional, well-known sterilization techniques, can be packaged for use, and can be lyophilized by filtration under sterile conditions. The freeze-dried pharmaceutical composition is mixed with sterile solution prior to administration.

Oral compositions generally include an inert diluent or an edible carrier. The active compound is enclosed in gelatin capsules or compressed into tablets. For oral therapeutic administration, the active compounds may be included with excipients and prepared in the form of tablets, troches, or capsules. Pharmaceutically available binders, and / or adjuvants may be included as part of the composition. The tablets, pills, capsules, troches, and the like may comprise one or more of the following components: compounds (eg, microcrystalline cellulose, tragacanth gum or gelatin); Excipients (eg starch or lactose), disintegrating agents (eg alginic acid, primogel, or corn starch); Lubricants (eg, magnesium stearate or steotes); Glidants (eg, colloidal silicon dioxide); Sweeteners (eg, sucrose or saccharin); Or flavoring agents (eg peppermint, methyl salicylate, or orange flavor).

For administration by inhalation, the active compound is delivered in the form of an aerosol spray from a compression vessel or dispenser or nebulizer containing a suitable propellant (eg a gas such as carbon dioxide).

Systemic administration may be by transmucosal or transdermal means. Penetrating agents suitable for the barrier to be permeated for transmucosal or transdermal administration are used. Such penetrants are generally known in the art and, for example, detergents, bile salts, and fusidic acid derivatives are used for mucosal transfusions. Transmucosal administration can be achieved through the use of nasal sprays or suppositories. For transdermal administration, the active compounds can be prepared in the form of ointments, salves, gels, or creams that are generally known in the art.

In one embodiment, the active compound can be prepared with a carrier that controls the rapid absorption of the active compound into the body, such as a controlled release formulation that includes an implanted and microencapsulated delivery system. Such carriers may be biodegradable or bioavailable polymers, specifically ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, polylactic acid, and the like.

It is desirable to prepare oral or parenteral pharmaceutical compositions in dosage unit form for ease of administration and unity of dosage. Dosage unit form as used herein refers to physically discrete units suited as a single dose for the patient being treated. Each unit contains a predetermined amount of active ingredient calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The details of the dosage unit form of the invention depend directly on and can be determined by the unique features of the active ingredient and the particular therapeutic effect to be achieved and the technique of preparing the active compound for the treatment of the individual.

Toxicity and therapeutic effects of the active compounds can be determined in standard pharmaceutical procedures or experimental animals in cell culture, for example, in the determination of LD50 (fatal to 50% of the population) and ED50 (therapeutically effective amount to 50% of the population). Can be determined by. The ratio of the amount between toxic and therapeutic effects is a therapeutic indicator and it can be expressed as LD50 / ED50. Preferred are compounds that exhibit large therapeutic indices. Although compounds with toxic side effects may be used, it is important to design a delivery system that allows such active compounds to reach the desired site of tissue in order to minimize potential damage and reduce side effects in non-pathological cells. .

Data from cell culture assays and animal studies can be used to formulate a range of dosages for use in humans. The dosage of such compounds should preferably be in the range of circulating concentrations comprising ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. A therapeutically effective amount for any compound of the present invention can be initially estimated by cell culture assays. The amount can be formulated in an animal model to achieve a range of circulating plasma concentrations, including IC ₅₀ (concentration of test compound that achieves half inhibition of symptom maximum) determined in cell culture. Such information can be used to more accurately determine the amount available to humans. Levels in plasma can be measured, for example, by high performance liquid chromatography.

The pharmaceutical composition of the present invention may include the compound of formula 1, a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof as an active ingredient alone or in combination with other pharmaceutically active agents.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following examples are intended to illustrate the present invention more specifically, but the scope of the present invention is not limited by the following examples. The following examples can be appropriately modified and changed by those skilled in the art within the scope of the present invention.

Representative examples of the compound of formula 1 of the present invention are briefly shown in Table 1 below.

The structures of the following compound compounds were confirmed using mass spectrometry (ESI-MS).

Example 1: 2- (4-hydroxycyclohexylamino) -4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro- Pyrrolo [3,2-c] pyridin-1-yl] -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) δ 1.35-1.49 (m, 4H), 2.01-2.12 (m, 4H), 2.41 (s, 3H), 2.78 (t, J = 6.9 Hz, 2H), 3.27 ( br s, 1H), 3.42 (t, J = 6.9 Hz, 2H), 3.65-3.79 (m, 2H), 3.79 (s, 3H), 4.64 (s, 2H), 5.76 (br s, 2H), 6.27 (dd, J = 8.4 and 1.8 Hz, 1H), 6.47 (d, J = 1.8 Hz, 1H), 6.61 (s, 1H), 6.85 (d, J = 8.7 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 7.40 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 7.5 Hz, 1H)

Example 2: 2-bromo-4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c ] Pyridin-1-yl] -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) δ 2.37 (s, 3H), 2.79 (t, J = 6.9 Hz, 2H), 3.44 (t, J = 6.9 Hz, 2H), 3.80 (s, 3H), 4.63 (s, 2H), 6.01 (br s, 1H), 6.35 (br s, 1H), 6.59 (s, 1H), 6.86 (d, J = 8.7 Hz, 2H), 7.21 (dd, J = 8.4 and 2.1 Hz, 1H), 7.25 (d, J = 8.7 Hz, 2H), 7.48 (d, J = 2.1 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H)

Example 3: 2-Bromo-4- (3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl ₃ + DMSO-d ₆ , 300 MHz) δ 2.34 (s, 3H), 2.85 (t, J = 6.9 Hz, 2H), 3.52 (t, J = 6.9 Hz, 2H), 5.97 (br) s, 1H), 6.61 (s, 1H), 6.85 (br s, 1H), 7.02 (br s, 1H), 7.29 (dd, J = 8.4 and 2.1 Hz, 1H), 7.54 (d, J = 2.1 Hz , 1H), 7.66 (d, J = 8.4 Hz, 1H)

Example 4: 2- (4-hydroxycyclohexylamino) -4- (3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine- 1-yl) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.13-1.40 (m, 4H), 1.78-1.83 (m, 2H), 1.94-1.98 (m, 2H), 2.21 (s, 3H), 2.82 (t , J = 6.6 Hz, 2H), 3.30-3.50 (m, 4H), 4.54 (d, J = 3.9 Hz, 1H), 6.47 (d, J = 8.7 Hz, 1H), 6.58 (s, 1H), 6.82 (s, 1H), 6.97 (br s, 1H), 7.17 (br s, 1H), 7.68 (d, J = 8.7 Hz, 1H), 7.85 (br s, 1H), 8.39 (d, J = 7.8 Hz , 1H)

Example 5: 4- (3,5-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydrate Roxy-cyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.12-1.40 (m, 4H), 1.78-1.82 (m, 2H), 1.93-1.99 (m, 2H), 2.21 (s, 3H), 2.89 (s , 3H), 2.93 (t, J = 6.9 Hz, 2H), 3.33-3.50 (m, 2H), 3.48 (t, J = 6.9 Hz, 2H), 4.55 (d, J = 4.2 Hz, 1H), 6.47 (dd, J = 8.4 and 1.8 Hz, 1H), 6.58 (d, J = 1.8 Hz, 1H), 6.83 (s, 1H), 7.17 (br s, 1H), 7.67 (d, J = 8.4 Hz, 1H ), 7.86 (br s, 1 H), 8.40 (d, J = 7.8 Hz, 1 H)

Example 6: 2-bromo-4- (5-ethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -Benzamide

¹ H NMR (CDCl ₃ , 300 MHz) δ 1.21 (t, J = 7.2 Hz, 3H), 2.33 (s, 3H), 2.88 (t, J = 6.6 Hz, 2H), 3.48 (q, J = 7.2 Hz , 2H), 3.54 (t, J = 6.6 Hz, 2H), 5.97 (br s, 1H), 6.41 (br s, 1H), 6.57 (s, 1H), 7.23 (dd, J = 8.4 and 2.1 Hz, 1H), 7.49 (d, J = 2.1 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H)

Example 7: 2-bromo-4- (5-isopropyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl ) -Benzamide

¹ H NMR (CDCl ₃ , 500 MHz) δ 1.17 (d, J = 7.0 Hz, 6H), 2.35 (s, 3H), 2.84 (t, J = 6.5 Hz, 2H), 3.43 (t, J = 6.5 Hz , 2H), 5.03 (septet, J = 6.5 Hz, 1H), 5.89 (br s, 1H), 6.30 (br s, 1H), 6.59 (s, 1H), 7.25 (dd, J = 8.5 and 2.0 Hz, 1H), 7.51 (d, J = 2.0 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H)

Example 8: 2-bromo-4- (5-cyclopropylmethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine-1- Sun) -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) δ 0.25-0.30 (m, 2H), 0.49-0.54 (m, 2H), 0.99-1.10 (m, 1H), 2.34 (s, 3H), 2.90 (t, J = 6.6 Hz, 2H), 3.39 (d, J = 6.9 Hz, 2H), 3.64 (t, J = 6.6 Hz, 2H), 5.95 (br s, 1H), 6.38 (br s, 1H), 6.58 (s , 1H), 7.24 (dd, J = 8.1 and 2.1 Hz, 1H), 7.50 (d, J = 2.1 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H)

Example 9: 4- (5-cyclopropylmethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.20-0.25 (m, 2H), 0.41-0.47 (m, 2H), 0.94-1.03 (m, 1H), 1.13-1.40 (m, 4H), 1.78 -1.83 (m, 2H), 1.94-1.98 (m, 2H), 2.22 (s, 3H), 2.92 (t, J = 6.6 Hz, 2H), 3.27 (d, J = 6.9 Hz, 2H), 3.35- 3.51 (m, 2H), 3.58 (t, J = 6.9 Hz, 2H), 4.54 (d, J = 3.6 Hz, 1H), 6.48 (dd, J = 8.4 and 1.8 Hz, 1H), 6.59 (d, J = 1.8 Hz, 1H), 6.83 (s, 1H), 7.16 (br s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.88 (br s, 1H), 8.40 (d, J = 7.8 Hz , 1H)

Example 10 2- (4-hydroxycyclohexylamino) -4- (5-isopropyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2 -c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.09 (d, J = 6.9 Hz, 6H), 1.17-1.40 (m, 4H), 1.78-1.83 (m, 2H), 1.94-1.98 (m, 2H ), 2.22 (s, 3H), 2.86 (t, J = 6.6 Hz, 2H), 3.37 (t, J = 6.6 Hz, 2H), 3.43-3.51 (m, 2H), 4.55 (br s, 1H), 4.79 (septet, J = 6.9 Hz, 1H), 6.46 (dd, J = 8.4 and 1.8 Hz, 1H), 6.55 (d, J = 1.8 Hz, 1H), 6.82 (s, 1H), 7.16 (br s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.85 (br s, 1H), 8.40 (d, J = 7.8 Hz, 1H)

Example 11: 4- (5-ethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4 -Hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.06 (t, J = 6.9 Hz, 3H), 1.13-1.40 (m, 4H), 1.78-1.82 (m, 2H), 1.95-1.98 (m, 2H ), 2.21 (s, 3H), 2.91 (t, J = 6.3 Hz, 2H), 3.41 (q, J = 6.9 Hz, 2H), 3.49 (t, J = 6.3 Hz, 2H), 3.37-3.51 (m , 2H), 4.54 (d, J = 3.9 Hz, 1H), 6.47 (d, J = 8.4 Hz, 1H), 6.58 (s, 1H), 6.82 (s, 1H), 7.17 (br s, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.85 (br s, 1H), 8.40 (d, J = 7.8 Hz, 1H)

Example 12: 4- (5-benzyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4 -Hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.10-1.39 (m, 4H), 1.76-1.81 (m, 2H), 1.92-1.97 (m, 2H), 2.25 (s, 3H), 2.91 (t , J = 6.6 Hz, 2H), 3.35-3.45 (m, 2H), 3.43 (t, J = 6.6 Hz, 2H), 4.53 (d, J = 3.9 Hz, 1H), 4.61 (s, 2H), 6.47 (d, J = 8.4 Hz, 1H), 6.59 (s, 1H), 6.85 (s, 1H), 7.16 (br s, 1H), 7.25-7.37 (m, 5H), 7.67 (d, J = 8.4 Hz , 1H), 7.84 (br s, 1H), 8.38 (d, J = 8.1 Hz, 1H)

Example 13: 2- (4-hydroxycyclohexylamino) -4- (3-methyl-4-oxo-5-thiophen-3-yl-methyl-4,5,6,7-tetrahydro- Pyrrolo [3,2-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.12-1.38 (m, 4H), 1.77-1.81 (m, 2H), 1.93-1.97 (m, 2H), 2.24 (s, 3H), 2.91 (t , J = 6.6 Hz, 2H), 3.35-3.46 (m, 2H), 3.44 (t, J = 6.6 Hz, 2H), 4.54 (d, J = 3.9 Hz, 1H), 4.58 (s, 2H), 6.47 (dd, J = 8.4 and 1.5 Hz, 1H), 6.58 (d, J = 1.5 Hz, 1H), 6.84 (s, 1H), 7.04 (d, J = 4.8 Hz, 1H), 7.16 (br s, 1H ), 7.36 (d, J = 1.8 Hz, 1H), 7.50 (dd, J = 4.8 and 1.8 Hz, 1H), 7.67 (d, J = 8.7 Hz, 1H), 7.85 (br s, 1H), 8.39 ( d, J = 8.7 Hz, 1H)

Example 14 4- (5-butyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4 -Hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.91 (t, J = 7.2 Hz, 3H), 1.12-1.40 (m, 6H), 1.48 (quintet, J = 7.2 Hz, 2H), 1.78-1.82 ( m, 2H), 1.94-1.98 (m, 2H), 2.21 (s, 3H), 2.90 (t, J = 6.6 Hz, 2H), 3.32-3.50 (m, 2H), 3.36 (t, J = 7.2 Hz , 2H), 3.48 (t, J = 6.6 Hz, 2H), 4.54 (d, J = 3.9 Hz, 1H), 6.47 (dd, J = 8.4 and 1.8 Hz, 1H), 6.58 (d, J = 1.8 Hz , 1H), 6.82 (s, 1H), 7.16 (br s, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.85 (br s, 1H), 8.40 (d, J = 7.5 Hz, 1H)

Example 15 2- (4-hydroxycyclohexylamino) -4- (3-methyl-5-octyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2- c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.86 (t, J = 6.9 Hz, 3H), 1.13-1.39 (m, 14H), 1.42-1.52 (m, 2H), 1.78-1.81 (m, 2H ), 1.94-1.99 (m, 2H), 2.21 (s, 3H), 2.89 (t, J = 6.9 Hz, 2H), 3.32-3.49 (m, 2H), 3.35 (t, J = 7.2 Hz, 2H) , 3.47 (t, J = 6.9 Hz, 2H), 4.55 (d, J = 3.9 Hz, 1H), 6.47 (d, J = 8.4 Hz, 1H), 6.57 (s, 1H), 6.82 (s, 1H) , 7.17 (br s, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.86 (br s, 1H), 8.40 (d, J = 7.8 Hz, 1H)

Example 16: 4- [5- (4-fluoro-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine-1- Ill] -2- (4-hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.20-1.38 (m, 4H), 1.77-1.81 (m, 2H), 1.93-1.99 (m, 2H), 2.25 (s, 3H), 2.91 (t , J = 6.6 Hz, 2H), 3.33-3.45 (m, 2H), 3.42 (t, J = 6.6 Hz, 2H), 4.54 (d, J = 3.3 Hz, 1H), 4.59 (s, 2H), 6.47 (d, J = 8.4 Hz, 2H), 6.59 (s, 1H), 6.85 (s, 1H), 7.16 (d, J = 8.7 Hz, 1H), 7.16 (br s, 1H), 7.35 (dd, J = 8.7 and 6.0 Hz, 2H), 7.67 (d, J = 8.7 Hz, 1H), 7.85 (br s, 1H), 8.39 (d, J = 7.8 Hz, 1H)

Example 17 2- (4-hydroxy-cyclohexylamino) -4- [5- (3-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro- Pyrrolo [3,2-c] pyridin-1-yl] -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.19-1.38 (m, 4H), 1.77-1.81 (m, 2H), 1.93-1.99 (m, 2H), 2.25 (s, 3H), 2.91 (t , J = 6.3 Hz, 2H), 3.32-3.50 (m, 2H), 3.42 (t, J = 6.3 Hz, 2H), 3.74 (s, 3H), 4.54 (d, J = 3.0 Hz, 1H), 4.58 (s, 2H), 6.48 (d, J = 8.4 Hz, 1H), 6.59 (s, 1H), 6.82-6.89 (m, 4H), 7.17 (br s, 1H), 7.25 (t, J = 7.5 Hz , 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.85 (br s, 1H), 8.39 (d, J = 7.5 Hz, 1H)

Example 18 2- (4-hydroxycyclohexylamino) -4- [3-methyl-4-oxo-5- (4-trifluoromethoxy-benzyl) -4,5,6,7-tetra Hydro-pyrrolo [3,2-c] pyridin-1-yl] -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.10-1.40 (m, 4H), 1.78-1.82 (m, 2H), 1.95-1.98 (m, 2H), 2.26 (s, 3H), 2.94 (t , J = 5.7 Hz, 2H), 3.34-3.47 (m, 2H), 3.47 (t, J = 5.7 Hz, 2H), 4.56 (d, J = 3.3 Hz, 1H), 4.64 (s, 2H), 6.49 (d, J = 8.1 Hz, 1H), 6.60 (s, 1H), 6.87 (s, 1H), 7.19 (br s, 1H), 7.34 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H), 7.69 (d, J = 8.1 Hz, 1H), 7.87 (br s, 1H), 8.41 (d, J = 7.8 Hz, 1H)

Example 19: 2- (4-hydroxycyclohexylamino) -4- [5- (2-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro- Pyrrolo [3,2-c] pyridin-1-yl] -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.13-1.41 (m, 4H), 1.77-1.82 (m, 2H), 1.94-1.98 (m, 2H), 2.23 (s, 3H), 2.93 (t , J = 6.3 Hz, 2H), 3.33-3.50 (m, 2H), 3.48 (t, J = 6.3 Hz, 2H), 3.82 (s, 3H), 4.54 (s, 1H), 4.56 (s, 2H) , 6.49 (d, J = 8.4 Hz, 1H), 6.60 (s, 1H), 6.86 (s, 1H), 6.92 (t, J = 7.5 Hz, 1H), 7.01 (d, J = 8.1 Hz, 1H) , 7.17-7.27 (m, 3H), 7.68 (d, J = 8.4 Hz, 1H), 7.85 (br s, 1H), 8.39 (d, J = 7.8 Hz, 1H)

Example 20: 4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine-1- Il] -2- (2-morpholin-4-yl-ethylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 2.25 (s, 3H), 2.38-2.42 (m, 2H), 2.53-2.56 (m, 2H), 2.90 (t, J = 6.6 Hz, 2H), 3.20-3.40 (m, 6H), 3.56-3.59 (m, 4H), 3.73 (s, 3H), 4.53 (s, 2H), 6.52 (d, J = 8.4 Hz, 1H), 6.55 (s, 1H) , 6.87 (s, 1H), 6.90 (t, J = 8.7 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 7.25 (br s, 1H), 7.67 (d, J = 8.4 Hz, 1H ), 7.84 (br s, 1 H), 8.46 (d, J = 4.5 Hz, 1 H)

Example 21 2- (2-Dimethylamino-ethylamino) -4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pi Rolo [3,2-c] pyridin-1-yl] -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 2.17 (s, 6H), 2.25 (s, 3H), 2.45 (t, J = 6.3 Hz, 2H), 2.90 (t, J = 6.3 Hz, 2H) , 3.14-3.42 (m, 4H), 3.73 (s, 3H), 4.53 (s, 2H), 6.51 (d, J = 8.4 Hz, 1H), 6.54 (s, 1H), 6.87 (s, 1H), 6.90 (t, J = 8.7 Hz, 2H), 7.11 (br s, 1H), 7.23 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.4 Hz, 1H), 7.82 (br s, 1H ), 8.34 (t, J = 4.8 Hz, 1H)

Example 22: 4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine-1- Yl] -2- [3- (2-oxo-pyrrolidin-1-yl) -propylamino] -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.69-1.78 (m, 2H), 1.83-1.93 (m, 2H), 2.18 (t, J = 8.1 Hz, 2H), 2.25 (s, 3H), 2.90 (t, J = 6.3 Hz, 2H), 3.10-3.17 (m, 2H), 3.25 (t, J = 6.9 Hz, 2H), 3.29-3.39 (m, 4H), 3.73 (s, 3H), 4.53 (s, 2H), 6.49 (d, J = 9.0 Hz, 1H), 6.53 (s, 1H), 6.87 (s, 1H), 6.90 (d, J = 8.4 Hz, 2H), 7.19 (br s, 1H ), 7.24 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 9.0 Hz, 1H), 7.89 (br s, 1H), 8.40 (t, J = 5.4 Hz, 1H)

Example 23 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [2- (1-oxy-pyrrolidin-1-yl) -ethylamino] -benzamide

¹ H NMR (CDCl ₃ -d ₆ , 300 MHz) δ 0.37-0.42 (m, 2H), 0.48-0.55 (m, 2H), 0.96-1.13 (m, 1H), 1.25 (s, 6H), 1.41 ( s, 4H), 2.43-2.55 (m, 2H), 2.57 (s, 3H), 3.06 (s, 2H), 3.25-3.36 (m, 2H), 3.40 (d, J = 7 Hz, 2H), 3.56 -3.63 (m, 6H), 6.01 (br, 1H), 6.63 (dd, J = 13 and 2 Hz, 1H), 6.95 (d, J = 2 Hz, 1H), 7.50 (d, J = 8 Hz, 1H), 8.40-8.51 (m, 1H)

Example 24 2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2- c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.13-1.39 (m, 4H), 1.20 (s, 6H), 1.78-1.82 (m, 2H), 1.95-1.99 (m, 2H), 2.21 (s , 3H), 2.82 (s, 2H), 3.34-3.51 (m, 2H), 4.58 (d, J = 4.2 Hz, 1H), 6.47 (dd, J = 8.4 and 1.8 Hz, 1H), 6.57 (d, J = 1.8 Hz, 1H), 6.82 (s, 1H), 6.93 (s, 1H), 7.19 (br s, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.86 (br s, 1H), 8.37 (d, J = 7.5 Hz, 1H)

Example 25 2- (4-hydroxycyclohexylamino) -4- (3,5,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d ₆ , 500 MHz) δ 1.16-1.23 (m, 2H), 1.23 (s, 6H), 1.30-1.37 (m, 2H), 1.80-1.82 (m, 2H), 1.97-1.99 (m, 2H), 2.21 (s, 3H), 2.84 (s, 3H), 2.92 (s, 2H), 3.34-3.50 (m, 2H), 4.57 (d, J = 4.0 Hz, 1H), 6.48 ( d, J = 8.5 Hz, 1H), 6.56 (s, 1H), 6.83 (s, 1H), 7.16 (br s, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.85 (br s, 1H ), 8.37 (d, J = 7.5 Hz, 1H)

Example 26: 4- (5-ethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl)- 2- (4-hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.09 (t, J = 6.9 Hz, 3H), 1.15-1.40 (m, 4H), 1.27 (s, 6H), 1.79-1.82 (m, 2H), 1.96-2.00 (m, 2H), 2.22 (s, 3H), 2.92 (s, 2H), 3.40 (q, J = 6.9 Hz, 2H), 3.37-3.50 (m, 2H), 4.56 (d, J = 3.9 Hz, 1H), 6.47 (d, J = 8.1, 1H), 6.56 (s, 1H), 6.82 (s, 1H), 7.16 (br s, 1H), 7.69 (d, J = 8.4 Hz, 1H) , 7.84 (br s, 1 H), 8.37 (d, J = 7.8 Hz, 1 H)

Example 27: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl ) -2- (4-hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.29-0.33 (m, 2H), 0.41-0.46 (m, 2H), 0.94-1.06 (m, 1H), 1.13-1.40 (m, 4H), 1.30 (s, 6H), 1.79-1.83 (m, 2H), 1.96-2.00 (m, 2H), 2.22 (s, 3H), 2.94 (s, 2H), 3.28 (d, J = 6.6 Hz, 2H), 3.33-3.50 (m, 2H), 4.56 (d, J = 3.9 Hz, 1H), 6.48 (d, J = 8.4 Hz, 1H), 6.57 (s, 1H), 6.83 (s, 1H), 7.16 (br s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.84 (br s, 1H), 8.37 (d, J = 7.5 Hz, 1H)

Example 28: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (4-hydroxycyclohexylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.29-0.34 (m, 2H), 0.42-0.48 (m, 2H), 0.98-1.10 (m, 1H), 1.15-1.40 (m, 4H), 1.32 (s, 6H), 1.80-1.84 (m, 2H), 1.98-2.02 (m, 2H), 2.40 (s, 3H), 3.17 (s, 2H), 3.20-3.52 (m, 4H), 4.56 (d , J = 3.9 Hz, 1H), 6.66 (dd, J = 8.4 and 1.8 Hz, 1H), 6.75 (d, J = 1.8 Hz, 1H), 7.20 (br s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.88 (br s, 1H), 8.39 (d, J = 7.5 Hz, 1H)

Example 29: 2- ( Trance -4-hydroxycyclohexylamino) -4- (3- (trifluoromethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4,3-c ] Pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 1.14-1.39 (m, 10H), 1.76-1.83 (m, 2H), 1.96-1.99 (m, 2H), 3.09 (s, 2H), 3.24-3.53 ( m, 2H), 4.58 (d, J = 3.9 Hz, 1H), 6.69 (dd, J = 1.8 and 8.4 Hz, 1H), 6.84 (d, J = 1.8 Hz, 1H), 7.29 (brs, 1H), 7.73 (s, 1 H), 7.76 (d, J = 8.4 Hz, 1 H), 7.95 (brs, 1 H), 8.38 (d, J = 7.8 Hz, 1 H)

Example 30: 2- ( Trance -4-hydroxycyclohexylamino) -4- (3- (trifluoromethyl) -4,5,6,7-tetrahydro-5,6,6-trimethyl-4-oxopyrazolo [4,3 -c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 1.15-1.38 (m, 10H), 1.81 (m, 2H), 1.99 (m, 2H), 2.91 (s, 3H), 3.21 (s, 2H), 3.46 (m, 1H), 3.59 (m, 1H), 4.59 (d, J = 3.9 Hz, 1H), 6.70 (dd, J = 1.8 and 8.4 Hz, 1H), 6.84 (d, J = 1.8 Hz, 1H) , 7.31 (brs, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.97 (brs, 1H), 8.39 (d, J = 7.8 Hz, 1H)

Example 31: 2- ( Trance -4-hydroxycyclohexylamino) -4- (5- (cyclopropylmethyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo Pyrazolo [4,3-c] pyridin-1-yl) benzamide

¹ H-NMR (300 MHz, DMSO-d6) 0.32-0.34 (m, 2H), 0.44-0.47 (m, 2H), 0.99-1.05 (m, 1H), 1.14-1.27 (m, 4H), 1.34 ( s, 6H), 1.81 (d, J = 3.7 Hz, 2H), 1.99 (d, J = 3.7 Hz, 2H), 3.24 (s, 2H), 3.36 (s, 2H), 3.42-3.51 (m, 1H ), 4.57 (d, J = 4.2 Hz, 1H), 6.71 (dd, J = 1.5, 8.4 Hz, 1H), 6.85 (s, 1H), 7.31 (br.s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.96 (br.s, 1H), 8.39 (d, J = 7.8 Hz, 1H)

Example 32: 2- ( Trance -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4,3-c] Pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 0.22 (m, 2H), 0.39 (m, 2H), 1.14-1.39 (m, 11H), 1.82 (m, 2H), 1.99 (m, 2H), 2.73 (d, J = 6.9 Hz, 2H), 3.05 (s, 2H), 3.30-3.52 (m, 2H), 4.58 (d, J = 4.2 Hz, 1H), 6.66 (dd, J = 1.8 and 8.4 Hz, 1H), 6.76 (d, J = 1.8 Hz, 1H), 7.23 (brs, 1H), 7.32 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.90 (brs, 1H), 8.39 ( d, J = 7.5 Hz, 1H).

Example 33: 2- ( Trance -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -4,5,6,7-tetrahydro-5,6,6-trimethyl-4-oxopyrazolo [4,3- c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 0.21 (m, 2H), 0.39 (m, 2H), 1.15-1.39 (m, 11H), 1.82 (d, J = 10.8 Hz, 2H), 1.99 (d , J = 10.5 Hz, 2H), 2.74 (d, J = 6.9 Hz, 2H), 2.87 (s, 3H), 3.17 (s, 2H), 3.29-3.52 (m, 2H), 4.59 (d, J = 4.2 Hz, 1H), 6.67 (dd, J = 1.5 and 8.4 Hz, 1H), 6.76 (s, 1H), 7.22 (brs, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.89 (brs, 1H), 8.40 (d, J = 7.5 Hz, 1H).

Example 34: 2- ( Trance -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -5-ethyl-4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4, 3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 0.21 (m, 2H), 0.39 (m, 2H), 1.11 (t, d = 6.9 Hz, 3H), 1.19-1.39 (m, 11H), 1.82 (d , J = 10.2 Hz, 2H), 2.00 (d, J = 8.7 Hz, 2H), 2.74 (d, J = 6.9 Hz, 2H), 3.16 (d, J = 2.4 Hz, 2H), 3.29-3.52 (m , 4H), 4.59 (d, J = 4.2 Hz, 1H), 6.67 (d, J = 8.4 Hz, 1H), 6.75 (s, 1H), 7.22 (brs, 1H), 7.72 (d, J = 8.4 Hz , 1H), 7.89 (brs, 1H), 8.39 (d, J = 7.5 Hz, 1H).

Example 35: 2- ( Trance -4-hydroxycyclohexylamino) -4- (4,5,6,7-tetrahydro-3-isobutyl-6,6-dimethyl-4-oxopyrazolo [4,3-c] pyridine-1 Benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 0.91 (d, J = 6.6 Hz, 6H), 1.15-1.34 (m, 10H), 1.82 (d, J = 9.6 Hz, 2H), 1.99 (d, J = 10.8 Hz, 2H), 2.09 (m, 1H), 2.71 (d, J = 6.9 Hz, 2H), 3.04 (s, 2H), 3.27-3.51 (m, 2H), 4.59 (d, J = 4.2 Hz , 1H), 6.65 (dd, J = 1.8 and 8.4 Hz, 1H), 6.75 (d, J = 1.5 Hz, 1H), 7.22 (brs, 1H), 7.28 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.89 (brs, 1H), 8.38 (d, J = 7.5 Hz, 1H).

Example 36: 2- ( Trance -4-hydroxycyclohexylamino) -4- (3,5-bis (cyclopropylmethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4,3 -c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 0.19-0.47 (m, 8H), 1.02 (m, 1H), 1.11-1.39 (m, 11H), 1.82 (d, J = 10.2 Hz, 2H), 2.00 (d, J = 9.6 Hz, 2H), 2.75 (d, J = 6.9 Hz, 2H), 3.18 (s, 2H), 3.28-3.52 (m, 4H), 4.57 (d, J = 4.2 Hz, 1H) , 6.68 (d, J = 8.4 Hz, 1H), 6.76 (s, 1H), 7.21 (brs, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.89 (brs, 1H), 8.39 (d, J = 7.5 Hz, 1H).

Example 37: 2- ( Trance -4-hydroxycyclohexylamino) -4- (5-allyl-4,5,6,7-tetrahydro-3-isobutyl-6,6-dimethyl-4-oxopyrazolo [4,3-c ] Pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) δ 0.91 (d, J = 6.9 Hz, 6H), 1.15-1.39 (m, 10H), 1.82 (d, J = 9.9 Hz, 2H), 2.00 (d, J = 9.0 Hz, 2H), 2.08 (m, 1H), 2.71 (d, J = 7.2 Hz, 2H), 3.17 (s, 2H), 3.27-3.51 (m, 2H), 4.08 (m, 2H), 4.58 (d, J = 4.2 Hz, 1H), 5.08 (d, J = 10.2 Hz, 1H), 5.21 (d, J = 17.1 Hz, 1H), 5.83 (m, 1H), 6.67 (d, J = 8.4 Hz , 1H), 6.75 (s, 1H), 7.22 (brs, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.89 (brs, 1H), 8.39 (d, J = 7.5 Hz, 1H).

Example 38: 4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (2-morpholin-4-yl-ethylamino) -benzamide

¹ H-NMR (300 MHz, CDCl 3) δ 1.38 (s, 6H), 2.054-2.51 (m, 4H), 2.62 (s, 1H), 2.70 (t, J = 6.3 Hz, 2H), 3.00 (s, 2H), 3.29 (q, J = 6.3, 11.1 Hz, 2H), 3.76 (t, J = 4.5 Hz, 4H), 5.44 (s, 1H), 5.73 (brs, 1H), 6.58 (dd, J = 2.1 , 8.4 Hz, 1H), 6.80 (d, J = 2.1 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 8.26 (t, J = 4.8 Hz, 1H)

Example 39: 2- [3- (2-oxo-pyrrolidin-1-yl) -propylamino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide

¹ H-NMR (300 MHz, CDCl 3) δ 1.32 (s, 6H), 1.87-1.96 (m, 2H), 2.00-2.05 (m, 4H), 2.41-2.63 (m, 5H), 2.81 (s, 2H ), 3.20 (q, J = 6.6, 12.3 Hz, 2H), 3.39-3.45 (m, 4H), 5.01 (s, 1H), 5.68 (brs, 1H), 6.43 (dd, J = 2.1, 8.4 Hz, 1H), 6.49 (d, J = 2.1 Hz, 1H), 6.61 (s, 1H), 7.44 (d, J = 8.4 Hz, 1H), 8.06 (t, J = 5.1 Hz, 1H)

Example 40: 4- (5-ethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine- 1-yl) -2- (4-hydroxy-cyclohexylamino) -benzamide

¹ H-NMR (300 MHz, CDCl 3) δ 1.15 (t, J = 6.9 Hz, 3H), 1.31 (s, 6H), 1.91-1.95 (m, 2H), 2.00-2.40 (m, 2H), 2.48- 2.50 (m, 1H), 3.09 (d, J = 4.2 Hz, 1H), 3.22-3.24 (m, 1H), 3.47 (q, J = 6.9, 14.1 Hz, 2H), 3.55-3.61 (m, 1H) , 6.49 (dd, J = 2.1, 8.4 Hz, 1H), 6.61 (d, J = 2.1 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 7.5 Hz, 1H) , 9.66 (s, 1H)

Example 41: 4- (5-cyclopropylmethyl-3-isobutyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine- 1-yl) -2- (4-hydroxy-cyclohexylamino) -benzamide

¹ H-NMR (300 MHz, DMSO-d6) δ 0.13-0.14 (m, 2H), 0.23-0.26 (m, 2H), 0.49 (s, 3H), 0.51 (s, 3H), 1.18 (s, 6H ), 1.58-1.62 (m, 2H), 1.74-1.78 (m, 2H), 2. 68 (s, 2H), 2.77 (d, J = 7.2 Hz, 2H), 3.15-3.18 (m, 2H), 3.22-3.32 (m, 1H), 4.37 (d, J = 4.2 Hz, 1H), 6.38 (dd, J = 1.8., 8.4 Hz, 1H), 6.57 (d, J = 1.8 Hz, 1H), 7.06 ( brs, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.73 (brs, 1H), 8.14 (d, J = 8.7 Hz, 1H)

Example 42: 4- (5-cyclopropylmethyl-3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1 -Yl) -2- (4-hydroxycyclohexylamino) -benzamide

¹ H-NMR (300 MHz, DMSO-d6) δ 0.12-0.14 (m, 2H), 0.24-0.26 (m, 2H), 1.03 (t, J = 7.2 Hz, 3H), 1.13 (s, 6H), 1.61-1.66 (m, 2H), 1.79-1.84 (m, 2H), 2.64 (q, J = 7.5, 15 Hz, 2H), 2.98 (s, 2H), 3.25-3.33 (m, 1H), 4.38 (d , J = 3.9 Hz, 1H), 6.48 (dd, J = 1.8, 8.7 Hz, 1H), 6.55 (m, 1H), 7.02 (brs, 1H), 7.53 (d, J = 8.7 Hz, 1H), 7.69 (brs, 1H), 8.20 (d, J = 7.8 Hz, 1H)

Example 43: 4- (3,5-bis-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1 -Yl) -2- (2-morpholin-4-yl-ethylamino) -benzamide

¹ H-NMR (300 MHz, DMSO-d6) δ 0.34-0.39 (m, 2H), 0.47-0.50 (m, 2H), 0.52-0.55 (m, 2H), 0.58-0.62 (m, 2H), 2.90 (d, 6.9 Hz, 2H), 3.02 (d, J = 11.1 Hz, 2H), 3.54 (m, 2H), 3.78-3.82 (m, 2H), 3.92-3.97 (m, 2H), 4.32 (t, J = 10.5 Hz, 2H), 6.93 (dd, J = 1.8, 8.4 Hz, 1H), 7.22 (s, 1H), 7.42 (brs, 1H), 7.90 (d, J = 8.4 Hz, 1H), 8.06 ( brs, 1H), 8.77 (t, J = 5.7 Hz, 1H)

Example 44: 2- (4-hydroxycyclohexylamino) -4- [3,6,6-trimethyl-5- (2-methyl-allyl) -4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl] -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 1.11-1.39 (m, 10H), 1.71 (s, 3H), 1.77-1.87 (m, 2H), 1.93-2.07 (m, 2H), 2.40 (s , 3H), 2.72 (br, 1H), 3.19 (s, 2H), 3.41-3.53 (br, 1H), 3.99 (s, 2H), 4.81 (d, J = 15 Hz, 2H), 6.61-6.71 ( m, 1H), 6.75 (br, 1H), 7.16-7.30 (m, 1H), 7.72 (d, J = 8 Hz, 1H), 7.82-7.95 (m, 1H), 8.40 (d, J = 8 Hz , 1H)

Example 45 2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl ₃ -d ₆ , 300 MHz) δ 1.17-1.33 (m, 4H), 1.37 (s, 6H), 1.72-1.88 (m, 2H), 1.94-2.10 (m, 2H), 2.58 ( s, 3H), 2.98 (s, 2H), 6.78 (d, J = 3.0 Hz, 1H), 7.44 (s, 1H), 7.47 (s, 1H), 7.61 (s, 1H)

Example 46: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (2-morpholin-4-yl-ethylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.31-0.33 (m, 2H), 0.43-0.46 (m, 2H), 0.98-1.06 (m, 1H), 1.24 (s, 2H), 1.33 (s , 6H), 1.53 (1H), 2.27-2.29 (m, 2H), 2.39-2.47 (m, 4H), 2.73-2.74 (m, 2H), 3.18 (s, 3H), 3.51 (s, 2H), 3.60 (t, 4H, J = 9 Hz), 6.67 (dd, 1H, J = 10 and 2 Hz), 6.77 (d, 1H, 2.1 Hz), 7.16-7.27 (m, 1H), 7.71 (d, 1H , 9 Hz) 7.85-7.88 (m, 1H), 8.49 (s, 1H)

Example 47 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [3- (2-oxo-pyrrolidin-1-yl) -propylamino] -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.31-0.32 (m, 2H), 0.41-0.45 (m, 2H), 0.99-1.04 (m, 1H), 1.32 (s, 6H), 1.75-1.79 (m, 2H), 1.88-1.93 (m, 2H), 2.20 (t, 2H, J = 16), 2.40 (s, 3H), 2.50 (s, 2H), 3.11-3.20 (m, 4H), 3.25 -3.38 (m, 4H), 6.67 (dd, 1H, J = 10 and 2), 7.23-7.30 (m, 1H), 7.73 (d, 1H, J = 8), 7.87-7.98 (m, 1H), 8.38-8.46 (m, 1H)

Example 48: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (2-dimethylamino-ethylamino) -benzamide

¹ H NMR (DMSO-d ₆ , 300 MHz) δ 0.31-0.34 (m, 2H), 0.43-0.47 (m, 2H), 0.93-1.09 (m, 1H), 1.32 (s, 6H), 2.19 (s , 6H), 2.27 (t, 2H, J = 2 Hz), 2.40 (s, 3H), 2.71-2.75 (m, 2H), 3.12-3.24 (m, 2H), 4.08-4.13 (m, 2H), 4.45-4.50 (m, 1H), 6.65-6.68 (m, 1H), 6.74 (d, 1H, J = 2 Hz), 7.11-7.25 (m, 1H), 7.71 (d, 1H, J = 8), 7.84-7.89 (m, 1 H), 8.31-8.40 (m, 1 H)

Example 49: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (2-pyrrolidin-1-yl-ethylamino) -benzamide

¹ H NMR (CDCl ₃ -d ₆ , 300 MHz) δ 0.37-0.42 (m, 2H), 0.50-0.56 (m, 2H), 0.99-1.15 (m, 1H), 1.25 (s, 2H), 1.40 ( s, 6H), 1.75-1.87 (m, 4H), 2.17 (s, 2H), 2.57 (s, 3H), 2.54-2.64 (m, 4H), 3.04 (s, 2H), 3.32-3.38 (m, 2H), 3.40 (d, J = 7, 2H), 3.64 (s, 2H), 3.74 (s, 1H), 5.67 (br, 1H), 6.62 (dd, J = 10 and 2 Hz), 6.80 (d , J = 2, 1H), 8.10-8.13 (m, 1H), 7.46 (d, J = 8, 1H)

Example 50 Amino Acetic Acid 4- [2-carbamoyl-5- (3,5,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2- c] pyridin-1-yl) -phenylamino] -cyclohexyl ester

¹ H NMR (DMSO-d ₆ , 300 MHz) d 1.22 (s, 6H), 1.26-1.38 (m, 2H), 1.48-1.61 (m, 2H), 1.89-1.95 (m, 2H), 2.02-2.10 (m, 2H), 2.21 (s, 3H), 2.84 (s, 3H), 2.93 (s, 2H), 3.24 (s, 2H), 3.45-3.51 (m, 3H), 4.67-4.76 (m, 1H ), 6.50 (d, J = 8.1 Hz, 1H), 6.60 (s, 1H), 6.83 (s, 1H), 7.20 (br s, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.88 ( br s, 1 H), 8.44 (d, J = 7.8 Hz, 1 H)

Example 51 Amino Acetic Acid 4- [2-carbamoyl-5- (3,5,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2- c] pyridin-1-yl) -phenylamino] -cyclohexyl ester methanesulphonic acid

¹ H NMR (DMSO-d ₆ , 300 MHz) d 1.22 (s, 6H), 1.31-1.42 (m, 2H), 1.56-1.66 (m, 2H), 1.93-2.07 (m, 4H), 2.21 (s , 3H), 2.33 (s, 4H), 2.84 (s, 3H), 2.94 (s, 2H), 3.46-3.57 (m, 1H), 3.78-3.84 (m, 2H), 4.81-4.88 (m, 1H ), 6.51 (d, J = 8.1 Hz, 1H), 6.61 (s, 1H), 6.84 (s, 1H), 7.21 (br s, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.89 ( br s, 1 H), 8.18 (s, 3 H)

Example 52: 2- (1-acetylpiperidin-4-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl -4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.32 (s, 6H), 1.69 (m, 2H), 1.96 (m, 2H), 2.01 (s, 3H), 2.40 (s, 3H), 2.94 (m, 1H), 3.17 (s, 2H), 3.70-3.82 (m, 4H), 4.11 (m, 1H), 5.37 (dd , J = 2.1 and 6.0 Hz, 1H), 6.69 (d, J = 8.4Hz, 1H), 6.82 (s, 1H), 7.25 (brs, 1H), 7.75 (d, J = 8.4Hz, 1H), 7.93 (brs, 1H), 8.54 (d, J = 7.8 Hz, 1H).

Example 53 (S) -tert-butyl 3- (2-carbamoyl-5- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl-4 Oxopyrazole [4,3-c] pyridin-1-yl) phenylamino) pyrrolidine-1-carboxylate

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.32 (s, 3H), 1.33 (s, 3H), 1.39 (s, 9H), 1.69 (m, 2H), 1.84 (m, 1H), 2.18 (m, 1H), 2.41 (s, 3H), 3.12 (m, 1H), 3.18 (d, J = 3.9 Hz, 2H), 3.31 (s, 2H), 3.60 (m, 1H), 4.14 (m, 1H), 6.74 (d, J = 8.4 Hz, 1H), 6.79 (s, 1H), 7.29 (brs, 1H), 7.77 (d , J = 8.7 Hz, 1H), 7.96 (brs, 1H), 8.65 (brs, 1H).

Example 54: 2-((S) -1-acetylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6 , 6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.23 (d, J = 1.8 Hz, 3H), 1.33 (s, 3H) , 1.75-1.99 (m, 1H), 1.95 (d, J = 5.1 Hz, 3H), 2.23 (m, 1H), 2.41 (s, 3H), 3.21 (m, 2H), 3.24-3.33 (m, 3H ), 3.40 (m, 1H), 3.51-3.88 (m, 2H), 4.18 (m, 1H), 6.75 (m, 1H), 6.80 (m, 1H), 7.28 (brs, 1H), 7.77 (d, J = 8.4 Hz, 1 H), 7.95 (brs, 1 H), 8.65 (dd, J = 6.9 and 15.6 Hz, 1 H).

Example 55: 2-((S) -1-benzoylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6 , 6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.01 (m, 1H), 1.23 (d, J = 12.0 Hz, 3H), 1.33 (d, J = 5.4 Hz, 3H), 1.93 (m, 1H), 2.27 (m, 1H), 2.39 (d, J = 13.5 Hz, 3H), 3.07 (m, 1H), 3.24 (d, J = 24.9 Hz, 2H) , 3.31 (d, J = 7.2Hz, 2H), 3.52 (m, 1H), 3.62 (m, 1H), 3.83 (m, 1H), 4.22 (m, 1H), 6.69-6.73 (m, 2H), 7.32 (brs, 1H), 7.40-7.51 (m, 5H), 7.77 (dd, J = 8.7 and 12.3 Hz, 1H), 7.96 (brs, 1H), 8.70 (dd, J = 6.6 and 12.0 Hz, 1H) .

Example 56: 2-((S) -1-phenylsulfonylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3, 6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.32 (d, J = 8.4 Hz, 6H), 1.73 (m, 2H) , 2.11 (m, 1H), 2.41 (s, 3H), 3.05 (m, 1H), 3.15 (d, J = 6.3Hz, 2H), 3.27-3.34 (m, 3H), 3.50 (m, 1H), 4.05 (m, 1H), 6.67 (s, 1H), 6.74 (dd, J = 1.8 and 8.4 Hz, 1H), 7.25 (brs, 1H), 7.56-7.61 (m, 2H), 7.66-7.79 (m, 4H), 7.93 (brs, 1 H), 8.53 (d, J = 6.6 Hz, 1 H).

Example 57: 2-((S) -1-cyclopropylcarbonylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3 , 6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 0.73 (m, 4H), 1.02 (m, 1H), 1.32 (s, 6H), 1.62-1.88 ( m, 2H), 1.97 (m, 1H), 2.41 (s, 3H), 3.20 (d, J = 9.6 Hz, 2H), 3.32 (s, 2H), 3.41-3.67 (m, 2H), 3.71-4.06 (m, 2H), 4.13-4.31 (m, 1H), 6.82 (dd, J = 1.8 and 5.1 Hz, 1H), 6.87 (s, 1H), 7.28 (brs, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.96 (brs, 1H), 8.68 (dd, J = 6.6, 17.4 Hz, 1H).

Example 58: 2-((S) -1- (2-tert-butyloxycarbonylaminoacetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5 , 6,7-tetrahydro-3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.30-1.38 (m, 15H), 1.75-2.00 (m, 1H), 2.24 (m, 1H), 2.41 (s, 3H), 3.20 (m, 2H), 3.27 (m, 1H), 3.32 (s, 2H), 3.44 (m, 1H), 3.55 (m, 1H), 3.65 -3.88 (m, 3H), 4.19 (m, 1H), 6.76 (m, 3H), 7.27 (brs, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.96 (brs, 1H), 8.65 ( dd, J = 6.6 and 14.4 Hz, 1 H).

Example 59: 2 -((S) -1- (2-aminoacetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetra Hydro-3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide hydrochloride

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.45 (m, 2H), 1.01 (m, 1H), 1.33 (s, 6H), 1.80-2.05 (m, 1H), 2.27 ( m, 1H), 2.41 (s, 3H), 3.20 (m, 2H), 3.32 (d, J = 6.3 Hz, 2H), 3.38-3.59 (m, 3H), 3.70-3.87 (m, 3H), 4.19 -4.29 (m, 1H), 6.75 (m, 1H), 6.81 (s, 1H), 7.28 (brs, 1H), 7.79 (d, J = 8.4 Hz, 1H), 8.00 (brs, 1H), 8.13 ( brs, 3 H), 8.69 (brs, 1 H).

Example 60: 2-((S) -1- (2- (dimethylamino) acetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6, 7-tetrahydro-3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.32 (s, 3H), 1.34 (s, 3H), 1.75-1.99 ( m, 1H), 2.17 (s, 3H), 2.18 (s, 2H), 2.20 (s, 3H), 2.15-2.23 (m, 1H), 2.41 (s, 3H), 2.95-3.08 (m, 2H) , 3.19 (m, 1H), 3.29 (s, 2H), 3.43 (m, 1H), 3.60-3.88 (m, 2H), 4.17 (m, 1H), 6.47 (m, 1H), 6.81 (s, 1H ), 7.28 (brs, 1 H), 7.77 (d, J = 8.4 Hz, 1 H), 7.95 (brs, 1 H), 8.64 (dd, J = 7.2 and 10.5 Hz, 1 H).

Example 61 5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2 -[1- (2-Diethylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 0.89 (t, J = 7.2 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H), 1.01 (m, 1H), 1.32 (s, 6H), 1.75-1.99 (m, 1H), 2.13-2.28 (m, 1H), 2.18 (s, 2H), 2.40 (d, J = 1.5 Hz, 3H), 2.46-2.55 (m, 4H), 3.06-3.23 (m, 2H), 3.30 (s, 2H), 3.26-3.62 (m, 2H), 3.65-3.94 (m, 2H), 4.16 (m, 1H), 6.73 (dd, J = 1.8 and 8.4 Hz, 1 H), 6.81 (dd, J = 1.8 and 4.8 Hz, 1 H), 7.28 (brs, 1 H), 7.76 (d, J = 8.7 Hz, 1 H), 7.95 (brs , 1H), 8.65 (dd, J = 6.9 and 10.5 Hz, 1H).

Example 62: 2- [1- (2-cyclopropylamino-acetyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo -4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.21 (m, 2H), 0.32 (m, 4H), 0.44 (m, 2H), 1.02 (m, 1H), 1.33 (m, 6H), 1.78-1.99 ( m, 1H), 2.09-2.33 (m, 2H), 2.41 (s, 3H), 3.20 (dd, J = 4.2 and 11.4 Hz, 2H), 3.25 (m, 1H), 3.03-3.31 (m, 4H) , 3.43-3.58 (m, 2H), 3.65-3.85 (m, 1H), 4.18 (m, 1H), 6.77 (m, 2H), 7.29 (brs, 1H), 7.77 (d, J = 8.4Hz, 1H ), 7.97 (brs, 1 H), 8.66 (dd, J = 6.6 and 14.7 Hz, 1 H).

Example 63: 2- (1-acetyl-pyrrolidin-3-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7 -Tetrahydro-pyrazolo4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.23 (d, J = 1.8 Hz, 3H), 1.33 (s, 3H) , 1.75-1.99 (m, 1H), 1.95 (d, J = 5.1 Hz, 3H), 2.23 (m, 1H), 2.41 (s, 3H), 3.21 (m, 2H), 3.24-3.33 (m, 3H ), 3.40 (m, 1H), 3.51-3.88 (m, 2H), 4.18 (m, 1H), 6.75 (m, 1H), 6.80 (m, 1H), 7.28 (brs, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.95 (brs, 1H), 8.65 (dd, J = 6.9 and 15.6 Hz, 1H).

Example 64: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-methanesulfonyl-pyrrolidin-3-yl-amino) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.32 (d, J = 2.4 Hz, 6H), 1.91 (m, 1H) , 2.28 (m, 1H), 2.41 (s, 3H), 2.92 (s, 3H), 3.11 (dd, J = 3.9 and 10.5 Hz, 1H), 3.19 (d, J = 1.8 Hz, 2H), 3.29- 3.39 (m, 4H), 3.63 (dd, J = 5.7 and 10.2Hz, 1H), 4.22 (m, 1H), 6.76 (d, J = 8.4Hz, 1H), 6.79 (s, 1H), 7.32 (brs , 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.97 (brs, 1H), 8.68 (d, J = 6.9 Hz, 1H).

Example 65: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (3-Methyl-butyryl) -pyrrolidin-3-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.34 (m, 2H), 0.44 (m, 2H), 0.89 (m, 6H), 1.02 (m, 1H), 1.33 (m, 6H), 1.79-2.31 ( m, 5H), 2.41 (s, 3H), 3.20 (m, 2H), 3.23-3.32 (m, 3H), 3.43 (m, 1H), 3.51-3.86 (m, 2H), 4.17 (m, 1H) , 6.76 (m, 2H), 7.28 (brs, 1H), 7.77 (d, J = 9.6 Hz, 1H), 7.95 (brs, 1H), 8.65 (dd, J = 6.6 and 15.9 Hz, 1H).

Example 66: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-ethylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.34 (m, 2H), 0.44 (m, 2H), 1.00 (m, 4H), 1.32 (m, 6H), 1.79-1.97 (m, 1H), 2.16- 2.29 (m, 1H), 2.41 (s, 3H), 2.54 (m, 2H), 3.18-3.31 (m, 7H), 3.50 (m, 2H), 3.65-3.85 (m, 1H), 4.18 (m, 1H), 6.64 (s, 1H), 6.77 (m, 2H), 7.28 (brs, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.96 (brs, 1H), 8.65 (dd, J = 6.9 and 14.7 Hz, 1 H).

Example 67 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-isobutylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 0.85 (m, 6H), 1.02 (m, 1H), 1.33 (m, 6H), 1.64 (m, 1H), 1.76-1.99 (m, 1H), 2.13-2.33 (m, 3H), 2.41 (s, 3H), 3.18-3.32 (m, 7H), 3.50 (m, 2H), 3.65-3.85 (m, 1H), 4.18 (m, 1H), 6.79 (m, 2H), 7.28 (brs, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.96 (brs, 1H), 8.65 (dd, J = 6.6 and 14.7 Hz, 1 H).

Example 68: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-piperidin-1-yl-acetyl) -pyrrolidin-3-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.34 (m, 11H), 1.49 (m, 2H), 1.76-1.98 ( m, 1H), 2.11-2.40 (m, 7H), 2.93-3.32 (m, 7H), 3.43 (m, 1H), 3.54-3.90 (m, 2H), 4.16 (m, 1H), 6.80 (m, 2H), 7.26 (brs, 1H), 7.77 (d, J = 8.7 Hz, 1H), 7.94 (brs, 1H), 8.65 (dd, J = 7.2 and 13.8 Hz, 1H).

Example 69: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-morpholin-4-yl-acetyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.33 (d, J = 3.6 Hz, 2H), 0.45 (d, J = 6.3 Hz, 2H), 1.02 (m, 1H), 1.16-1.43 (m, 8H ), 2.00 (s, 3H), 2.41 (s, 6H), 2.95-3.25 (m, 5H), 3.58 (s, 3H), 3.73 (m, 1H), 3.94 (d, J = 12.3 Hz, 1H) , 4.03-4.12 (m, 1H), 6.70 (d, J = 7.8 Hz, 1H), 6.84 (s, 1H), 7.26 (br.s, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.94 (br.s, 1H), 8.55 (d, J = 6.9 Hz, 1H)

Example 70: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-isopropylamino-acetyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.32 (m, 2H), 0.44 (m, 2H), 0.98 (s, 6H), 1.32 (s, 6H), 2.00 (s, 2H), 2.40 (s , 3H), 2.68 (s, 1H), 2.99 (m, 1H), 3.18 (m, 2H), 3.36 (m, 4H), 3.74 (s, 2H), 4.13 (d, J = 8.7Hz, 1H) , 6.70 (d, J = 5.1Hz, 1H), 6.83 (s, 1H), 7.25 (br.s, 1H), 7.75 (d, J = 7.8Hz, 1H), 7.94 (br.s, 1H), 8.55 (d, J = 6.6 Hz, 1H)

Example 71: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-Pyrrolidin-1-yl-acetyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.32 (d, J = 3.6 Hz, 2H), 0.44 (d, J = 6.3 Hz, 2H), 1.02 (m, 1H), 1.32 (s, 6H), 1.68 (m, 4H), 1.98 (m, 4H), 2.40 (s, 3H), 2.97 (t, J = 15.9, 22.2 Hz, 1H), 3.18 (s, 2H), 3.23 (s, 1H), 3.70 (br.s, 1H), 3.90 (d, J = 15Hz, 1H), 4.10 (d, J = 15Hz, 1H), 6.69 (d, J = 7.8Hz, 1H), 6.82 (s, 1H), 7.24 (br.s, 1H), 7.75 (d, J = 7.8Hz, 1H), 7.92 (br.s, 1H), 8.54 (d, J = 6.9Hz, 1H)

Example 72: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-ethanesulfonyl-pyrrolidin-3-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.04 (m, 1H), 1.37 (t, J = 7.2 Hz, 3H), 1.42 (s, 3H), 1.43 (s, 3H), 2.08 (m, 1H), 2.35 (m, 1H), 2.57 (s, 3H), 2.96-3.10 (m, 4H), 3.34 (dd, J = 3.9 and 10.5Hz, 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.59 (m, 2H), 3.80 (dd, J = 5.7 and 10.5 Hz, 1H), 4.21 (m, 1H), 5.75 (brs, 2H), 6.63 (dd , J = 2.1 and 8.4 Hz, 1H), 6.82 (d, J = 2.1 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 8.39 (d, J = 6.3 Hz, 1H).

Example 73: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-dimethylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.05 (m, 1H), 1.42 (s, 6H), 2.05 (m, 1H), 2.35 (m, 1H) , 2.57 (s, 3H), 2.83 (s, 6H), 3.04 (s, 2H), 3.28 (dd, J = 4.2 and 10.2 Hz, 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.51 ( t, J = 6.9 Hz, 2H), 3.73 (dd, J = 5.7 and 9.9 Hz, 1H), 4.19 (m, 1H), 5.76 (brs, 2H), 6.63 (dd, J = 2.1 and 8.4 Hz, 1H ), 6.80 (d, J = 1.8 Hz, 1H), 7.49 (d, J = 8.7 Hz, 1H), 8.39 (d, J = 6.6 Hz, 1H).

Example 74: 2- [1- (Boc-sulfamoyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.39 (m, 2H), 0.52 (m, 2H), 1.05 (m, 1H), 1.37 (s, 3H), 1.44 (s, 9H), 1.45 (s, 3H) , 2.08 (m, 1H), 2.34 (m, 1H), 2.57 (s, 3H), 2.97 (d, J = 16.5 Hz, 1H), 3.17 (d, J = 16.2 Hz, 1H), 3.34 (m, 1H), 3.40 (d, J = 6.6 Hz, 2H), 3.59 (m, 1H), 3.71 (m, 1H), 4.11 (m, 2H), 5.87 (brs, 2H), 6.65 (dd, J = 1.8 and 8.4 Hz, 1 H), 6.69 (d, J = 1.8 Hz, 1 H), 7.47 (d, J = 8.4 Hz, 1 H), 8.34 (d, J = 5.7 Hz, 1 H).

Example 75: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (propane-2-sulfonyl) -pyrrolidin-3-yl-amino] -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.06 (m, 1H), 1.37 (dd, J = 2.7 and 6.9 Hz, 6H), 1.42 (s, 6H) , 2.06 (m, 1H), 2.36 (m, 1H), 2.57 (s, 3H), 3.04 (s, 2H), 3.23 (m, 1H), 3.33 (dd, J = 4.2 and 10.2Hz, 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.61 (m, 2H), 3.86 (dd, J = 5.7 and 10.2 Hz, 1H), 4.20 (m, 1H), 5.76 (brs, 2H), 6.64 (dd , J = 1.8 and 8.4Hz, 1H ), 6.81 (d, J = 1.8Hz, 1H), 7.49 (d, J = 8.4Hz, 1H), 8.40 (d, J = 6.6Hz, 1H).

Example 76: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-sulfamoyl-pyrrolidin-3-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.05 (m, 1H), 1.39 (s, 3H), 1.42 (s, 3H), 2.07 (m, 1H) , 2.29 (m, 1H), 2.57 (s, 3H), 3.01 (d, J = 2.7 Hz, 2H), 3.34 (dd, J = 2.4 and 10.8 Hz, 1H), 3.40 (d, J = 6.6 Hz, 2H), 3.47 (m, 2H), 3.69 (dd, J = 5.4 and 10.8 Hz, 1H), 4.17 (m, 1H), 5.23 (s, 2H), 6.23 (brs, 2H), 6.51 (dd, J = 1.8 and 8.4 Hz, 1H), 6.69 (d, J = 1.8 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 6.6 Hz, 1H).

Example 77 2-Bromo-4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ): 7.79-7.85 (m, 2H), 7.44-7.47 (m, 1H), 6.21 (br, 1H), 5.83 (br, 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.03 (s, 2H), 2.57 (s, 3H), 1.42 (s, 6H), 1.03-1.08 (m, 1H), 0.50-0.54 (m, 2H), 0.39-0.43 (m, 2H)

Example 78: 2- [1- (2-cyclobutylamino-acetyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo -4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.31 (d, J = 3.6 Hz, 2H), 0.44 (d, J = 6.3 Hz, 2H), 0.86 (m, 1H), 1.01 (m, 2H), 1.23 (m, 2H), 1.32 (m, 6H), 1.48-1.68 (m, 4H), 1.95-2.07 (m, 4H), 2.40 (s, 3H), 2.98 (t, J = 12.3, 23.7 Hz, 1H), 3.18 (m, 4H), 3.29 (s, 3H), 3.72 (d, J = 13.5 Hz, 2H), 4.12 (d, J = 12.6 Hz, 1H), 6.68 (d, J = 7.8 Hz, 1H), 6.82 (s, 1H), 7.25 (br.s, 1H), 7.75 (d, J = 7.8Hz, 1H), 7.92 (br.s, 1H), 8.55 (d, J = 6.9Hz, 1H )

Example 79: 2- (1-Carbamoylmethyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6 , 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.42 (m, 2H), 0.54 (m, 2H), 1.12 (m, 1H), 1.40 (s, 6H), 2.35 (m, 2H), 2.49 (m, 2H) , 2.57 (s, 3H), 2.87 (m, 2H), 3.62 (s, 2H), 3.04 (s, 2H), 3.42 (d, J = 6.7 Hz, 2H), 3.52 (m, 1H), 5.43 ( brs, 1H), 5.67 (brs, 2H), 6.55 (dd, J = 8.4 Hz, J = 1.8 Hz, 1H), 6.81 (d, J = 1.8 Hz, 1H), 7.06 (brs, 1H), 7.48 ( d, J = 8.4 Hz, 1H), 8.24 (d, J = 7.50 Hz, 1H)

Example 80: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-oxo-propyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.41 (m, 2H), 0.57 (m, 2H), 1.07 (m, 1H), 1.41 (s, 6H), 1.74 (m, 2H), 2.05 (m, 2H) , 2.17 (s, 3H), 2.38 (m, 2H), 2.58 (s, 3H), 2.79 (m, 2H), 3.02 (s, 2H), 3.22 (s, 2H), 3.46 (d, J = 6.7 Hz, 2H), 3.42 (m, 1H), 5.64 (brs, 2H), 6.57 (dd, J = 8.5Hz, J = 1.9Hz, 1H), 6.80 (d, J = 1.9Hz, 1H), 7.48 ( d, J = 8.5Hz, 1H) , 8.25 (d, J = 7.4Hz, 1H)

Example 81: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-oxo-2-phenyl-ethyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.40 (m, 2H), 0.51 (m, 2H), 0.88 (m, 1H), 1.40 (s, 6H), 1.69 (m, 2H), 2.09 (m, 2H) , 2.48 (m, 2H), 2.57 (s, 3H), 2.89 (m, 2H), 3.01 (s, 2H), 3.39 (d, J = 6.7 Hz, 2H), 3.48 (m, 1H), 3.85 ( s, 2H), 5.69 (brs, 2H), 6.53 (dd, J = 8.4Hz, J = 2.0Hz, 1H), 6.78 (d, J = 2.0Hz, 1H), 7.43 (m, 3H), 7.57 ( m, 1H), 8.02 (m, 2H), 8.22 (d, J = 7.50Hz, 1H)

Example 82: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-formyl-piperidin-4-yl-amino) -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.37 (m, 2H), 0.56 (m, 2H), 0.88 (m, 1H), 1.41 (s, 6H), 1.62 (m, 2H), 2.09 (m, 2H) , 3.02 (s, 3H), 3.16 (m, 1H), 3.30 (m, 1H), 3.41 (d, J = 6.7 Hz, 2H), 3.64 (m, 1H), 3.74 (m, 1H), 4.12 ( m, 1H), 5.71 (brs, 2H), 6.53 (dd, J = 8.4 Hz, J = 1.7 Hz, 1H), 6.87 (d, J = 1.7 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 8.05 (s, 1H), 8.33 (d, J = 7.50Hz, 1H)

Example 83: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-oxo-butyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.38 (m, 2H), 0.49 (m, 2H), 1.07 (m, 1H), 1.40 (s, 6H), 1.61 (m, 2H), 2.07 (m, 2H) , 2.36 (m, 2H), 2.45 (q, J = 7.4 Hz, 2H), 2.57 (s, 3H), 2.76 (m, 2H), 3.01 (s, 2H), 3.22 (s, 2H), 3.39 ( d, J = 6.7 Hz, 2H), 3.47 (m, 1H), 5.69 (brs, 2H), 6.63 (dd, J = 8.4 Hz, J = 1.9 Hz, 1H), 6.78 (d, J = 1.8 Hz, 1H), 7.47 (d, J = 8.4Hz, 1H), 8.23 (d, J = 7.50Hz, 1H)

Example 84: 3- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3 -c] pyridin-1-yl) -phenylamino] -pyrrolidine-1-carboxylic acid tert-butyl ester

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.40 (d, J = 3.6 Hz, 2H), 0.53 (d, J = 6.3 Hz, 2H), 1.05 (m, 1H), 1.42 (s, 6H), 1.42 (s, 6H), 1.49 (s, 9H), 1.98 (br.s, 1H), 2.26 (br.s, 1H), 2.58 (s, 3H), 3.04 (s, 2H), 3.28 (br.s , 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.52 (br.s, 2H), 3.75 (br.s, 1H), 4.12 (m, 1H), 5.67 (br.s, 2H), 6.63 (s, 1H), 6.82 (s, 1H), 7.48 (d, J = 8.1Hz, 1H), 8.30 (d, J = 6.0Hz, 1H)

Example 85: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-isopropylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.05 (m, 1H), 1.20 (d, J = 2.4 Hz, 3H), 1.23 (d, J = 2.4 Hz , 3H), 1.42 (s, 6H), 2.03 (m, 1H), 2.36 (m, 1H), 2.57 (s, 3H), 3.03 (s, 2H), 3.25 (dd, J = 4.2 and 10.2 Hz, 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.48 (m, 2H), 3.59 (m, 1H), 3.72 (dd, J = 6.0 and 10.5 Hz, 1H), 4.17 (m, 2H), 5.83 (brs, 2H), 6.61 (dd, J = 2.1 and 8.4Hz, 1H), 6.80 (d, J = 1.8Hz, 1H), 7.48 (d, J = 8.4Hz, 1H), 8.31 (d, J = 6.6 Hz, 1 H).

Example 86: 2- (1-Chloromethanesulfonyl-pyrrolidin-3-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.06 (m, 1H), 1.42 (s, 6H), 2.14 (m, 1H), 2.39 (m, 1H) , 2.57 (s, 3H), 3.04 (s, 2H), 3.41 (d, J = 6.9 Hz, 2H), 3.48 (dd, J = 4.2 and 10.2 Hz, 1H), 3.71 (m, 2H), 3.92 ( dd, J = 5.4 and 10.2Hz, 1H), 4.25 (m, 1H), 4.58 (s, 2H), 5.80 (brs, 2H), 6.62 (dd, J = 1.8 and 8.4Hz, 1H), 6.84 (d , J = 2.1 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 8.42 (d, J = 6.6 Hz, 1H).

Example 87: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-ethanesulfonyl-piperidin-4-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.05 (m, 1H), 1.40 (m, 9H), 1.75 (m, 2H), 2.12 (m, 2H) , 2.57 (s, 3H), 2.98 (m, 4H), 3.19 (m, 2H), 3.41 (d, J = 6.6 Hz, 2H), 3.65 (m, 3H), 5.74 (brs, 2H), 6.59 ( dd, J = 1.8 and 8.4Hz, 1H), 6.85 (d, J = 1.8Hz, 1H), 7.48 (d, J = 8.4Hz, 1H), 8.34 (d, J = 7.5Hz, 1H).

Example 88: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (propane-1-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.05 (m, 4H), 1.41 (s, 6H), 1.72 (m, 2H), 1.87 (m, 2H) , 2.12 (m, 2H), 2.58 (s, 3H), 2.91 (m, 2H), 3.02 (s, 2H), 3.17 (m, 2H), 3.41 (d, J = 6.6 Hz, 2H), 3.64 ( m, 3H), 5.73 (brs, 2H), 6.55 (dd, J = 1.8 and 8.4Hz, 1H), 6.85 (d, J = 2.1Hz, 1H), 7.48 (d, J = 8.7Hz, 1H), 8.33 (d, J = 7.5 Hz, 1 H).

Example 89 Acetic acid 2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -ethyl ester

¹ H NMR (CDCl ₃ , 300 MHz) 0.41 (m, 2H), 0.51 (m, 2H), 0.93 (m, 1H), 1.40 (s, 6H), 1.69 (m, 2H), 2.01 (m, 2H) , 2.07 (s, 3H), 2.33 (m, 2H), 2.57 (s, 3H), 2.68 (t, J = 6.0Hz, 2H), 2.83 (m, 2H), 3.02 (s, 2H), 3.39 ( d, J = 6.7 Hz, 2H), 3.47 (m, 1H), 4.22 (t, J = 6.0 Hz, 2H), 5.62 (brs, 2H), 6.59 (dd, J = 8.3 Hz, J = 1.9 Hz, 1H), 6.79 (d, J = 8.3 Hz, 1H), 7.47 (d, J = 1.8 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H)

Example 90: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-hydroxy-ethyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.39 (m, 2H), 0.55 (m, 2H), 1.05 (m, 1H), 1.40 (s, 6H), 2.05 (m, 2H), 2.38 (m, 2H) , 2.57 (m, 5H), 2.84 (m, 2H), 3.00 (s, 2H), 3.99 (d, J = 6.8Hz, 2H), 3.48 (m, 1H), 3.62 (m, 2H), 5.66 ( brs, 2H), 6.58 (dd, J = 8.4 Hz, J = 2.0 Hz, 1H), 6.81 (d, J = 2.0 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 7.3 Hz, 1H)

Example 91: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-dimethylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.39 (q, J = 4.8,9.0 Hz, 2H), 0.49-0.55 (m, 2H), 1.04-1.07 (m, 1H), 1.41 (s, 6H), 1.70 (br.s, 3H), 2.01-2.07 (m, 1H), 2.28-2.37 (m, 1H), 2.56 (s, 3H), 2.83 (s, 6H), 3.02 (s, 2H), 3.27 ( dd, J = 3.9, 9.9 Hz, 1H), 3.40 (d, J = 6.6 Hz, 2H), 3.50 (t, J = 6.6 Hz, 2H), 3.71 (dd, J = 5.7, 9.9 Hz, 1H), 4.13-4.21 (m, 1H), 5.83 (br.s, 2H), 6.10 (dd, J = 1.8,8.4Hz, 1H), 6.79 (d, J = 1.8Hz, 1H), 7.48 (d, J = 8.7 Hz, 1 H), 8.38 (d, J = 6.9 Hz, 1 H)

Example 92: 2- [1- (butane-1-sulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.37-0.43 (m, 2H), 0.50-0.56 (m, 2H), 1.05 (m, 1H), 1.41-1.50 (m, 9H), 1.67-1.86 (m , 5H), 2.10-2.17 (m, 2H), 2.58 (s, 3H), 2.91-2.96 (m, 2H), 3.02 (s, 2H), 3.13-3.20 (m, 2H), 3.40 (d, J = 16.5 Hz, 2H), 3.62-3.68 (m, 3H), 5.69 (m, 2H), 6.55 (dd, J = 2.1,8.4 Hz, 1H), 6.86 (s, 1H), 7.47 (d, J = 8.4 Hz, 1 H), 8.33 (d, J = 7.5 Hz, 1 H)

Example 93: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (2-Methyl-propane-1-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.38-0.42 (m, 2H), 0.50-0.56 (m, 2H), 1.05 (m, 1H), 1.13 (s, 6H), 1.41 (s, 6H), 1.68-1.79 (m, 2H), 2.10-2.17 (m, 2H), 2.23-2.36 (m, 1H), 2.58 (s, 3H), 2.78 (d, J = 6.3 Hz, 2H), 3.02 (s, 2H), 3.14 (td, J = 3.0, 9.3 Hz, 2H), 3.40 (d, J = 16.5 Hz, 2H), 3.56-3.68 (m, 3H), 5.68 (m, 2H), 6.55 (dd, J) = 2.1,8.4Hz, 1H), 6.85 (d, J = 2.1Hz, 1H), 7.47 (d, J = 8.4Hz, 1H), 8.33 (d, J = 7.5Hz, 1H)

Example 94: {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4, 3-c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -acetic acid methyl ester

¹ H NMR (CDCl3, 300 MHz) 0.42 (m, 2H), 0.56 (m, 2H), 1.05 (m, 1H), 1.40 (s, 6H), 1.72 (m, 2H), 2.07 (m, 2H) , 2.48 (m, 2H), 2.57 (s, 3H), 2.88 (m, 2H), 3.01 (s, 2H), 3.27 (s, 2H), 3.39 (d, J = 6.7 Hz, 2H), 3.48 ( m, 1H), 3.73 (s , 3H), 5.59 (brs, 2H), 6.54 (dd, J = 2.0Hz, J = 8.4Hz1H), 6.78 (d, J = 1.8Hz, 1H), 7.44 (d, J = 8.5 Hz, 1H), 8.23 (d, J = 7.6 Hz, 1H).

Example 95: 2- [1- (1-Carbamoyl-ethyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.39 (m, 2H), 0.56 (m, 2H), 0.88 (m, 1H), 1.25 (d, J = 6.7 Hz, 3H), 1.40 (s, 6H), 1.65 (m, 2H), 2.08 (m, 2H), 2.39 (t, J = 10.2 Hz, 1H), 2.49 (t, J = 10.1 Hz, 1H), 2.57 (s, 3H), 2.79 (m, 2H) , 3.01 (s, 2H), 3.13 (q, J = 7.0Hz, 1H), 3.39 (d, J = 6.6Hz, 3H), 3.42 (m, 1H), 5.51 (s, 1H), 5.81 (brs, 2H), 6.80 (s, 1H), 7.71 (s, 1H), 7.45 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 7.4 Hz, 1H).

Example 96: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-isopropylsulfamoyl-piperidin-4-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.05 (m, 1H), 1.22 (s, 3H), 1.24 (s, 3H), 1.41 (s, 3H) , 1.43 (s, 3H), 1.65 (m, 2H), 2.13 (m, 2H), 2.58 (s, 3H), 3.02 (s, 2H), 3.05 (m, 2H), 3.42 (d, J = 6.6 Hz, 2H), 3.60 (m, 3H), 4.02 (d, J = 8.1 Hz, 1H), 4.47 (t, J = 7.8 Hz, 1H), 5.76 (brs, 2H), 6.56 (dd, J = 1.8 and 8.4 Hz, 1 H), 6.83 (d, J = 1.8 Hz, 1 H), 7.48 (d, J = 8.7 Hz, 1 H), 8.28 (d, J = 7.5 Hz, 1 H).

Example 97: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-cyclopropylsulfamoyl-piperidin-4-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 0.69 (m, 4H), 1.05 (m, 1H), 1.41 (s, 6H), 1.72 (m, 2H) , 2.12 (m, 2H), 2.58 (m, 4H), 3.02 (s, 2H), 3.14 (m, 2H), 3.41 (d, J = 6.6 Hz, 2H), 3.63 (m, 3H), 4.69 ( s, 1H), 5.74 (brs, 2H), 6.56 (dd, J = 1.8 and 8.4 Hz, 1H), 6.84 (d, J = 1.8 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 8.31 (d, J = 7.5 Hz, 1 H).

Example 98: 2- (1-Chloromethanesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.53 (m, 2H), 1.05 (m, 1H), 1.41 (s, 6H), 1.73 (m, 2H), 2.13 (m, 2H) , 2.58 (s, 3H), 3.02 (s, 2H), 3.34 (m, 2H), 3.41 (d, J = 6.9 Hz, 2H), 3.67 (m, 1H), 3.63 (m, 2H), 4.53 ( s, 2H), 5.71 (brs, 2H), 6.55 (dd, J = 1.8 and 8.4Hz, 1H), 6.87 (d, J = 1.8Hz, 1H), 7.48 (d, J = 8.4Hz, 1H), 8.35 (d, J = 7.5 Hz, 1 H).

Example 99: 2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [ 4,3-c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -propionic acid methyl ester

¹ H NMR (300 MHz, chloroform-d): d 0.37-0.45 (m, 2H), 0.47-0.56 (m, 2H), 1.01-1.09 (m, 1H), 1.31-1.33 (d, J = 6.9 Hz , 3H), 1.40 (s, 6H), 1.66-1.72 (m, 2H), 2.04-2.08 (m, 2H), 2.42-2.55 (m, 2H), 2.58 (s, 3H), 2.85-2.92 (m , 2H), 3.01 (s, 2H), 3.34-3.41 (m, 3H), 3.92 (s, 3H), 5.62 (brs, 2H), 6.63-6.57 (dd, J = 8.4, 2.1 Hz, 1H), 6.78-6.79 (d, J = 1.8Hz, 2H), 7.43-7.46 (d, J = 8.4Hz, 1H), 8.17-8.19 (d, J = 7.5Hz, 1H)

Example 100: 2- (1-Boc-1′-benzylsulfamoyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.40 (m, 2H), 0.54 (m, 2H), 1.06 (m, 1H), 1.41 (s, 6H), 1.49 (s, 9H), 1.62 (m, 2H) , 2.02 (m, 2H), 2.58 (s, 3H), 3.01 (s, 2H), 3.07 (m, 2H), 3.41 (d, J = 6.6 Hz, 2H), 3.59 (m, 3H), 4.88 ( s, 2H), 5.69 (brs, 2H), 6.54 (dd, J = 1.8 and 8.4Hz, 1H), 6.81 (s, 1H), 7.33 (m, 5H), 7.46 (d, J = 8.4Hz, 1H 8.25 (d, J = 7.2 Hz, 1H).

Example 101: 2- (1-benzylsulfamoyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6 , 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.32 (s, 6H), 1.35 (m, 2H), 1.96 (m, 2H), 2.40 (s, 3H), 2.91 (m, 2H), 3.17 (s, 2H), 3.31 (d, J = 6.6 Hz, 2H), 3.41 (m, 2H), 3.57 (m, 1H), 4.10 (d, J = 6.0Hz, 2H),), 6.70 (dd, J = 1.8 and 8.4Hz, 1H), 6.78 (d, J = 1.8Hz, 1H), 7.27 (m, 2H), 7.35 (m , 5H), 7.75 (d, J = 8.4 Hz, 1H), 7.82 (m, 1H), 7.95 (brs, 1H).

Example 102: 2- [1- (2- (cyclopropylamino-acetyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.22 (m, 2H), 0.40 (m, 2H), 0.55 (m, 4H), 1.05 (m, 2H), 1.41 (s, 6H), 1.69 (m, 2H) , 2.12 (m, 2H), 2.58 (s, 3H), 2.93 (m, 2H), 3.02 (s, 2H), 3.08 (m, 2H), 3.40 (d, J = 6.9 Hz, 2H), 3.62 ( m, 3H), 4.42 (t, J = 5.7 Hz, 1H),), 5.85 (brs, 2H), 6.54 (dd, J = 2.1 and 8.4 Hz, 1H), 6.84 (d, J = 1.8 Hz, 1H ), 7.48 (d, J = 8.4 Hz, 1 H), 8.29 (d, J = 7.5 Hz, 1 H).

Example 103: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (1-Methyl-2-oxo-propyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.37 (m, 2H), 0.52 (m, 2H), 1.05 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H), 1.37 (s, 6H), 1.69 (m, 2H), 2.04 (m, 2H), 2.31 (t, J = 8.3 Hz, 1H), 2.49 (t, J = 8.3 Hz, 1H), 2.57 (s, 3H), 2.71 (m, 2H) , 3.02 (s, 2H), 3.17 (q, J = 6.9Hz, 1H), 3.41 (d, J = 6.7Hz, 2H), 3.42 (m, 1H), 5.64 (brs, 2H), 6.55 (dd, J = 8.4 Hz, J = 2.0 Hz, 1 H), 6.79 (d, J = 1.8 Hz, 1 H), 7.47 (d, J = 8.5 Hz, 1 H), 8.18 (d, J = 7.4 Hz, 1 H).

Example 104: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (1-dimethylcarbamoylmethyl-piperidin-4-yl-amino) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.37 (m, 2H), 0.56 (m, 2H), 0.9 (m, 1H), 1.40 (s, 6H), 1.69 (m, 2H), 2.06 (m, 2H) , 2.35 (m, 2H), 2.57 (s, 3H), 2.84 (m, 2H), 2.95 (s, 3H), 3.02 (s, 2H), 3.08 (s, 3H), 3.20 (s, 2H), 3.41 (d, J = 6.7 Hz, 2H), 3.42 (m, 1H), 5.62 (brs, 2H), 6.60 (dd, J = 8.4Hz, J = 2.0Hz, 1H), 6.77 (d, J = 1.9 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 7.3 Hz, 1H).

Example 105: 4- [2-carbamoyl-5- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyra Zolo [4,3-c] pyridin-1-yl) -phenylamino] -piperidine-1-carboxylic acid tert-butyl ester

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.40-0.43 (m, 2H), 0.49-0.55 (m, 2H), 1.03-1.08 (m, 1H), 1.43 (s, 6H), 1.48 (s, 1H ), 2.01 (d, J = 16.5Hz, 2H), 3.05 (s, 2H), 3.09-3.14 (m, 2H), 3.43 (d, J = 16.5Hz, 2H), 3.57 (m, 1H), 3.93 (d, J = 7.5 Hz, 2H), 5.71 (br.s, 2H), 6.56 (dd, J = 2.1, 8.4 Hz, 1H), 6.81 (d, J = 2.1 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1 H), 8.26 (d, J = 7.5 Hz, 1 H)

Example 106: 4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -2- (piperidin-4-yl-amino) -benzamide;

¹ H NMR (300 MHz, DMSO-d6) δ 0.30-0.35 (m, 2H), 0.40-0.48 (m, 2H), 0.98-1.04 (m, 1H), 1.29 (s, 6H), 1.52-1.64 ( m, 2H), 2.13 (d, J = 12.3 Hz, 2H), 3.09 (m, 2H), 3.28 (m, 2H), 3.34 (d, J = 6.6 Hz, 2H), 3.71 (m, 1H), 4.55 (m, 4H), 6.78 (dd, J = 1.8,8.4Hz, 1H), 6.91 (d, J = 1.8Hz, 1H), 7.42 (br.s, 1H), 7.82 (d, J = 8.4Hz , 1H), 8.07 (br.s, 1H), 8.73-8.81 (m, 1H), 8.90-8.96 (m, 1H)

Example 107: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (1-dimethylcarbamoyl-ethyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, chloroform-d): d 0.37-0.42 (m, 2H), 0.50-0.56 (m, 2H), 1.01-1.12 (m, 1H), 1.18-1.21 (d, J = 6.9 Hz , 3H), 1.40 (s, 6H), 1.54-1.71 (m, 2H), 2.02-2.06 (m, 2H), 2.34-2.40 (m, 1H), 2.57 (s, 3H), 2.57-2.63 (m , 1H), 2.76-2.80 (m, 2H), 2.96 (s, 3H), 3.01 (s, 2H), 3.14 (s, 3H), 3.39-3.41 (d, J = 6.6Hz, 2H), 3.54- 3.61 (dd, J = 13.4,6.6 Hz, 2H), 5.57 (brs, 2H), 6.55-6.59 (dd, J = 8.4,1.8 Hz, 1H), 6.76-6.76 (d, J = 1.5 Hz, 1H) , 7.44-7.47 (d, J = 8.4 Hz, 1H), 8.14-8.16 (d, J = 7.2 Hz, 1H)

Example 108: 2- [1- (Cyclopropylmethyl-sulfamoyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamidetetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.19 (m, 2H), 0.40 (m, 2H), 0.53 (m, 4H), 1.04 (m, 2H), 1.42 (s, 6H), 2.05 (m, 1H) , 2.36 (m, 1H), 2.57 (s, 3H), 2.94 (dd, J = 6.0 and 7.2 Hz, 2H), 3.03 (s, 2H), 3.28 (dd, J = 3.9 and 10.2 Hz, 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.51 (m, 2H), 3.72 (dd, J = 6.0 and 10.2 Hz, 1H), 4.19 (m, 1H), 4.45 (t, J = 5.7 Hz, 1H ), 5.84 (brs, 2H), 6.60 (dd, J = 1.8 and 8.4 Hz, 1H), 6.80 (d, J = 1.8 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 8.34 (d , J = 6.6 Hz, 1 H).

Example 109: 2- [1- (4-Cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.19 (m, 2H), 0.40 (m, 2H), 0.53 (m, 4H), 1.04 (m, 2H), 1.42 (s, 6H), 2.05 (m, 1H) , 2.36 (m, 1H), 2.57 (s, 3H), 2.94 (dd, J = 6.0 and 7.2 Hz, 2H), 3.03 (s, 2H), 3.28 (dd, J = 3.9 and 10.2Hz, 1H), 3.41 (d, J = 6.6 Hz, 2H), 3.51 (m, 2H), 3.72 (dd, J = 6.0 and 10.2 Hz, 1H), 4.19 (m, 1H), 4.45 (t, J = 5.7 Hz, 1H ), 5.84 (brs, 2H), 6.60 (dd, J = 1.8 and 8.4 Hz, 1H), 6.80 (d, J = 1.8 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 8.34 (d , J = 6.6 Hz, 1 H).

Example 110: (2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -2-oxo-ethyl) -carbamic acid tert-butyl ester

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.36-0.41 (m, 2H), 0.46-0.54 (m, 2H), 0.98-1.05 (m, 1H), 1.43 (m, 15H), 1.48-1.60 (m , 1H), 2.05 (t, J = 12.6 Hz, 2H), 3.03 (s, 2H), 3.10-3.21 (m, 2H), 3.41 (d, J = 6.9 Hz, 2H), 3.53-3.67 (m, 2H), 3.93 (d, J = 4.2Hz, 2H), 4.20 (d, J = 13.8Hz, 1H), 5.50 (s, 1H), 6.04 (m, 2H), 6.51 (d, J = 1.8,8.4 Hz, 1H), 6.88 (d, J = 2.1 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 8.34 (d, J = 7.5 Hz, 1H)

Example 111: 2- [1- (2-cyclopropylamino-acetyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3 -Trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.35-0.45 (m, 6H), 0.49-0.55 (m, 2H), 0.80-0.92 (m, 2H), 0.98-1.10 (m, 2H), 1.43 (s , 6H), 1,54-1.65 (m, 4H), 2.05-2.10 (m, 1H), 2.18-2.24 (m, 1H), 3.05 (s, 2H), 3.14-3.31 (m, 2H), 3.43 (d, J = 6.9 Hz, 2H), 3.52 (s, 2H), 3,64-3.77 (m, 2H), 4,26 (d, J = 14.4 Hz, 1H), 5.77 (m, 2H), 6.56 (dd, J = 1.8,8.4Hz, 1H), 6.84 (d, J = 2.1Hz, 1H), 7.52 (d, J = 8.4Hz, 1H), 8.33 (d, J = 7.5Hz, 1H)

Example 112: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 0.44-0.49 (m, 2H), 0.57-0.63 (m, 2H), 1.09 (m, 1H), 1.45 (s, 6H), 2.14-2.19 (m, 2H ), 2.39 (s, 3H), 2.53 (t, J = 4.5,9.6Hz, 4H), 2.65 (s, 3H), 3.09 (s, 2H), 3.90 (td, J = 2.1,12.6Hz, 2H) , 3.62 (t, J = 4.5,9.6Hz, 4H), 3.47 (d, J = 6.6Hz, 2H), 3.66-3.72 (m, 3H), 5.79 (br.s, 2H), 6.62 (dd, J = 1.8,8.4Hz, 1H), 6.90 (d, J = 2.1Hz, 1H), 7.54 (d, J = 8.4Hz, 1H), 8.36 (d, J = 7.5Hz, 1H)

Example 113: 2- (1- (4-Amido-benzenesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo -4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.00 (m, 1H), 1.27 (s, 6H), 1.43 (m, 2H), 2.02 (m, 2H), 2.37 (s, 3H), 2.59 (m, 2H), 3.10 (s, 2H), 3.29 (d, J = 8.4 Hz, 2H), 3.55 (m, 3H), 6.67 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 7.24 (brs, 1H), 7.66 (s, 1H), 7.71 (d, J = 8.4Hz, 1H), 7.83 (d, J = 8.4Hz, 2H), 7.91 (brs, 1H), 8.10 (d, J = 8.1 Hz, 2H), 8.22 (s, 1H), 8.41 (d, J = 7.8 Hz, 1H).

Example 114: 2- [1- (4-Aminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.00 (m, 1H), 1.27 (s, 6H), 1.43 (m, 2H), 2.02 (m, 2H), 2.37 (s, 3H), 2.59 (m, 2H), 3.10 (s, 2H), 3.29 (d, J = 8.4 Hz, 2H), 3.55 (m, 3H), 6.67 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 7.24 (brs, 1H), 7.66 (s, 1H), 7.71 (d, J = 8.4Hz, 1H), 7.83 (d, J = 8.4Hz, 2H), 7.91 (brs, 1H), 8.10 (d, J = 8.1 Hz, 2H), 8.22 (s, 1H), 8.41 (d, J = 7.8 Hz, 1H).

Example 115: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (1-Methyl-2-morpholin-4-yl-2-oxo-ethyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, chloroform-d): d 0.37-0.42 (m, 2H), 0.50-0.56 (m, 2H), 1.00-1.09 (m, 1H), 1.19-1.21 (d, J = 6.6 Hz , 3H), 1.40 (s, 6H), 1.49-1.63 (m, 2H), 2.03-2.07 (m, 2H), 2.34-2.41 (m, 1H), 2.54-2.61 (m, 1H), 2.57 (s , 3H), 2.73-2.77 (m, 2H), 3.01 (s, 2H), 3.39-3.41 (d, J = 6.6 Hz, 2H), 3.49-3.82 (m, 10H), 5.70 (brs, 2H), 6.54-6.57 (dd, J = 8.4,1.8 Hz, 1H), 6.77-6.78 (d, J = 1.8 Hz, 1H), 7.44-7.47 (d, J = 8.4 Hz, 1H), 8.15-8.17 (d, J = 7.5 Hz, 1H)

Example 116 2- [1- (3-Cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, chloroform-d): d 0.37-0.42 (m, 2H), 0.47-0.55 (m, 2H), 1.02-1.11 (m, 1H), 1.39 (s, 6H), 1.68-1.80 (m, 2H), 2.10-2.15 (m, 2H), 2.54 (s, 3H), 2.78-2.85 (m, 2H), 2.99 (s, 2H), 3.38-3.40 (d, J = 6.6 Hz, 2H ), 3.49-3.64 (m, 3H), 5.64 (brs, 2H), 6.48-6.52 (dd, J = 8.3,1.8Hz, 1H), 6.80 (d, J = 1.8Hz, 1H), 7.43-7.45 ( d, J = 8.4 Hz, 1H), 7.69-7.74 (t, J = 7.8 Hz, 1H), 7.89-7.92 (m, 1H), 8.00-8.02 (m, 1H), 8.07 (m, 1H), 8.22 -8.25 (d, J = 7.8 Hz, 1H)

Example 117: 2- (1- (3-Amido-benzenesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo -4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d ₆ ): d 0.29-0.34 (m, 2H), 0.42-0.48 (m, 2H), 0.99-1.05 (m, 1H), 1.26 (s, 6H), 1.38- 1.48 (m, 2H), 2.01-2.05 (m, 2H), 2.36 (s, 3H), 2.54-2.60 (m, 2H), 3.10 (s, 2H), 3.28-3.31 (m, 2H), 3.44- 3.58 (m, 3H), 6.66-6.71 (m, 2H), 7.23 (brs, 1H), 7.64 (s, 1H), 7.70-7.78 (m, 2H), 7.88-7.91 (m, 2H), 8.20- 8.23 (m, 2H), 8.29 (s, 1H), 8.40-8.42 (d, J = 7.8 Hz, 1H)

Example 118: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (4-methanesulfonylamino-cyclohexylamino) -benzamide

¹ H NMR (DMSO- d6 , 300MHz) 0.32 (m, 2H), 0.45 (m, 2H), 1.03 (m, 1H), 1.22 (m, 2H), 1.32 (s, 6H), 1.393 (m, 2H ), 1.90 (m, 2H), 2.05 (m, 2H), 2.40 (s, 3H), 2.91 (s, 3H), 3.17 (m, 3H), 6.67 (dd, J = 8.4 Hz, J = 1.6 Hz , 1H), 6.76 (d, J = 1.6 Hz, 1H), 7.05 (d, J = 7 Hz, 1H), 7.22 (brs, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.90 (brs, 1H), 8.39 (d, J = 7.5 Hz, 1H) ..

Example 119: 2- (4-acetylamino-cyclohexylamino) -4- (5-cyclopropyl methyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyra Zolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO- d6 , 300MHz) 0.29 (m, 2H), 0.42 (m, 2H), 1.02 (m, 1H), 1.24 (m, 4H), 1.31 (s, 6H), 1.78 (s, 3H ), 1.83 (m, 2H), 2.05 (m, 2H), 2.40 (s, 3H), 3.15 (m, 4H), 3.50 (m, 1H), 6.64 (dd, J = 8.4 Hz, J = 1.7 Hz , 1H), 6.77 (d, J = 1.7 Hz, 1H), 7.22 (brs, 1H), 7.73 (d, J = 8.5 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.90 (brs , 1H), 8.40 (d, J = 7.6 Hz, 1H).

Example 120: 2- [1- (3-Aminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d ₆ ): d 0.28-0.33 (m, 2H), 0.41-0.47 (m, 2H), 0.78-0.90 (m, 2H), 0.92-1.08 (m, 2H), 1.27 (s, 6H), 1.35-1.47 (m, 3H), 2.00-2.03 (m, 2H), 2.36 (s, 3H), 2.56-0.60 (m, 2H), 3.10 (s, 2H), 3.50- 3.53 (m, 4H), 3.81 (s, 1H), 6.65-6.67 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 7.23 (brs, 1H), 7.56-7.59 (m, 2H) , 7.64-7.67 (m, 1H), 7.70-7.74 (m, 2H), 7.90 (brs, 1H), 8.40-8.42 (d, J = 7.8Hz, 1H)

Example 121: 2- [1- (2-Cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d ₆ ): d 0.29-0.34 (m, 2H), 0.42-0.48 (m, 2H), 0.97-1.07 (m, 1H), 1.29 (s, 6H), 1.37- 1.49 (m, 2H), 2.04-2.08 (m, 2H), 2.38 (s, 3H), 2.81-2.89 (m, 2H), 3.13 (s, 2H), 3.29-3.31 (m, 2H), 3.56- 3.67 (m, 3H), 6.67-6.70 (m, 1H), 6.73 (m, 1H), 7.25 (brs, 1H), 7.72-7.74 (d, J = 8.4 Hz, 1H), 7.87-7.95 (m, 2H), 7.98-8.00 (m, 1H), 8.03-8.06 (m, 1H), 8.17-8.20 (dd, J = 7.4, 1.5 Hz, 1H), 8.44-8.47 (d, J = 7.8 Hz, 1H)

Example 122: 2- [1- (3-Cyano-4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6 -Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.01 (m, 1H), 1.28 (s, 6H), 1.44 (m, 2H), 2.03 (m, 2H), 2.37 (s, 3H), 2.62 (m, 2H), 3.12 (s, 2H), 3.30 (d, J = 7.2 Hz, 2H), 3.56 (m, 3H), 6.67 (d, J = 7.5 Hz, 1H), 6.70 (s, 1H), 7.25 (brs, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.83 (t, J = 9.0 Hz, 1H), 7.74 (brs, 1H), 8.16 (m, 1 H), 8.41 (m, 2 H).

Example 123: 2- [1- (3-Aminomethyl-4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6 -Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.00 (m, 1H), 1.27 (s, 6H), 1.44 (m, 2H), 2.02 (m, 2H), 2.37 (s, 3H), 2.58 (m, 2H), 3.11 (s, 2H), 3.29 (m, 2H), 3.52 (m, 5H), 3.84 (s, 2H), 6.66 (dd, J = 1.5 and 8.4 Hz, 1H), 6.72 (s, 1H), 7.24 (brs, 1H), 7.42 (t, J = 9.6 Hz, 1H), 7.67 (m, 1H), 7.72 (d, J = 8.4 Hz , 1H), 7.88 (m, 1H), 7.95 (dd, J = 1.8 and 6.9 Hz, 1H), 8.42 (d, J = 7.5 Hz, 1H).

Example 124 2- [1- (4-Bromomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.39 (m, 2H), 0.52 (m, 2H), 1.04 (m, 1H), 1.39 (s, 6H), 1.73 (m, 2H), 2.11 (m, 2H) , 2.54 (s, 3H), 2.70 (m, 2H), 2.98 (s, 2H), 3.39 (d, J = 6.9 Hz, 2H), 3.65 (m, 3H), 4.52 (s, 2H), 5.64 ( brs, 2H), 6.50 (dd, J = 1.8 and 8.4Hz, 1H), 6.78 (d, J = 1.8Hz, 1H), 7.44 (d, J = 8.4Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 7.5 Hz, 1H).

Example 125: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (4-Dimethylaminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.39 (m, 2H), 0.53 (m, 2H), 1.04 (m, 1H), 1.39 (s, 6H), 1.46 (m, 2H), 2.08 (m, 2H) , 2.28 (s, 6H), 2.54 (s, 3H), 2.71 (m, 2H), 2.98 (s, 2H), 3.41 (m, 3H), 3.51 (s, 2H), 3.58 (m, 2H), 5.70 (brs, 2H), 6.50 (dd, J = 1.8 and 8.4Hz, 1H), 6.77 (d, J = 1.8Hz, 1H), 7.43 (d, J = 8.7Hz, 1H), 7.50 (d, J = 8.1 Hz, 2H), 7.73 (d, J = 8.1 Hz, 2H), 8.17 (d, J = 7.8 Hz, 1H).

Example 126: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (4-piperidin-1-yl-methyl-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.39 (m, 2H), 0.53 (m, 2H), 1.04 (m, 1H), 1.38 (s, 6H), 1.46 (m, 2H), 1.59 (m, 2H) , 1.71 (m, 4H), 2.10 (m, 2H), 2.40 (m, 4H), 2.54 (s, 3H), 2.67 (m, 2H), 2.98 (s, 2H), 3.40 (m, 3H), 3.53 (s, 2H), 3.61 (m, 2H), 5.74 (brs, 2H), 6.48 (dd, J = 1.8 and 8.4 Hz, 1H), 6.77 (d, J = 1.8 Hz, 1H), 7.44 (d , J = 8.4 Hz, 1H), 7.51 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 8.16 (d, J = 7.5 Hz, 1H).

Example 127: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [4- (4-fluoro-benzenesulfonylamino) -cyclohexylamino] -benzamide

¹ H NMR (DMSO- d6 , 300MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.08 (m, 1H), 1.28 (s, 6H), 1.35 (m, 4H), 1.62 (m, 2H ), 1.97 (m, 2H), 2.39 (s, 3H), 2.99 (s, 2H), 3.13 (s, 2H), 6.63 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 6.70 (d , J = 1.5 Hz, 1H), 7.20 (brs, 1H), 7.45 (m, 2H), 7.68 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 6.2 Hz, 1H), 7.91 (m , 3H), 8.33 (d, J = 7.6 Hz, 1H).

Example 128: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (4-isopropyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.31 (d, J = 3.6 Hz, 2H), 0.43 (d, J = 7.2 Hz, 2H), 0.85-0.97 (m, 1H), 1.32 (s, 6H ), 1.39-1.46 (m, 2H), 2.01 (d, J = 11.4 Hz, 2H), 2.40 (s, 3H), 2.63-2.69 (m, 1H), 3.06-3.18 (m, 9H), 3.49 ( d, J = 9.0 Hz, 2H), 3.65 (m, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.79 (s, 1H), 7.28 (br.s, 1H), 7.75 (d, J = 8.4 Hz, 1 H), 7.94 (br.s, 1 H), 8.53 (d, J = 7.5 Hz, 1 H)

Example 129: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (4-methyl- [1,4] diazepan-1-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.31 (d, J = 3.6 Hz, 2H), 0.44 (d, J = 6.9 Hz, 2H), 0.99 (m, 1H), 1.31 (s, 6H), 1.38-1.44 (m, 2H), 1.80 (m, 2H), 2.01 (d, J = 11.4 Hz, 2H), 2.25 (s, 3H), 2.40 (s, 3H), 3.00 (t, J = 10.8 Hz , 2H), 3.18 (s, 2H), 3.63 (m, 1H), 6.70 (d, J = 8.1Hz, 1H), 7.28 (br.s, 1H), 7.75 (d, J = 8.4Hz, 1H) , 7.95 (s, 1H), 8.54 (d, J = 7.5Hz, 1H)

Example 130: 4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [ 4,3-c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl}-[1,4] diazepane-1-carboxylic acid tert-butyl ester

¹ H NMR (300 MHz, DMSO-d6) δ 0.31-0.32 (m, 2H), 0.42-0.45 (m, 2H), 1.23 (s, 3H), 1.32 (s, 6H), 1.39 (m, 9H) , 1.71-1.73 (m, 2H), 1.99-2.03 (m, 2H), 2.40 (s, 3H), 2.99 (t, J = 10.2Hz, 1H), 3.17 (m, 1H), 3.50 (m, 1H ), 3.60 (m, 2H), 6.70 (d, J = 8.7Hz, 1H), 6.80 (s, 1H), 7.28 (br.s, 1H), 7.75 (d, J = 8.4Hz, 1H), 7.91 (br.s, 1H), 8.54 (d, J = 7.5Hz, 1H)

Example 131: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (morpholin-4-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.29-0.34 (m, 2H), 0.41-0.47 (m, 2H), 0.98-1.06 (m, 1H), 1.31 (s, 6H), 1.42-1.50 ( m, 2H), 1.99-2.03 (m, 2H), 2.40 (s, 3H), 3.10-3.13 (m, 6H), 3.18 (s, 2H), 3.50 (t, J = 6.9 Hz, 4H), 3.62 (t, J = 4.5Hz, 6H), 6.70 (d, J = 8.4Hz, 1H), 6.80 (d, J = 1.2Hz, 1H), 7.29 (br.s, 1H), 7.75 (d, J = 8.4 Hz, 1 H), 7.95 (br.s, 1 H), 8.55 (d, J = 7.8 Hz, 1 H)

Example 132 N- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [ 4,3-c] pyridin-1-yl) -phenylamino] -cyclohexyl} -isonicotinamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.362 (m, 2H), 0.55 (m, 2H), 1.04 (m, 1H), 1.40 (s, 6H), 1.48 (m, 4H), 2.22 (m, 4H) , 2.57 (s, 3H), 3.02 (s, 2H), 3.41 (m, 3H), 4.04 (m, 1H), 5.72 (brs, 2H), 6.16 (d, J = 7.8Hz, 1H), 6.51 ( dd, J = 8.4Hz, J = 1.8Hz, 1H), 6.81 (d, J = 1.8Hz, 1H), 7.45 (d, J = 8.4Hz, 1H), 7.61 (d, J = 6.1Hz, 2H) , 8.09 (d, J = 7.4 Hz, 1H), 8.75 (d, J = 5.9 Hz, 2H).

Example 133: 2- [1- (4-Fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d6): d 1.18 (s, 6H), 1.37-1.49 (m, 2H), 1.99-2.03 (m, 2H), 2.37 (s, 3H), 2.56-2.62 (m , 2H), 2.98 (s, 2H), 3.47-3.51 (m, 3H), 6.62-6.67 (d, J = 8.3 Hz, 1H), 6.73-6.74 (d, J = 1.5 Hz, 1H), 7.25 ( brs, 1H), 7.30 (s, 1H), 7.47-7.54 (t, J = 8.7 Hz, 2H), 7.70-7.73 (d, J = 8.4 Hz, 1H), 7.81-7.85 (m, 2H), 7.91 (brs, 1H), 8.41-8.43 (d, J = 7.8 Hz, 1H)

Example 134 N- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [ 4,3-c] pyridin-1-yl) -phenylamino] -cyclohexyl} -nicotinamide

¹ H NMR (CDCl ₃ , 300 MHz) 0.32 (m, 2H), 0.52 (m, 2H), 1.05 (m, 1H), 1.43 (s, 6H), 1.51 (m, 4H), 2.26 (m, 4H) , 2.59 (s, 3H), 3.05 (s, 2H), 3.40 (m, 3H), 4.10 (m, 1H), 5.69 (brs, 2H), 6.04 (d, J = 7.8Hz, 1H), 6.58 ( dd, J = 8.4Hz, J = 1.8Hz, 1H), 6.84 (d, J = 1.7Hz, 1H), 7.40 (m, 1H), 7.49 (d, J = 8.5Hz, 1H), 8.12 (m, 2H), 8.70 (m, 1H), 8.97 (s, 1H)

Example 135: 4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [ 4,3-c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -benzoic acid

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.45 (m, 2H), 1.00 (m, 1H), 1.27 (s, 6H), 1.43 (m, 2H), 2.03 (m, 2H), 2.37 (s, 3H), 2.59 (m, 2H), 3.10 (s, 2H), 3.29 (d, J = 6.9 Hz, 2H), 3.53 (m, 3H), 6.67 (dd, J = 1.5 and 8.4 Hz, 1H), 6.71 (s, 1H), 7.14 (brs, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.91 (brs, 1H) ), 8.10 (d, J = 8.4 Hz, 2H), 8.22 (s, 1H), 8.41 (d, J = 8.1 Hz, 1H).

Example 136: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (4-ethoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.32 (m, 2H), 0.44 (m, 2H), 1.01 (m, 1H), 1.27 (s, 6H), 1.35 (t, J = 6.9 Hz, 3H) , 1.42 (m, 2H), 2.02 (m, 2H), 2.37 (s, 3H), 2.54 (m, 2H), 3.11 (s, 2H), 3.32 (m, 2H), 3.50 (m, 3H), 4.12 (m, 2H), 6.67 (d, J = 8.7 Hz, 1H), 6.72 (s, 1H), 7.14 (d, J = 9.0 Hz, 2H), 7.23 (brs, 1H), 7.66 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.4 Hz, 1H), 7.91 (brs, 1H), 8.41 (d, J = 7.8 Hz, 1H).

Example 137: 2- [1- (3-Cyano-4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6 -Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.02 (m, 1H), 1.28 (s, 6H), 1.43 (m, 2H), 2.03 (m, 2H), 2.38 (s, 3H), 2.56 (m, 2H), 3.12 (s, 2H), 3.30 (d, J = 6.6 Hz, 2H), 3.53 (m, 3H), 4.02 (s, 3H), 6.67 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 7.14 (brs, 1H), 7.50 (d, J = 9.3 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.92 (brs, 1 H), 8.03 (dd, J = 2.4 and 9.0 Hz, 1 H), 8.12 (d, J = 2.4 Hz, 1 H), 8.42 (d, J = 7.8 Hz, 1 H).

Example 138: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (3-amido, 4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.01 (m, 1H), 1.27 (s, 6H), 1.43 (m, 2H), 2.04 (m, 2H), 2.37 (s, 3H), 2.54 (m, 2H), 3.11 (s, 2H), 3.29 (d, J = 6.9 Hz, 2H), 3.45-3.55 (m, 3H), 3.98 (s, 3H ), 6.67 (d, J = 10.2 Hz, 1H), 6.72 (s, 1H), 7.24 (brs, 1H), 7.38 (d, J = 9.0 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H ), 7.77 (d, J = 6.9 Hz, 2H), 7.84 (dd, J = 2.4 and 8.7 Hz, 1H), 7.91 (brs, 1H), 8.10 (d, J = 2.4 Hz, 1H), 8.41 (d , J = 7.8 Hz, 1H).

Example 139: 4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- [1- (3-acetic acid, 4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.43 (m, 2H), 1.01 (m, 1H), 1.28 (s, 6H), 1.43 (m, 2H), 2.03 (m, 2H), 2.37 (s, 3H), 2.54 (m, 2H), 3.11 (s, 2H), 3.29 (d, J = 6.6 Hz, 2H), 3.49 (m, 3H), 3.81 (s, 3H), 6.66 (d, J = 8.1 Hz, H), 6.67 (s, 1H), 6.87 (s, 1H), 7.17 (d, J = 8.7 Hz, 1H), 7.26 (brs, 1H), 7.61 (m, 2H ), 7.72 (d, J = 8.4 Hz, 1H), 7.91 (brs, 1H), 8.41 (d, J = 7.2 Hz, 1H

Example 140: 4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [ 4,3-c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -cyclohexa-1-enecarboxylic acid

¹ H NMR (DMSO-d6, 300 MHz) 0.31 (m, 2H), 0.44 (m, 2H), 1.01 (m, 1H), 1.31 (s, 6H), 1.41 (m, 2H), 1.62 (m, 1H), 1.88-2.06 (m, 3H), 2.30 (m, 2H), 2.39 (s, 3H), 2.39-2.44 (m, 3H), 2.95 (m, 2H), 3.18 (s, 2H), 3.31 (d, J = 6.6 Hz, 2H), 3.39-3.45 (m, 3H), 3.62 (m, 1H), 6.64 (s, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.79 (s, 1H), 7.28 (brs, 1H), 7.75 (d, J = 8.4Hz, 1H), 7.94 (brs, 1H), 8.52 (d, J = 7.8Hz, 1H)

Example 141: 4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -2- [1- (1-methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 2.75 (m, 2H), 3.18 (s, 2H), 3.30-3.41 (m, 3H), 3.5 (m, 2H), 3.71 (s, 3H), 6.73 ( dd, J = 1.8 and 8.4 Hz, 1H), 6.87 (d, J = 1.5 Hz, 1H), 7.35 (brs, 1H), 7.77 (d , J = 8.4 Hz, 1H), 7.83 (m, 2H), 8.00 (brs, 1H), 8.44 (d, J = 7.8 Hz, 1H).

Example 142 4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -2- {1- [4- (4-methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide

¹ H NMR (CDCl3, 300 MHz) 0.41 (m, 2H), 0.52 (m, 2H), 1.06 (m, 1H), 1.41 (s, 6H), 1.69 (m, 2H), 2.10 (m, 2H) , 2.36 (s, 3H), 2.56 (m, 6H), 3.01 (s, 2H), 3.36 (m, 4H), 3.43 (d, 2H), 3.67 (m, 3H), 5.71 (brs, 2H), 6.50 (dd, J = 2.1 and 8.4 Hz, 1H), 6.73 (d, J = 1.8 Hz, 1H), 6.92 (d, J = 9.0 Hz, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 9.0 Hz, 2H), 8.16 (d, J = 7.5 Hz, 1H).

Example 143: 4- (3-dimethylaminomethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- (4-hydroxycyclohexylamino) -benzamide

¹ H NMR (300 MHz, DMSO-d ₆ ): d 1.02 (t, J = 6.9 Hz, 6H), 1.22 (s, 6H), 1.22-1.37 (m, 4H), 1.81-1.84 (m, 2H) , 1.98-2.02 (m, 2H), 2.54 (q, J = 7.2 Hz, 4H), 3.06 (s, 2H), 3.44-3.51 (m, 2H), 3.94 (s, 2H), 4.12-4.15 (m , 1H), 6.65 (d, J = 8.7Hz, 1H), 6.81 (s, 1H), 7.22 (brs, 1H), 7.31 (s, 1H), 7.73 (d, J = 8.7Hz, 1H), 7.90 (brs, 1H), 8.37 (d, J = 7.5 Hz, 1H)

Example 144 2- (1-benzenesulfonyl-piperidin-4-yl-amino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro- Pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO- d6 , 300MHz) 1.17 (s, 6H), 1.43 (m, 2H), 2.02 (m, 2H), 2.35 (s, 3H), 2.57 (m, 2H), 2.96 (s, 2H ), 3.54 (m, 2H), 6.62 (dd, J = 8.5 Hz, J = 1.8 Hz, 1H), 6.72 (d, J = 1.8 Hz, 1H), 7.24 (brs, 1H), 7.29 (s, 1H) ), 7.76 (m, 6H), 7.91 (brs, 1H), 8.39 (d, J = 7.8 Hz, 1H).

Example 145 2- [4- (4-Fluoro-benzenesulfonylamino) -cyclohexylamino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 1.35 (m, 10H), 1.92 (m, 2H), 2.05 (m, 2H), 2.58 (s, 3H), 2.95 (s, 2H), 3.18 (m, 1H) , 3.33 (m, 1H), 4.86 (d, J = 7.6 Hz, 1H), 5.35 (s, 1H), 5.65 (brs, 2H), 6.49 (dd, J = 8.5 Hz, J = 1.9 Hz, 1H) , 6.78 (d, J = 1.6Hz, 1H), 7.20 (m, 2H), 7.42 (d, J = 8.4Hz, 1H), 7.89 (m, 2H), 8.07 (d, J = 7.6Hz, 1H) .

Example 146 N- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -phenylamino] -cyclohexyl} -isonicotinamide

¹ H NMR (CDCl ₃ , 300 MHz) 1.36 (s, 6H), 1.46 (m, 4H), 2.23 (m, 4H), 2.57 (s, 3H), 2.97 (s, 2H), 3.42 (s, 1H) , 4.08 (s, 1H), 5.15 (s, 1H), 5.67 (brs, 2H), 6.04 (d, J = 8.3Hz, 1H), 6.52 (dd, J = 8.4Hz, J = 2.0Hz, 1H) , 6.83 (d, J = 1.8Hz, 1H), 7.45 (d, J = 8.4Hz, 1H), 7.58 (m, 2H), 8.14 (d, J = 7.5Hz, 1H), 8.74 (m, 2H)

Example 147: 2- [1- (imidazol-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6 , 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 1.02 (s, 6H), 1.18-1.28 (m, 2H), 1.81-1.86 (m, 2H), 2.20 (s, 3H), 2.68-2.87 (m, 5H), 3.37-3.51 (m, 4H), 6.48 (dd, J = 1.5, 8.4 Hz, 1H), 6.60 (s, 1H), 7.00 (s, 1H), 7.08 (br.s, 1H), 7.13 (s, 1H), 7.47 (m, 1H), 7.55 (d, J = 8.4Hz, 1H), 7.75 (br.s, 1H), 8.01 (s, 1H), 8.26 (d, J = 7.5Hz, 1H)

Example 148 2- [1- (4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4 , 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 1.04 (s, 6H), 1.13-1.30 (m, 2H), 1.81-1.84 (m, 2H), 2.02 (s, 3H), 2.16-2.19 (m, 4H), 2.22 (s, 3H), 2.87 (s, 2H), 2.91 (m, 2H), 2.95-2.98 (m, 4H), 3.24-3.48 (m, 2H), 3.40-3.51 (m, 2H) , 6.50 (dd, J = 1.2,8.4Hz, 1H), 6.63 (d, J = 1.2Hz, 1H), 7.11 (br.s, 1H), 7.15 (s, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.78 (br.s, 1H), 8.37 (d, J = 7.5 Hz, 1H)

Example 149: 2- [1- (morpholin-4-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6 , 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, DMSO-d6) δ 0.82 (m, 2H), 1.15 (s, 6H), 1.39-1.45 (m, 2H), 2.00 (d, J = 9.3Hz, 2H), 2.39 (s , 3H), 3.03 (s, 2H), 3.10-3.15 (m, 5H), 3.43-3.52 (m, 2H), 3.61-3.64 (m, 4H), 6.67 (dd, J = 1.2,8.4Hz, 1H ), 6.80 (d, J = 1.2 Hz, 1H), 7.32 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.95 (br.s, 1H), 8.55 (d, J = 8.1 Hz , 1H)

Example 150: 4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- [1- (4-Fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.20 (m, 2H), 0.36 (m, 2H), 1.17 (s, 7H), 1.44 (m, 2H), 2.02 (m, 2H), 2.58 (m, 2H), 2.70 (d, J = 6.9 Hz, 2H), 2.98 (s, 2H), 3.56 (m, 3H), 6.67 (dd, J = 1.5 and 8.4 Hz, 1H), 6.73 (d, J = 1.2 Hz, 1H), 7.25 (brs, 1H), 7.29 (s, 1H), 7.50 (t, J = 8.7 and 9.0 Hz, 2H), 7.72 (d, J = 8.7 Hz, 1H), 7.83 (dd, J = 5.1 and 8.7 Hz, 2H), 7.92 (brs, 1H), 8.42 (d, J = 7.8 Hz, 1H).

Example 151: 2- [1- (1-Methyl-piperidin-4-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 1.35 (s, 6H), 1.65-1.74 (m, 2H), 1.81-1.97 (m, 4H), 2.04-2.09 (m, 4H), 2.27 (s, 3H ), 2.59 (s, 3H), 2.84-2.91 (m, 1H), 2,96 (m, 4H), 3.23 (td, J = 3.0,12.6Hz, 2H), 3.62 (m, 1H), 3.69- 3.73 (m, 2H), 5.19 (s, 1H), 5.71 (br.s, 1H), 6.54 (dd, J = 1.8, 8.4 Hz, 1H), 6.82 (d, J = 1.8 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1 H), 8.31 (d, J = 7.5 Hz, 1 H)

Example 152: 2- {1- [4- (4-Isopropyl-piperazin-1-yl-methyl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6 , 6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl ₃ , 300MHz) 1.07 (d, J = 6.5Hz, 6H), 1.33 (s, 6H), 1.76 (m, 2H), 2.07 (m, 2H), 2.53 (m, 7H), 2.59 (m, 4H), 2.72 (m, 3H), 2.93 (s, 2H), 3.46 (m, 1H), 3.53 (m, 2H), 3.60 (s, 2H), 5.17 (s, 1H), 5.80 ( brs, 2H), 6.50 (dd, J = 8.4 Hz, J = 1.9 Hz, 1H), 6.76 (d, J = 1.9 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.2 Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H), 8.16 (d, J = 7.5 Hz, 1H)

Example 153: 2- {1- [4- (morpholin-4-carbonyl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 1.33 (s, 6H), 1.78 (m, 2H), 2.07 (m, 2H), 2.53 (s, 3H), 2.93 (s, 2H), 2.99 (m, 2H) , 3.25 (m, 2H), 3.42 (m, 2H), 3.56 (m, 1H), 3.66 (m, 2H), 3.81 (m, 4H), 5.12 (s, 1H), 5.89 (brs, 2H), 6.51 (dd, J = 8.4Hz, J = 1.9Hz, 1H), 6.77 (d, J = 1.9Hz, 1H), 7.42 (d, J = 8.4Hz, 1H), 7.57 (d, J = 8.2Hz, 2H), 7.84 (d, J = 8.2 Hz, 2H), 8.24 (d, J = 7.6 Hz, 1H)

Example 154: 2- [1- (4-Isopropyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 1.06 (s, 6H), 1.08 (s, 3H), 1.37 (s, 6H), 2.10 (d, J = 10.8 Hz, 2H), 2.60 (m, 6H) , 2.71-2.80 (m, 1H), 2.99 (s, 2H), 3.15 (td, J = 2.7,12.6Hz, 2H), 3.30 (m, 4H), 3.63 (m, 3H), 5.32 (s, 1H ), 5.84 (br.s, 2H), 6.56 (d, J = 8.4 Hz, 1H), 6.85 (s, 1H), 7.49 (d, J = 8.4 Hz, 1H), 8.31 (d, J = 7.5 Hz , 1H)

Example 155: 4- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -cyclohexa-1-enecarboxylic acid

¹ H NMR (DMSO-d6, 300 MHz) 1.21 (s, 6H), 1.41 (m, 2H), 1.62 (m, 1H), 1.88-2.05 (m, 3H), 2.31 (m, 2H), 2.39 ( s, 3H), 2.42-2.61 (m, 3H), 2.95 (m, 2H), 3.03 (s, 2H), 3.33-3.44 (m, 3H), 3.60 (m, 1H), 6.64 (s, 1H) , 6.67 (d, J = 8.4 Hz, 1H), 6.79 (s, 1H), 7.29 (brs, 1H), 7.32 (d, J = 2.7 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H) , 7.95 (brs, 1 H), 8.51 (dd, J = 3.0 and 7.5 Hz, 1 H)

Example 156: 2- [1- (4-Piperidin-1-yl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo -4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO- d6 , 300MHz) 1.17 (s, 6H), 1.35 (m, 2H), 1.59 (s, 6H), 2.03 (m, 2H), 2.36 (s, 3H), 2.97 (s, 2H ), 3.48 (m, 3H), 6.62 (dd, J = 8.4Hz, J = 1.8Hz, 1H), 6.73 (d, J = 1.8Hz, 1H), 7.12 (d, J = 9.1Hz, 2H), 7.23 (brs, 1H), 7.29 (s, 1H), 7.47 (d, J = 8.9Hz, 2H), 7.72 (d, J = 8.6Hz, 1H), 7.90 (brs, 1H), 8.41 (d, J = 7.6 Hz, 1H)

Example 157: 2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6- Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO- d6 , 300MHz) 1.17 (s, 6H), 1.45 (m, 2H), 2.08 (m, 2H), 2.36 (s, 3H), 2.97 (s, 2H), 3.17 (d, J = 5.3 Hz, 2H), 3.46 (m, 3H), 6.62 (dd, J = 8.4 Hz, J = 1.8 Hz, 1H), 6.73 (d, J = 1.8 Hz, 1H), 7.09 (d, J = 9.1 Hz, 2H), 7.23 (brs, 1H), 7.29 (s, 1H), 7.53 (d, J = 9.0 Hz, 2H), 7.72 (d, J = 8.5 Hz, 1H), 7.71 (brs, 1H), 8.41 (d, J = 7.6 Hz, 1H)

Example 158: 2- [1- (4-Methyl- [1,4] diazepane-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl- 4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, chloroform-d): d 1.36 (s, 6H), 1.59-1.70 (m, 2H), 2.02-2.14 (m, 2H), 2.40 (s, 3H), 2.57 (s, 3H ), 2.67-2.71 (m, 4H), 2.97 (s, 2H), 3.02-3.10 (m, 2H), 3.50-3.58 (m, 6H), 3.64-3.66 (m, 2H), 3.71-3.75 (m , 1H), 5.31 (s, 1H), 5.76 (brs, 2H), 6.54-6.57 (dd, J = 8.4,1.8Hz, 1H), 6.83-6.84 (d, J = 1.8Hz, 1H), 7.46- 7.49 (d, J = 8.4 Hz, 1 H), 8.26-8.29 (d, J = 7.5 Hz, 1 H)

Example 159: 2- [1- (4-carbamoylmethyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo -4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, chloroform-d): d 1.36 (s, 6H), 1.83-1.87 (m, 1H), 2.03-2.17 (m, 2H), 2.57 (s, 3H), 2.62-2.65 (m , 4H), 2.97 (s, 2H), 3.08 (s, 2H), 3.11-3.20 (m, 2H), 3.28-3.31 (m, 4H), 3.57-3.64 (m, 3H), 3.72-3.77 (m , 1H), 5.47 (s, 1H), 5.73 (brs, 2H), 6.53-6.57 (dd, J = 8.4,1.8Hz, 1H), 6.85 (d, J = 1.8Hz, 1H), 6.85-6.91 ( m, 2H), 7.46-7.49 (d, J = 8.4 Hz, 1H), 8.32-8.34 (d, J = 7.5 Hz, 1H)

Example 160: 4- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -benzoic acid

¹ H NMR (MeOH-d4, 300 MHz) 1.25 (s, 6H), 1.54 (m, 2H), 2.07 (m, 1H), 2.40 (s, 3H), 2.69 (m, 2H), 2.97 (s, 2H), 3.43 (m, 1H), 3.58 (m, 2H), 6.60 (dd, J = 2.1 and 8.7 Hz, 1H), 6.75 (d, J = 1.8 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.1 Hz, 2H), 8.19 (d, J = 8.4 Hz, 1H)

Example 161: 2- {1- [4- (4-Isopropyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6 -Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO- d6 , 300 MHz) 0.99 (d, J = 6.5 Hz, 1H), 1.17 (s, 6H), 1.38 (m, 2H), 2.02 (m, 2H), 2.36 (s, 3H), 2.55 (m, 4H), 2.67 (sep, J = 6.5 Hz, 1H), 2.97 (s, 2H), 3.50 (m, 3H), 6.62 (dd, J = 8.4 Hz, J = 1.4 Hz, 1H), 6.73 (s, 1H), 7.07 (d, J = 9.0Hz, 2H), 7.24 (brs, 1H), 7.30 (s, 1H), 7.52 (d, J = 8.8Hz, 2H), 7.72 (d, J = 8.5Hz, 1H), 7.91 (brs, 1H), 8.41 (d, J = 7.5Hz, 1H)

Example 162: 4- (3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 1.35 (m, 10H), 1.70 (m, 2H), 2.07 (m, 2H), 2.32 (s, 3H), 2.46 (t, J = 4.9Hz, 4H), 2.96 (m, 4H), 3.12 (m, 2H), 3.29 (t, J = 5.1 Hz, 4H), 3.65 (m, 3H), 5.15 (s, 1H), 5.58 (brs, 2H), 6.59 (dd, J = 8.4Hz, J = 1.8Hz, 1H), 6.84 (d, J = 1.9Hz, 1H), 7.48 (d, J = 8.4Hz, 1H), 8.31 (d, J = 7.6Hz, 1H)

Example 163: 2- {1- [4- (3-Methyl- [1,3] diazepan-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3 , 6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 1.18 (m, 2H), 1.33 (s, 6H), 2.04 (m, 4H), 2.39 (s, 3H), 2.54 (s, 3H), 2.59 (m, 4H) , 2.73 (m, 2H), 2.93 (s, 2H), 3.52 (m, 3H), 3.64 (m, 4H), 5.20 (s, 1H), 5.75 (brs, 2H), 6.46 (dd, J = 8.4 Hz, J = 1.8Hz, 1H), 6.69 (d, J = 9.1Hz, 2H), 6.75 (d, J = 1.8Hz, 1H), 7.42 (d, J = 8.4Hz, 1H), 7.56 (d, J = 9.0 Hz, 2H), 8.14 (d, J = 7.5 Hz, 1H),

Example 164: 4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.19 (m, 2H), 0.36 (m, 2H), 1.17 (s, 6H), 1.23 (m, 1H), 1.41 (m, 2H), 2.01 (m, 2H), 2.22 (s, 3H), 2.43 (m, 6H), 2.70 (d, J = 6.9 Hz, 2H), 2.98 (s, 2H), 3.31 (m, 4H), 3.42 (m, 2H), 3.48 (m, 2H), 6.67 (d, J = 8.4 Hz, 1H), 6.73 (s, 1H), 7.07 (d, J = 9.0 Hz, 2H), 7.14 (brs, 1H), 7.29 (s, 1H) ), 7.51 (d, J = 8.7 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.92 (brs, 1H), 8.40 (d, J = 7.5 Hz, 1H).

Example 165: 4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (1-Methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 1.21 (s, 6H), 1.41 (m, 2H), 2.00 (m, 2H), 2.74 (m, 2H), 3.04 (s, 2H), 3.40 (m, 1H), 3.49 (m, 2H), 3.71 (s, 3H), 6.71 (dd, J = 1.8 and 8.4 Hz, 1H), 6.87 (s, 1H), 7.35 (brs, 1H), 7.74 (s, 1H ), 7.77 (d, J = 8.4 Hz, 1H), 7.83 (s, 2H), 7.99 (brs, 1H), 8.43 (d, J = 7.6 Hz, 1H)

Example 166: 4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- [1- (1-Methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 0.21 (m, 2H), 0.37 (m, 2H), 1.19 (m, 7H), 1.42 (m, 2H), 2.01 (m, 2H), 2.71 (d, J = 6.9 Hz, 2H), 2.77 (m, 2H), 3.01 (s, 2H), 3.49 (m, 3H), 3.71 (s, 3H), 6.68 (dd, J = 1.5 and 8.4 Hz, 1H), 6.76 (d, J = 1.5 Hz, 1H), 7.26 (brs, 1H), 7.29 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.83 (s, 2H), 7.93 (brs, 1H) ), 8.44 (d, J = 7.5 Hz, 1H)

Example 167: 2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,7,7- Trimethyl-5-oxo-4a, 5,6,7,8,8a-hexahydro-4H-pyrido [4,3-c] pyridazin-1-yl) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 1.22 (s, 6H), 1.84-1.88 (m, 1H), 2.05 (s, 6H), 2.32 (s, 2H), 2.40 (s, 3H), 2.61 ( m, 6H), 3.04 (s, 2H), 3.29 (m, 1H), 3.90 (t, J = 4.5Hz, 4H), 3.59-3.64 (m, 2H), 3.73-3.77 (m, 1H), 5.13 (s, 1H), 5.62 (br.s, 1H), 6.41-6.45 (m, 2H), 6.93 (d, J = 8.7Hz, 2H), 7.36 (d, J = 8.4Hz, 1H), 7.62 ( d, J = 8.7 Hz, 2H), 8.09 (d, J = 7.2 Hz, 1H)

Example 168 4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide

¹ H NMR (DMSO-d6, 300 MHz) 1.19 (s, 6H), 1.39 (m, 2H), 2.01 (m, 2H), 2.22 (s, 3H), 2.43 (m, 6H), 3.01 (s, 2H), 3.31 (m, 4H), 3.41 (m, 1H), 3.48 (m, 2H), 6.70 (dd, J = 1.5 and 8.4 Hz, 1H), 6.83 (d, J = 1.5 Hz, 1H), 7.07 (d, J = 9.3 Hz, 2H), 7.34 (brs, 1), 7.51 (d, J = 9.0 Hz, 2H), 7.74 (d, J = 3.0 Hz, 1H), 7.77 (s, 1), 7.99 (brs, 1), 8.40 (d, J = 7.8 Hz, 1H).

Example 169 2- [1- (1-Methyl-piperidin-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, chloroform-d): d 1.35 (s, 6H), 1.76-1.93 (m, 6H), 2.06-2.14 (m, 4H), 2.32 (s, 3H), 2.56 (s, 3H ), 2.80-2.84 (d, J = 11.7 Hz, 1H), 2.96 (s, 2H), 3.14-3.25 (m, 4H), 3.58-3.73 (m, 3H), 5.36 (m, 1H), 5.80- 5.91 (s, 2H), 6.51-6.55 (dd, J = 8.4,1.8Hz, 1H), 6.83-6.84 (d, J = 1.8Hz, 1H), 7.46-7.49 (d, J = 8.4Hz, 1H) , 8.31-8.33 (d, J = 7.5 Hz, 1H)

Example 170: 2- {1- [4- (4-ethyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6- Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (DMSO- d6 , 300 MHz) 1.03 (t, J = 7.3 Hz, 3H), 1.17 (s, 6H), 1.38 (m, 2H), 1.98 (m, 2H), 2.37 (m, 5H), 2.97 (s, 2H), 3.50 (m, 3H), 6.62 (dd, J = 8.4Hz, J = 1.7Hz, 1H), 6.73 (d, J = 1.7Hz, 1H), 7.08 (d, J = 9.0 Hz, 2H), 7.25 (brs, 1H), 7.31 (s, 1H), 7.52 (d, J = 8.9Hz, 2H), 7.76 (d, J = 8.6Hz, 1H), 7.91 (brs, 1H), 8.41 (d, J = 7.6 Hz, 1H)

Example 171: 2- {1- [4- (4-hydroxy-piperidin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6, 6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, CDCl ₃ ) δ 1.17 (s, 6H), 1.36-1.46 (m, 4H), 1.74-1.82 (m, 3H), 2.03 (m, 4H), 2.37 (s, 3H), 2.98 (s, 2H), 3.05 (td, J = 3.0,13.2Hz, 2H), 3.32 (s, 3H), 3.43-3.51 (m, 4H), 3.58-3.62 (m, 2H), 3.70-3.74 ( m, 3H), 4.77 (d , J = 4.2Hz, 1H), 6.64 (dd, J = 1.2,8.4Hz, 1H), 6.74 (d, J = 1.2Hz, 1H), 7.06 (d, J = 9.0 Hz, 2H), 7.25 (br.s, 1H), 7.31 (s, 1H), 7.48 (d, J = 9.0Hz, 2H), 7.70 (d, J = 8.4Hz, 1H), 7.92 (br.s , 1H), 8.41 (d, J = 7.5Hz, 1H)

Example 172: 2- [1- (1-cyclopropylmethyl-piperidine-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, chloroform-d): d 0.08-0.13 (m, 2H), 0.50-0.56 (m, 2H), 0.78-0.92 (m, 1H), 1.35 (s, 6H), 1.50-1.72 (m, 4H), 1.78-1.97 (m, 4H), 2.04-2.18 (m, 4H), 2.56 (s, 3H), 2.95 (s, 2H), 3.00-3.04 (m, 1H), 3.16-3.28 (m, 3H), 3.40-3.56 (m, 1H), 3.58-3.73 (m, 3H), 5.45 (s, 1H), 5.93 (brs, 2H), 6.50-6.53 (dd, J = 8.4,1.8 Hz , 1H), 6.83-6.84 (d, J = 1.8Hz, 1H), 7.46-7.49 (d, J = 8.4Hz, 1H), 8.31-8.33 (d, J = 7.5Hz, 1H)

Example 173: 2- [1- (1-Methyl-piperidin-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide

¹ H NMR (300 MHz, chloroform-d): d 1.35 (s, 6H), 1.48-1.64 (m, 3H), 1.81-1.94 (m, 3H), 2.06-2.13 (m, 4H), 2.32 (s , 3H), 2.57 (s, 3H), 2.80-2.83 (d, J = 11.1 Hz, 1H), 2.96 (s, 2H), 3.14-3.25 (m, 4H), 3.62-3.73 (m, 3H), 5.27 (s, 1H), 5.80 (brs, 2H), 6.52-6.55 (dd, J = 8.4,1.8Hz, 1H), 6.83-6.84 (d, J = 1.8Hz, 1H), 7.46-7.49 (d, J = 8.4 Hz, 1H), 8.31-8.34 (d, J = 7.8Hz, 1H)

Example 174: 2- (1,2,2,6,6-pentamethyl-piperidin-4-yl-amino) -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl-benzamide

¹ H NMR (CDCl ₃ , 300 MHz) 1.13 (s, 6H), 1.18 (s, 6H), 1.35 (s, 6H), 1.471 (m, 2H), 1.97 (m, 2H), 2.28 (s, 3H) , 2.56 (s, 3H), 3.01 (s, 2H), 3.64 (m, 1H), 5.22 (s, 1H), 5.69 (brs, 2H), 6.71 (m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 6.9 Hz, 1H)

Test Example 1 Test of Inhibitory Activity of HSP90 of Compound 1

It is reported that the compound of formula 1 of the present invention is a comparative compound SNX-2112 (now a compound being developed in clinical phase 1, and is most effective as a small molecule) at the ATP attachment site of the humanized Hsp90α protein. In vitro HSP90 inhibition effect by Fluoresence Polarization assay was 0.2 μM and cell level cell proliferation inhibitory activity was 0.1-0.001 μM, Bioorganic & Medicinal Chemistry Letters, Volume 18, Issue 12, 15 June 2008, Pages 3517-3521) Fluoresence Polarization assay was performed to compare how well binding. To carry out this experiment, we used an 86.8 kDa human human Hsp90 α protein (concentration 1 mg / ml) purchased from Abcam (cat. No. Ab48801). Fluorescently attached (used by direct synthesis) was used. The reaction solution (buffer, buffer) used in the experiment was prepared by adding 100 mM Tris-Hcl (pH 7.4), 20 mM KCl, 6 mM MgCl 2, and 5 µg / ml BSA in sterile tertiary distilled water. All experiments were conducted twice, and the experimental method is as follows.

The comparative compound to be tested and the compound of formula 1 (25 mM stock) of the present invention were prepared by diluting in 100% DMSO in accordance with the following criteria. First, the activity of the compound was confirmed at concentrations of 0, 1, 15, and 30 uM, and when the IC ₅₀ value was calculated to be 15 uM or less, the second experiment was conducted again at 0, 1, 5, 10, and 15 uM. Particularly, in the first experiment, the second experiment was conducted at low concentrations of 0, 100, 500, 1000, and 2000 nM for the compound having a very good value of IC ₅₀ or less. 1 μl of the compound diluted in 100% DMSO was added to each well of a 96-well black plate.

Into 100 μl of reaction volume per well, 3 μg of humanized Hsp90 α protein and 10 nM fluorescent probe should be added. Therefore, 30 μl and 2.5 μl of humanized Hsp90 α protein and fluorescent label (probe) are added to 1 μl of the buffer volume. The volume of the reaction mixture (mixture) required for the experiment was made and thoroughly mixed through a vortex, and then 100 μl was added to each well of a 96-well black plate using eppendorf's repeater ^® plus pippette. And the plate was fixed to a shaker (shaker) at 37 ℃, room temperature and reacted for about 10 minutes. The fluorescence intensity of each well was measured on the plate after the reaction by PerkinElmer's ENVISION (excitation 485, emission 535). By analyzing the polarization value (mP value) calculated through the program, the concentration of the compound that inhibits 50% of the fluorescent activity is shown in Table 2 by expressing the IC ₅₀ value.

Test Example 2: Determination of the effect of inhibiting cell proliferation by the inhibitory effect of HSP90 of the compound of Formula 1

The following analysis was performed using MV4-11 cells (ATCC, CRL-9591), a human acute myeloid leukemia cell line, and SK-BR3 cells, a breast cancer cell line.

MV4-11 cells were seeded in 96 well plates containing IMEM (Iscove's Modified Eagle Medium) medium with 50 μl of 3 × 10 ⁴ cells in each well, followed by 24 hours at 5% CO ₂ and 37 ° C. Incubated. To find the starting point for cell proliferation prior to compound treatment, the same amount as the medium was obtained using a Luminescent Cell Viability Assay (CellTiter-Glo ^® Promega, G7573), which measures the level of ATP present in cells. Each well was dispensed. After shaking the 96-well plate sufficiently for about 2 minutes, and waiting for 10 minutes to avoid direct sunlight at room temperature, the results were confirmed by using a luminescence meter mounted on ENVISION (PerkinElmer). Subsequently, each well was treated with a compound of formula 1 and a comparative compound SNX-2112 at step concentrations of 0.00001, 0.0001, 0.001, 0.01, 0.1, 1, 10 and 100 μM, respectively, in different plates, It was not treated with the compound either. Each cell was then incubated for 72 hours.

 Cultured cells were dispensed in the same amount as the media contained in each well using luminescent cell viability assays. After shaking the 96-well plate sufficiently for about 2 minutes, and waiting for 10 minutes to avoid direct sunlight at room temperature, the results were confirmed using a luminescence meter mounted on ENVISION (PerkinElmer).

Using the breast cancer cell line SK-BR3 cells, the analysis was performed in the same manner as the above method.

Inhibition of cell proliferation according to the treatment concentration of each compound was calculated on the basis of luminescence at the start of cell proliferation before treatment with the control cells without the compound and the compound, wherein 50% of the cells inhibit the proliferation of cancer cells. The concentration of the compound is shown in Table 2 as GI ₅₀ (μM).

Claims (9)

A compound represented by the following formula (1), a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof:
[Formula 1]

Where
D is C or N,
R1 is hydrogen, halogen, CN, NO ₂ , guanidino, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, trihalo (C1-C4) Alkoxy, trihalo (C 1 -C 4) alkyl,-(CH ₂ ) _0-6 -R ^a , -C2-C6 alkenyl-R ^a ,-(CH ₂ ) _0-6 -OR ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) R ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) OR ^a ,-(CH ₂ ) _{0 ~ 6} -S (O) R ^a ,-(CH ₂ ) _{0 6-} SO ₂ R ^a , -OC (O) R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , -NHC (O) R ^a , -C (O) NR ^a R ^b , -NHC (S) R ^a , -C (S) NR ^a R ^b , -SR ^a , -NHSO ₂ R ^a , -SO ₂ NR ^a R ^b , -OSO ₂ R ^a , or -SO ₂ OR ^a , wherein R ^a and R ^b are each independently hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, COOH Substituted with one or more substituents selected from the group consisting of: -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Unsubstituted C1-C8 alkyl;
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C3-C8 cycloalkyl or C3-C8 heterocycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of groups; or
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with one or more substituents selected from the group consisting of groups;
Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;
R2 is hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2- C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, (C1-C4) alkyl substituted with C3-C8 heterocycloalkyl group, trihalo ( C 1 -C 4) alkoxy, trihalo (C 1 -C 4) alkyl, C 1 -C 4 dialkylamino, amines substituted by straight or branched C 1 -C 8 alkyl groups, amines substituted by C 3 -C 8 cycloalkyl groups, C 1 -C 6 Alkylamino (C1-C4) alkyl, C1-C6 dialkylamino (C1-C8) alkyl, C1-C6 alkyleneimino (C1-C4) alkyl group, or-(CH ₂ ) _0-6 -NR ^a , Where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C3-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, One or more substituents selected from the group consisting of -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl A substituted or unsubstituted C6-C18 aryl or C3-C18 heteroaryl group;
R3 is hydrogen; halogen; CN; NO ₂ ; OH; -SH; -COOH; Formyl; Guanidino; -CONH ₂ ; Straight or branched C1-C8 alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C1-C8 alkoxy; Straight or branched C1-C8 alkyl containing one or more hetero atoms; -(CH ₂ ) _0-6 -R ^a ; -(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C2-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, One or more selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl groups C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with a substituent;
R4 and R5 are each independently hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 Alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, trihalo (C1-C4) alkoxy, trihalo (C1 -C4) alkyl, amine substituted with straight or branched C1-C8 alkyl group, or amine substituted with C3-C8 cycloalkyl group;
In the above, the alkyl group means a branched or branched alkyl group, and each R ^C may be independently selected when there are a plurality of R ^Cs in a molecule. The method according to claim 1,
R 1 is hydrogen, halogen, CN, NO ₂ , straight or branched C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkoxy,-(CH ₂ ) _0-6 -R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , wherein R ^a and R ^b are each independently hydrogen; Wherein R ^a and R ^b are each independently hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl;
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C3-C8 cycloalkyl or C3-C8 heterocycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of groups; or
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 From the group consisting of -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl group C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with one or more substituents selected;
Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;
R2 is substituted with a hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkyl group (C1- C4) alkyl, (C1-C4) alkyl substituted by C3-C8 heterocycloalkyl group, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl, C1-C4 dialkylamino, straight or branched Amines substituted with C1-C8 alkyl groups in the chain, amines substituted with C3-C8 cycloalkyl groups, C1-C6 alkylamino (C1-C4) alkyl, C1-C6 dialkylamino (C1-C8) alkyl, C1-C6 alkyl alkylene butylimino (C1 ~ C4) group, or - a _{(CH 2) 0 ~ 6 -NR} a, where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl;
R3 is hydrogen; halogen; Straight or branched C1-C8 alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C1-C8 alkoxy; Straight or branched C1-C8 alkyl containing one or more hetero atoms; NO ₂ ; -(CH ₂ ) _0-6 -R ^a ; -(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl unsubstituted or substituted with one or more C1-C4 alkyl groups; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- C3-C8 cycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl, or C3-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, C6 ~ C18 unsubstituted or substituted with one or more substituents selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl Aryl or a C3-C18 heteroaryl group;
R4 and R5 are each independently hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkyl groups Substituted (C1-C4) alkyl, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl, amines substituted with straight or branched C1-C8 alkyl groups, or C3-C8 cycloalkyl groups A compound represented by the formula (1), a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof, which is a substituted amine. The method according to claim 2,
R1 is hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, trifluoromethoxy, trifluoromethyl,-(CH ₂ ) _0-6 -R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , wherein R ^a and R ^b are each independently hydrogen; C1-C8 alkyl unsubstituted or substituted with one or more substituents selected from C1-C4 alkylamino, or C1-C4 dialkylamino;
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

A C3-C8 cycloalkyl or C3-C8 heterocycloalkyl group unsubstituted or substituted with one or more substituents selected from the group consisting of
Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;
R2 is hydrogen, halogen, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl group substituted with (C1-C4) alkyl, C3 (C1-C4) alkyl, trifluoromethoxy, trifluoromethyl, C1-C4 dialkylamino, C1-C6 alkylamino (C1-C4) alkyl, C1-C6 dialkylamino substituted with a -C8 heterocycloalkyl group (C1 ~ C8) alkyl, C1-C6-alkylene-butylimino (C1 ~ C4) alkyl, or - a _{(CH 2) 0 ~ 6 -NR} a, where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- C 1 -C 8 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of COOH, —COO (C 1 -C 4 alkyl), —CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl; Is;
R3 is hydrogen; halogen; Straight or branched C1-C8 alkyl; NO ₂ ; C2-C8 alkenyl; C2-C8 alkynyl; -(CH ₂ ) _0-6 -R ^a ; -(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl unsubstituted or substituted with one or more C1-C4 alkyl groups; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- C3-C8 cycloalkyl or C3 unsubstituted or substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo trifluoromethoxy, and trifluoromethyl -C8 heterocycloalkyl; Or halogen, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, C6 ~ C18 unsubstituted or substituted with one or more substituents selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trifluoromethoxy, and trifluoromethyl Aryl or a C3-C18 heteroaryl group;
R 4 and R 5 are each independently substituted with hydrogen, straight or branched C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl group (C 1 -C 4) A compound represented by the formula (1), a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof, which is an alkyl, trifluoromethoxy, or trifluoromethyl group. The method of claim 3, wherein the compound of Formula 1
2- (4-hydroxycyclohexylamino) -4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl] -benzamide,
2-bromo-4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine-1 -Yl] -benzamide,
2-bromo-4- (3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide,
2- (4-hydroxycyclohexylamino) -4- (3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) Benzamide,
4- (3,5-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxycyclohexyl Amino) -benzamide,
2-bromo-4- (5-ethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide,
2-Bromo-4- (5-isopropyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benzamide ,
2-Bromo-4- (5-cyclopropylmethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -benz amides,
4- (5-cyclopropylmethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydrate Hydroxy-cyclohexylamino) -benzamide,
2- (4-hydroxycyclohexylamino) -4- (5-isopropyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine -1-yl) -benzamide,
4- (5-ethyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxy- Cyclohexylamino) -benzamide,
4- (5-benzyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxy- Cyclohexylamino) -benzamide,
2- (4-hydroxycyclohexylamino) -4- (3-methyl-4-oxo-5-thiophen-3-yl-methyl-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl) -benzamide,
4- (5-butyl-3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxy- Cyclohexylamino) -benzamide,
2- (4-hydroxycyclohexylamino) -4- (3-methyl-5-octyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine- 1-yl) -benzamide,
4- [5- (4-fluoro-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -2 -(4-hydroxycyclohexylamino) -benzamide,
2- (4-hydroxycyclohexylamino) -4- [5- (3-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl] -benzamide,
2- (4-hydroxycyclohexylamino) -4- [3-methyl-4-oxo-5- (4-trifluoromethoxy-benzyl) -4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -benzamide,
2- (4-hydroxycyclohexylamino) -4- [5- (2-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3 , 2-c] pyridin-1-yl] -benzamide,
4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -2 -(2-morpholin-4-yl-ethylamino) -benzamide,
2- (2-dimethylamino-ethylamino) -4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3, 2-c] pyridin-1-yl] -benzamide,
4- [5- (4-methoxy-benzyl) -3-methyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl] -2 -[3- (2-oxo-pyrrolidin-1-yl) -propylamino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [2- (1-oxy-pyrrolidin-1-yl) -ethylamino] -benzamide,
2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine- 1-yl) -benzamide,
2- (4-hydroxycyclohexylamino) -4- (3,5,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c ] Pyridin-1-yl) -benzamide,
4- (5-ethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4 -Hydroxycyclohexylamino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (3- (trifluoromethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4,3-c ] Pyridin-1-yl) benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (3- (trifluoromethyl) -4,5,6,7-tetrahydro-5,6,6-trimethyl-4-oxopyrazolo [4,3 -c] pyridin-1-yl) benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (5- (cyclopropylmethyl) -3- (trifluoromethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxo Pyrazolo [4,3-c] pyridin-1-yl) benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4,3-c] Pyridin-1-yl) benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -4,5,6,7-tetrahydro-5,6,6-trimethyl-4-oxopyrazolo [4,3- c] pyridin-1-yl) benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (3- (cyclopropylmethyl) -5-ethyl-4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4, 3-c] pyridin-1-yl) benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (4,5,6,7-tetrahydro-3-isobutyl-6,6-dimethyl-4-oxopyrazolo [4,3-c] pyridine-1 Benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (3,5-bis (cyclopropylmethyl) -4,5,6,7-tetrahydro-6,6-dimethyl-4-oxopyrazolo [4,3 -c] pyridin-1-yl) benzamide,
2-( Trance -4-hydroxycyclohexylamino) -4- (5-allyl-4,5,6,7-tetrahydro-3-isobutyl-6,6-dimethyl-4-oxopyrazolo [4,3-c ] Pyridin-1-yl) benzamide,
4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- ( 2-morpholin-4-yl-ethylamino) -benzamide,
2- [3- (2-oxo-pyrrolidin-1-yl) -propylamino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-py Rolo [3,2-c] pyridin-1-yl) -benzamide,
4- (5-ethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,
4- (5-cyclopropylmethyl-3-isobutyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,
4- (5-Cyclopropylmethyl-3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- (4-hydroxycyclohexylamino) -benzamide,
4- (3,5-bis-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl)- 2- (2-morpholin-4-yl-ethylamino) -benzamide,
2- (4-hydroxycyclohexylamino) -4- [3,6,6-trimethyl-5- (2-methyl-allyl) -4-oxo-4,5,6,7-tetrahydro-pyra Zolo [4,3-c] pyridin-1-yl] -benzamide,
2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine- 1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (2-morpholin-4-yl-ethylamino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [3- (2-oxo-pyrrolidin-1-yl) -propylamino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (2-dimethylamino-ethylamino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (2-pyrrolidin-1-yl-ethylamino) -benzamide,
Aminoacetic acid 4- [2-carbamoyl-5- (3,5,6,6-tetramethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridine- 1-yl) -phenylamino] -cyclohexyl ester,
4- (6,6-dimethyl-3-methylaminomethyl-5-nitro-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl)- 2- (4-hydroxycyclohexylamino) -benzamide,
4- (6,6-dimethyl-5-methylamino-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,
4- (5-cyclopropylamino-6,6-dimethyl-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl ) -2- (4-hydroxycyclohexylamino) -benzamide,
4- (3-Aziridin-1-yl-methyl-5-cyclopropylamino-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] Pyridin-1-yl) -2- (4-hydroxycyclohexylamino) -benzamide,
4- (5-cyclopropylamino-6,6-dimethyl-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrrolo [3,2-c] pyridin-1-yl ) -2- (4-hydroxy-piperidin-1-yl-methyl) -benzamide,
4- (5-cyclopropylamino-6,6-dimethyl-3-methylaminomethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl ) -2- (4-hydroxy-piperazin-1-yl-methyl) -benzamide,
2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-4-oxo-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3- c] pyridin-1-yl) benzamide,
2- (4-hydroxycyclohexylamino) -4- (3,6,6-trimethyl-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridine- 1-yl) benzamide,
2-((4-acetylpiperazin-1-yl) methyl) -4- (3,6,6-trimethyl-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3 -c] pyridin-1-yl) benzamide,
2-((4-acetylpiperazin-1-yl) methyl) -4- (3,6,6-trimethyl-4-oxo-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl) benzamide,
2-((4-acetylpiperazin-1-yl) methyl) -4- (3,6,6-trimethyl-5-pivaloyl-4,5,6,7-tetrahydropyrazolo [4,3 -c] pyridin-1-yl) benzamide,
2- (1-acetylpiperidin-4-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl-4-oxo Pyrazole [4,3-c] pyridin-1-yl) benzamide,
(S) -tert-butyl 3- (2-carbamoyl-5- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) phenylamino) pyrrolidine-1-carboxylate,
2-((S) -1-acetylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl -4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,
2-((S) -1-benzoylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6-trimethyl -4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,
2-((S) -1-phenylsulfonylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6- Trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,
2-((S) -1-cyclopropylcarbonylpyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3,6,6 -Trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,
2-((S) -1- (2-tert-butyloxycarbonylaminoacetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7 Tetrahydro-3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,
2-((S) -1- (2-aminoacetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro-3, 6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide hydrochloride,
2-((S) -1- (2- (dimethylamino) acetyl) pyrrolidin-3-yl-amino) -4- (5- (cyclopropylmethyl) -4,5,6,7-tetrahydro -3,6,6-trimethyl-4-oxopyrazole [4,3-c] pyridin-1-yl) benzamide,
5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-diethylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide,
2- [1- (2-cyclopropylamino-acetyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- (1-acetyl-pyrrolidin-3-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro- Pyrazolo4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-methanesulfonyl-pyrrolidin-3-yl-amino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (3-Methyl-butyryl) -pyrrolidin-3-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-ethylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-isobutylamino-acetyl) -pyrrolidin-3-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-piperidin-1-yl-acetyl) -pyrrolidin-3-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Morpholin-4-yl-acetyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Isopropylamino-acetyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Pyrrolidin-1-yl-acetyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-ethanesulfonyl-pyrrolidin-3-yl-amino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-dimethylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide,
2- [1- (Boc-sulfamoyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6, 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (Propan-2-sulfonyl) -pyrrolidin-3-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-sulfamoyl-pyrrolidin-3-yl-amino) -benzamide,
2-bromo-4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -benzamide,
2- [1- (2-cyclobutylamino-acetyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- (1-Carbamoylmethyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Oxo-propyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Oxo-2-phenyl-ethyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-formyl-piperidin-4-yl-amino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Oxo-butyl) -piperidin-4-yl-amino] -benzamide,
3- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine -1-yl) -phenylamino] -pyrrolidine-1-carboxylic acid tert-butyl ester,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-isopropylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide,
2- (1-Chloromethanesulfonyl-pyrrolidin-3-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-ethanesulfonyl-piperidin-4-yl-amino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (Propan-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,
Acetic acid 2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3 -c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -ethyl ester,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-hydroxy-ethyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-dimethylsulfamoyl-pyrrolidin-3-yl-amino) -benzamide,
2- [1- (butane-1-sulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (2-Methyl-propane-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,
{4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] Pyridin-1-yl) -phenylamino] -piperidin-1-yl} -acetic acid methyl ester,
2- [1- (1-Carbamoyl-ethyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-isopropylsulfamoyl-piperidin-4-yl-amino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-cyclopropylsulfamoyl-piperidin-4-yl-amino) -benzamide,
2- (1-Chloromethanesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -propionic acid methyl ester,
2- (1-Boc-1'-benzylsulfamoyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- (1-benzylsulfamoyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (2- (cyclopropylamino-acetyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (1-Methyl-2-oxo-propyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (1-dimethylcarbamoylmethyl-piperidin-4-yl-amino) -benzamide,
4- [2-carbamoyl-5- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4, 3-c] pyridin-1-yl) -phenylamino] -piperidine-1-carboxylic acid tert-butyl ester,
4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -2- (piperidin-4-yl-amino) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (1-dimethylcarbamoyl-ethyl) -piperidin-4-yl-amino] -benzamide,
2- [1- (Cyclopropylmethyl-sulfamoyl) -pyrrolidin-3-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamidetetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (4-cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
(2- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyra Zolo [4,3-c] pyridin-1-yl) -phenylamino] -piperidin-1-yl} -2-oxo-ethyl) -carbamic acid tert-butyl ester,
2- [1- (2-cyclopropylamino-acetyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoro Methyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,
2- (1- (4-Amido-benzenesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (4-Aminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (1-Methyl-2-morpholin-4-yl-2-oxo-ethyl) -piperidin-4-yl-amino] -benzamide,
2- [1- (3-cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- (1- (3-Amido-benzenesulfonyl-piperidin-4-yl-amino) -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4-methanesulfonylamino-cyclohexylamino) -benzamide,
2- (4-acetylamino-cyclohexylamino) -4- (5-cyclopropyl methyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4, 3-c] pyridin-1-yl) -benzamide,
2- [1- (3-aminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (2-cyano-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (3-Cyano-4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (3-Aminomethyl-4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (4-Bromomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4 , 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Dimethylaminomethyl-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Piperidin-1-yl-methyl-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [4- (4-Fluoro-benzenesulfonylamino) -cyclohexylamino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Isopropyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Methyl- [1,4] diazepan-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,
4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl}-[1,4] diazepane-1-carboxylic acid tert-butyl ester,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (morpholin-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,
N- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -cyclohexyl} -isonicotinamide,
2- [1- (4-Fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7- Tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
N- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -cyclohexyl} -nicotinamide,
4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -benzoic acid,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (4-Ethoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,
2- [1- (3-Cyano-4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -4- (5-cyclopropylmethyl-3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (3-Amido, 4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- (3-acetic acid, 4-methoxy-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,
4- {4- [2-carbamoyl-5- (5-cyclopropylmethyl-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3- c] pyridin-1-yl) -phenylamino] -piperidine-1-sulfonyl} -cyclohexa-1-enecarboxylic acid,
4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -2- [1- (1-methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,
4- (5-cyclopropylmethyl-6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -2- {1- [4- (4-methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide,
4- (3-dimethylaminomethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- (4 -Hydroxycyclohexylamino) -benzamide,
2- (1-benzenesulfonyl-piperidin-4-yl-amino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4 , 3-c] pyridin-1-yl) -benzamide,
2- [4- (4-Fluoro-benzenesulfonylamino) -cyclohexylamino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
N- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -phenylamino] -cyclohexyl} -isonicotinamide,
2- [1- (imidazol-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6 , 7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (morpholin-4-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetra Hydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1 -(4-fluoro-benzenesulfonyl) -piperidin-4-yl-amino] -benzamide,
2- [1- (1-Methyl-piperidin-4-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- {1- [4- (4-Isopropyl-piperazin-1-yl-methyl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl -4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- {1- [4- (morpholin-4-carbonyl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4-oxo-4 , 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (4-Isopropyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -phenylamino] -piperidine-1-sulfonyl} -cyclohexa-1-enecarboxylic acid,
2- [1- (4-Piperidin-1-yl-benzenesulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (4-Methyl- [1,4] diazepane-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo- 4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (4-Carbamoylmethyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5 , 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- {4- [2-carbamoyl-5- (3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridine-1- Yl) -phenylamino] -piperidine-1-sulfonyl} -benzoic acid,
2- {1- [4- (4-Isopropyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4 Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (3-ethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1- ( 4-Methyl-piperazin-1-sulfonyl) -piperidin-4-yl-amino] -benzamide,
2- {1- [4- (3-Methyl- [1,3] diazepan-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6 -Trimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- {1 -[4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide,
4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [ 1- (1-Methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,
4- (3-cyclopropylmethyl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- [1 -(1-methyl-1H-imidazol-4-sulfonyl) -piperidin-4-yl-amino] -benzamide,
2- {1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,7,7-trimethyl-5- Oxo-4a, 5,6,7,8,8a-hexahydro-4H-pyrido [4,3-c] pyridazin-1-yl) -benzamide,
4- (6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -2- { 1- [4- (4-Methyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -benzamide,
2- [1- (1-Methyl-piperidin-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- {1- [4- (4-Ethyl-piperazin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl-4- Oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- {1- [4- (4-Hydroxy-piperidin-1-yl) -benzenesulfonyl] -piperidin-4-yl-amino} -4- (3,6,6-trimethyl- 4-oxo-4,5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (1-cyclopropylmethyl-piperidine-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4, 5,6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide,
2- [1- (1-Methyl-piperidin-3-sulfonyl) -piperidin-4-yl-amino] -4- (3,6,6-trimethyl-4-oxo-4,5, 6,7-tetrahydro-pyrazolo [4,3-c] pyridin-1-yl) -benzamide, and
2- (1,2,2,6,6-pentamethyl-piperidin-4-yl-amino) -4- (3,6,6-trimethyl-4-oxo-4,5,6,7- A compound represented by formula (1), a pharmaceutically acceptable salt, hydrate, solvate thereof, wherein the compound is selected from the group consisting of tetrahydro-pyrazolo [4,3-c] pyridin-1-yl-benzamide Isomers. Treating a disease associated with the activation of HSP90 comprising a compound of formula 1 as defined in any one of claims 1 to 4, a pharmaceutically acceptable salt, hydrate, solvate or isomer thereof, and a pharmaceutically acceptable carrier. Pharmaceutical composition for. The method of claim 5, wherein the disease associated with activation of HSP90 is cancer, carcinoma and inflammatory disease related pain; headache; fever; asthma; bronchitis; Tendinitis; Bursitis; eczema; psoriasis; dermatitis; Autoimmune inflammation; Crohn's disease; Hodgkin's disease; diabetes; Rheumatic fever; Ischemia; Neurodegenerative diseases (senile dementia, Parkinson's disease, Kennedy's disease with muscle degeneration associated with polyQ disease); Alzheimer's disease; CNS disorders; And pharmaceutical composition, characterized in that any one of immune diseases. Preparing a compound of Chemical Formula 5 by reacting a compound of Chemical Formula 3 with a compound of Chemical Formula 4 under a base;
Method for preparing a compound represented by the following formula 2 comprising the step of hydrolyzing the nitrile (CN) group of the compound of formula 5:
(2)

(3)

[Chemical Formula 4]
R3-Y

[Chemical Formula 5]

In Chemical Formulas 3 to 5,
D is C or N,
X is hydrogen, halogen, CN, NO ₂ , guanidino, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, trihalo (C1-C4) Alkoxy, trihalo (C 1 -C 4) alkyl,-(CH ₂ ) _0-6 -R ^a , -C2-C6 alkenyl-R ^a ,-(CH ₂ ) _0-6 -OR ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) R ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) OR ^a ,-(CH ₂ ) _{0 ~ 6} -S (O) R ^a ,-(CH ₂ ) _{0 6-} SO ₂ R ^a , -OC (O) R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , -NHC (O) R ^a , -C (O) NR ^a R ^b , -NHC (S) R ^a , -C (S) NR ^a R ^b , -SR ^a , -NHSO ₂ R ^a , -SO ₂ NR ^a R ^b , -OSO ₂ R ^a , or -SO ₂ OR ^a , wherein R ^a and R ^b are each independently hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, COOH Substituted with one or more substituents selected from the group consisting of: -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Unsubstituted C1-C8 alkyl;
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C3-C8 cycloalkyl or C3-C8 heterocycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of groups; or
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with one or more substituents selected from the group consisting of groups;
Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;
Y is halogen, OH or aldehyde,
R1 is hydrogen, halogen, CN, NO ₂ , guanidino, straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, trihalo (C1-C4) Alkoxy, trihalo (C 1 -C 4) alkyl,-(CH ₂ ) _0-6 -R ^a , -C2-C6 alkenyl-R ^a ,-(CH ₂ ) _0-6 -OR ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) R ^a ,-(CH ₂ ) _{0 ~ 6} -C (O) OR ^a ,-(CH ₂ ) _{0 ~ 6} -S (O) R ^a ,-(CH ₂ ) _{0 6-} SO ₂ R ^a , -OC (O) R ^a , -NR ^a R ^b , -NH- (CH ₂ ) _0-6 -R ^a , -NHC (O) R ^a , -C (O) NR ^a R ^b , -NHC (S) R ^a , -C (S) NR ^a R ^b , -SR ^a , -NHSO ₂ R ^a , -SO ₂ NR ^a R ^b , -OSO ₂ R ^a , or -SO ₂ OR ^a , wherein R ^a and R ^b are each independently hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, COOH Substituted with one or more substituents selected from the group consisting of: -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Unsubstituted C1-C8 alkyl;
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C3-C8 cycloalkyl or C3-C8 heterocycloalkyl unsubstituted or substituted with one or more substituents selected from the group consisting of groups; or
C1-C6 alkyl, C1-C6 alkoxy, hydroxy (C1-C5) alkyl, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1 -C4 dialkylamino, OH, COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, trihalo (C1-C4) alkyl,-(CH ₂ ) _0-6 -C (O) R ^c ,-(CH ₂ ) _0-6 -C (O) OR ^c ,-(CH ₂ ) _0-6 -C (O) -NR ^c R ^d , -CH (C1-C5 alkyl) -C (O) R ^c , -CH (C1-C5 alkyl) -C (O) OR ^c , -CH (C1-C5 alkyl) -C (O) -NR ^c R ^d ,- (CH ₂ ) _0-6 -SO ₂ R ^c ,-(CH ₂ ) _0-6 -OC (O) R ^c , -NHC (O) R ^c , -C (O)-(CH ₂ ) _1-5 -R ^c , -C (O)-(CH ₂ ) _0-5 -NR ^c R ^d , -NHC (S) R ^c , -C (S) NR ^c R ^d , -NHSO ₂ R ^c , -SO ₂ NR ^c R ^d ,

,

And

C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with one or more substituents selected from the group consisting of groups;
Wherein V is a carbon atom, a nitrogen atom, or an oxygen atom, Z is a carbon atom or a simple bond, W is a carbon atom, a nitrogen atom or an oxygen atom, and n is an integer of 0 to 5; R ^c and R ^d are each independently hydrogen, halogen, OH, amino, CN, -COOH, -CONH ₂ , BOC, C1-C5 alkoxy, amino (C1-C5) alkyl,-(C1-C5) alkylamide, C1-C5 dialkylamino (C1-C5) alkyl, substituted or unsubstituted C1-C8 alkyl, 4- (C1-C8 alkyl) -pyrerazin-1-yl, 4- (C1-C8 alkyl)- Pyrerazin-1-yl (C1-C5) alkyl, morpholino carbonyl, phenyl (C1-C5) alkyl, C3-C8 cycloalkyl (C1-C5) alkyl, C3-C8 heterocycloalkyl (C1-C5) Alkyl, carboxyl-substituted cycloalkene, C1-C8 alkyl group substituted or unsubstituted C3-C8 cycloalkyl, OH or C1-C8 alkyl group substituted or unsubstituted C3-C8 heterocycloalkyl, C1-C8 alkyl group C6 ~ C18 aryl unsubstituted or substituted with C6 ~ C18 aryl or C5 ~ C18 heteroaryl unsubstituted or substituted with a C1-C8 alkyl group;
R2 is hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 alkenyl, C2- C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, (C1-C4) alkyl substituted with C3-C8 heterocycloalkyl group, trihalo ( C 1 -C 4) alkoxy, trihalo (C 1 -C 4) alkyl, C 1 -C 4 dialkylamino, amines substituted by straight or branched C 1 -C 8 alkyl groups, amines substituted by C 3 -C 8 cycloalkyl groups, C 1 -C 6 Alkylamino (C1-C4) alkyl, C1-C6 dialkylamino (C1-C8) alkyl, C1-C6 alkyleneimino (C1-C4) alkyl group, or-(CH ₂ ) _0-6 -NR ^a , Where R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C3-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH, One or more substituents selected from the group consisting of -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl A substituted or unsubstituted C6-C18 aryl or C3-C18 heteroaryl group;
R3 is hydrogen; halogen; CN; NO ₂ ; OH; -SH; -COOH; Formyl; Guanidino; -CONH ₂ ; Straight or branched C1-C8 alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C1-C8 alkoxy; Straight or branched C1-C8 alkyl containing one or more hetero atoms; -(CH ₂ ) _0-6 -R-(CH ₂ ) _0-6 -C (O) R ^a ; Or -NH (CH ₂ ) _0-6 -R ^a , wherein R ^a is hydrogen; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C1-C8 alkyl; C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, OH,- Substituted with one or more substituents selected from the group consisting of COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl Or unsubstituted C3-C8 cycloalkyl or C2-C8 heterocycloalkyl; Or C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, NO ₂ , NH ₂ , guanidino, C1-C4 alkylamino, C1-C4 dialkylamino, One or more selected from the group consisting of OH, -COOH, -COO (C1-C4 alkyl), -CONH ₂ , formyl, oxo, trihalo (C1-C4) alkoxy, and trihalo (C1-C4) alkyl groups C 6 -C 18 aryl or C 3 -C 18 heteroaryl group unsubstituted or substituted with a substituent;
R4 and R5 are each independently hydrogen, halogen, CN, NO ₂ , NH ₂ , OH, -SH, -COOH, formyl, guanidino, -CONH ₂ , straight or branched C1-C8 alkyl, C2-C8 Alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C3-C8 cycloalkyl, (C1-C4) alkyl substituted with C3-C8 cycloalkyl group, trihalo (C1-C4) alkoxy, trihalo (C1 -C4) alkyl, amine substituted with straight or branched C1-C8 alkyl group, or amine substituted with C3-C8 cycloalkyl group;
In the above, the alkyl group means a branched or branched alkyl group, and each R ^C may be independently selected when there are a plurality of R ^Cs in a molecule. The method of claim 7, wherein the compound of Formula 3 is obtained by reacting a compound of Formula 6 with a compound of Formula 7 under a base:
[Formula 6]

[Formula 7]

In Chemical Formulas 6 and 7,
The definitions of D, X, Y, R2, R4, and R5 are the same as those of Chemical Formula 3 of Claim 7. The method of claim 7, wherein the compound of Formula 3 is obtained by reacting a compound of Formula 8 or a compound of Formula 9 with a compound of Formula 10 under a base:
[Chemical Formula 8]

[Formula 9]

[Formula 10]

In Chemical Formulas 8 to 10,
The definitions of D, X, Y, R2, R4, and R5 are the same as those of Chemical Formula 3 of Claim 7.