KR20070012477A - Pyrimidine derivatives for the treatment of abnormal cell growth - Google Patents

Pyrimidine derivatives for the treatment of abnormal cell growth Download PDF

Info

Publication number
KR20070012477A
KR20070012477A KR1020067023767A KR20067023767A KR20070012477A KR 20070012477 A KR20070012477 A KR 20070012477A KR 1020067023767 A KR1020067023767 A KR 1020067023767A KR 20067023767 A KR20067023767 A KR 20067023767A KR 20070012477 A KR20070012477 A KR 20070012477A
Authority
KR
South Korea
Prior art keywords
ylamino
methyl
alkyl
trifluoromethyl
dihydro
Prior art date
Application number
KR1020067023767A
Other languages
Korean (ko)
Other versions
KR100886990B1 (en
Inventor
마이클 조셉 루치오
존 찰스 케이트
Original Assignee
화이자 프로덕츠 인크.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34966230&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=KR20070012477(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by 화이자 프로덕츠 인크. filed Critical 화이자 프로덕츠 인크.
Publication of KR20070012477A publication Critical patent/KR20070012477A/en
Application granted granted Critical
Publication of KR100886990B1 publication Critical patent/KR100886990B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Abstract

The present invention relates to a compound of the formula (I) wherein R1-R4 are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds. ® KIPO & WIPO 2007

Description

비정상적인 세포성장의 치료를 위한 피리미딘 유도체{PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH}Pyrimidine derivatives for the treatment of abnormal cell growth {PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH}

관련 출원에 대한 상호-참조Cross-Reference to the Related Application

2002년 12월 20일자 출원된 미국 특허출원 제 60/435,670 호 (Attorney Docket No. PC25339) 및 2003년 9월 5일자 출원된 미국 특허출원 제 60/500,742 호 (Attorney Docket No. PC25937)를 참고로 한다.See US Patent Application No. 60 / 435,670 filed December 20, 2002 (Attorney Docket No. PC25339) and US Patent Application No. 60 / 500,742 filed September 5, 2003 (Attorney Docket No. PC25937). do.

발명의 배경Background of the Invention

본 발명은 포유동물에서 암과 같은 비정상적인 세포성장의 치료에 유용한 신규의 피리미딘 유도체에 관한 것이다. 본 발명은 또한, 포유동물, 특히 인간에게서 비정상적인 세포성장의 치료 시에 이러한 화합물을 사용하는 방법, 및 이러한 화합물을 함유하는 약제학적 조성물에 관한 것이다.The present invention relates to novel pyrimidine derivatives useful for the treatment of abnormal cell growth such as cancer in mammals. The invention also relates to methods of using such compounds in the treatment of abnormal cell growth in mammals, in particular humans, and pharmaceutical compositions containing such compounds.

세포는 그의 DNA의 일부분을 종양원 (즉, 활성화하면 악성 종양세포의 형성을 유도하는 유전자)으로 형질전환시킴으로써 암성이 될 수 있는 것으로 알려져 있다. 다수의 종양원은 세포 형질전환을 야기할 수 있는 비정상 타이로신 키나제인 단백질을 코딩한다. 또는, 정상적인 원종양원성 타이로신 키나제의 과발현이 또한 증식성 질환을 야기할 수 있으며, 때때로 악성 표현형을 나타낼 수 있다.Cells are known to be cancerous by transforming a portion of their DNA with a tumor source (ie, a gene that, upon activation, leads to the formation of malignant tumor cells). Many tumor sources encode proteins that are abnormal tyrosine kinases that can cause cellular transformation. Alternatively, overexpression of normal prototypical tyrosine kinases can also lead to proliferative diseases and sometimes exhibit a malignant phenotype.

수용체 타이로신 키나제는 세포막에 걸려있으며, 표피성장인자와 같은 성장인자에 대한 세포와 결합영역, 막횡단 영역, 및 단백질 내의 특정 타이로신 잔기를 포스포릴화시킴으로써 세포 증식에 영향을 미치는 키나제로서 작용하는 세포내 부분을 포함하는 효소이다. 그 밖의 다른 수용체 타이로신 키나제에는 c-erB-2, c-met, tie-2, PDGFr, FGFr 및 VEGFR이 포함된다. 이러한 키나제는 유방암, 결장암, 직장암 또는 위암과 같은 위장관암, 백혈병, 및 난소암, 기관지암 또는 췌장암과 같은 통상적인 인간 암에서 빈번하게 비정상 발현되는 것으로 알려져 있다. 또한, 타이로신 키나제 활성을 갖는 표피성장인자 수용체 (EGFR)은 뇌, 폐, 편평세포, 방광, 위, 유방, 두경부, 식도, 부인과적 및 갑상선 종양과 같은 다수의 인간 암에서 돌연변이되고/되거나 과발현되는 것으로 알려져 있다.Receptor tyrosine kinases hang on the cell membrane and act as kinases that affect cell proliferation by phosphorylating specific tyrosine residues in cells and binding regions, transmembrane regions, and proteins for growth factors such as epidermal growth factor. It is an enzyme that contains a moiety. Other receptor tyrosine kinases include c-erB-2, c-met, tie-2, PDGFr, FGFr and VEGFR. Such kinases are known to be frequently abnormally expressed in gastrointestinal cancers such as breast cancer, colon cancer, rectal cancer or gastric cancer, leukemia, and common human cancers such as ovarian cancer, bronchial cancer or pancreatic cancer. In addition, epidermal growth factor receptor (EGFR) with tyrosine kinase activity is mutated and / or overexpressed in many human cancers such as brain, lung, squamous cell, bladder, stomach, breast, head and neck, esophagus, gynecological and thyroid tumors. It is known.

따라서, 수용체 타이로신 키나제의 억제제는 포유동물 암세포의 성장의 선택적 억제제로서 유용한 것으로 인식되고 있다. 예를 들어, 타이로신 키나제 억제제인 에르브스타틴 (erbstatin)은 무흉선성 누드 마우스 (athymic nude mice)에서 표피성장인자 수용체 타이로신 키나제 (EGFR)을 발현하는 이식된 인간 유방암의 성장을 선택적으로 약화시키지만, EGF 수용체를 발현하지 않는 다른 암의 성장에 대해서는 영향을 미치지 않는다. 따라서, 특정의 수용체 타이로신 키나제의 선택적 억제제는 포유동물에서 비정상적인 세포성장, 특히 암의 치료에 유용하다. 수용체 타이로신 키나제 이외에도, FAK (focal adhesion kinase), lck, src, abl 또는 세린/트레오닌 키나제 (예를 들어, 사이클린 의존성 키나제)와 같은 특정의 비-수용체 타이로신 키나제의 선택적 억제제가 포유동물에서 비정상적인 세포성장, 특히 암의 치료에 유용하다. FAK는 또한 단백질-타이로신 키나제 2, PTK2로 공지되어 있다.Thus, inhibitors of receptor tyrosine kinases are recognized as useful as selective inhibitors of the growth of mammalian cancer cells. For example, the tyrosine kinase inhibitor erbstatin selectively attenuates the growth of transplanted human breast cancers expressing epidermal growth factor receptor tyrosine kinase (EGFR) in athymic nude mice, It does not affect the growth of other cancers that do not express EGF receptors. Thus, selective inhibitors of certain receptor tyrosine kinases are useful in the treatment of abnormal cell growth, particularly cancer, in mammals. In addition to receptor tyrosine kinases, selective inhibitors of certain non-receptor tyrosine kinases, such as focal adhesion kinase (FAK), lck, src, abl or serine / threonine kinases (eg, cyclin dependent kinases), cause abnormal cell growth in mammals. , Especially useful in the treatment of cancer. FAK is also known as protein-tyrosine kinase 2, PTK2.

설득력있는 증거는 세포질 비-수용체 타이로신 키나제인 FAK가 세포-매트릭스 단일 형질도입 경로에서 필수적인 역할을 하며 (Clark and Brugge 1995, Science 268: 233-239), 그의 비정상 활성화는 종양의 전이 잠재성의 증거와 연관이 있음 (Owens et al. 1995, Cancer Research 55: 2752-2755)을 시사한다. FAK는 최초에 v-Src에 의해서 형질전환된 세포에서 고도로 타이로신-포스포릴화된 125 kDa 단백질로 확인되었다. 그 후, FAK는 배양된 세포와 그들의 원기질 및 강력한 타이로신 포스포릴화의 잔기 사이의 접촉점인 병소 유착부에 국재화하는 타이로신 키나제인 것으로 밝혀졌다. FAK는 인테그린에 대한 세포와 매트릭스 (ECM)-결합에 대한 반응으로 포스포릴화되고, 따라서 활성화된다. 최근에, 연구에 의해서 종양의 침습성 형질전환 및 FAK의 발현의 감쇠 (안티센스 올리고뉴클레오타이드의 사용으로 인함)를 수반하는 FAK mRNA 레벨의 증가가 종양세포의 세포소멸을 유도하는 것으로 입증되었다 (Xu et al. 1996, Cell Growth and Diff . 7: 413-418). FAK는 대부분의 조직 타입에서 발현될 뿐만 아니라, 대부분의 인간 암, 특히 매우 침습성인 전이부에서 상승된 레벨로 확인된다.Convincing evidence suggests that FAK, a cytoplasmic non-receptor tyrosine kinase, plays an essential role in the cell-matrix single transduction pathway (Clark and Brugge 1995, Science 268 : 233-239), and its abnormal activation is evidence of tumor metastasis potential. Related (Owens et al. 1995, Cancer Research 55 : 2752-2755). FAK was initially identified as a highly tyrosine-phosphorylated 125 kDa protein in cells transformed with v-Src. FAK was then found to be tyrosine kinases localizing to focal adhesions, which are the contact points between cultured cells and their primitive and residues of potent tyrosine phosphorylation. FAK is phosphorylated in response to matrix (ECM) -binding with cells for integrin and is thus activated. Recently, studies have demonstrated that an increase in FAK mRNA levels accompanied by invasive transformation of tumors and attenuation of FAK expression (due to the use of antisense oligonucleotides) induces apoptosis of tumor cells (Xu et al. 1996, Cell Growth and Diff . 7 : 413-418). FAK is not only expressed in most tissue types, but is also identified at elevated levels in most human cancers, especially in highly invasive metastases.

스티렌 유도체와 같은 다양한 화합물은 또한, 타이로신 키나제 억제특성을 갖는 것으로 나타났다. 5개의 유럽특허공보, 즉 EP 0 566 226 A1 (1993년 10월 20일에 공개됨), EP 0 602 851 A1 (1994년 6월 22일에 공개됨), EP 0 635 507 A1 (1995년 1월 25일에 공개됨), EP 0 635 498 A1 (1995년 1월 25일에 공개됨), 및 EP 0 520 722 A1 (1992년 12월 30일에 공개됨)은 그들의 타이로신 키나제 억제특성으로 인한 항암특성을 갖는 것으로 특정의 비사이클릭 유도체, 특히 퀴나졸린 유도체를 언급하고 있다.Various compounds, such as styrene derivatives, have also been shown to have tyrosine kinase inhibitory properties. Five European patent publications, EP 0 566 226 A1 (published 20 October 1993), EP 0 602 851 A1 (published June 22, 1994), EP 0 635 507 A1 (January 25, 1995) Published), EP 0 635 498 A1 (published January 25, 1995), and EP 0 520 722 A1 (published December 30, 1992) have anticancer properties due to their tyrosine kinase inhibitory properties. Reference is made to certain acyclic derivatives, in particular quinazoline derivatives.

또한, 국제특허출원 WO 92/20642 (1992년 11월 26일에 공개됨)는 비정상적인 세포증식을 억제하는데 유용한 타이로신 키나제 억제제로서 특정의 비스-모노 및 비사이클릭 아릴 및 헤테로아릴 화합물을 언급하였다. 국제특허출원 WO 96/16960 (1996년 6월 6일에 공개됨), WO 96/09294 (1996년 3월 6일에 공개됨), WO 97/30034 (1997년 8월 21일에 공개됨), WO 98/02434 (1998년 1월 22일에 공개됨), WO 98/02437 (1998년 1월 22일에 공개됨), 및 WO 98/02438 (1998년 1월 22일에 공개됨)도 또한 동일한 목적에 유용한 타이로신 키나제 억제제로서 치환된 비사이클릭 헤테로방향족 유도체를 언급하였다. 또한, 이하의 공보 리스트는 임의로 타이로신 키나제 억제제로서 사용될 수 있는 비스-모노 및 비사이클릭 아릴 및 헤테로아릴 화합물에 관한 것이다: WO 03/030909, WO 03/032997, 미국특허출원 제 2003/0181474 호, 미국특허출원 제 2003/0162802 호, 미국특허 제 5,863,924 호, WO 03/078404, 미국특허 제 4,507,146 호, WO 99/41253, WO 01/72744, WO 02/48133, 미국특허출원 제 2002/156087 호, WO 02/102783, 및 WO 03/063794.In addition, international patent application WO 92/20642 (published November 26, 1992) refers to certain bis-mono and bicyclic aryl and heteroaryl compounds as tyrosine kinase inhibitors useful for inhibiting abnormal cell proliferation. International Patent Application WO 96/16960 (published 6 June 1996), WO 96/09294 (published March 6, 1996), WO 97/30034 (published August 21, 1997), WO 98 / 02434 (published January 22, 1998), WO 98/02437 (published January 22, 1998), and WO 98/02438 (published January 22, 1998) are also useful tyrosine for the same purpose. Mention is made of substituted bicyclic heteroaromatic derivatives as kinase inhibitors. The following publication list also relates to bis-mono and bicyclic aryl and heteroaryl compounds which may optionally be used as tyrosine kinase inhibitors: WO 03/030909, WO 03/032997, US Patent Application 2003/0181474, U.S. Patent Application 2003/0162802, U.S. Patent 5,863,924, WO 03/078404, U.S. Patent 4,507,146, WO 99/41253, WO 01/72744, WO 02/48133, U.S. Patent Application 2002/156087, WO 02/102783, and WO 03/063794.

2003년 12월 11일에 출원된 미국특허출원 제 10/734,039 호 (Attorney Docket No. PC25339A)는 키나제 억제제, 더욱 특히는 FAK의 억제제인 광범위한 부류의 신규한 피리미딘 유도체에 관한 것이다. 더욱이, 2003년 12월 11일에 출원된 미국특허출원 제 10/733,215 호 (Attorney Docket No. PC25937A)는 더욱 구체적으 로 타이로신 키나제 억제제, 더욱 특히는 FAK 억제제인 피리미딘 유도체의 하위 집합 즉 5-아미노옥스인돌을 갖는 화합물에 관한 것이다. 이들과 같은 화합물은 비정상적인 세포성장의 치료에 유용하다.US Patent Application No. 10 / 734,039 filed December 11, 2003 (Attorney Docket No. PC25339A) relates to a broad class of novel pyrimidine derivatives that are kinase inhibitors, more particularly inhibitors of FAK. Moreover, US Patent Application No. 10 / 733,215, filed Dec. 11, 2003 (Attorney Docket No. PC25937A), is more specifically a subset of pyrimidine derivatives that are tyrosine kinase inhibitors, more particularly FAK inhibitors, namely 5- The present invention relates to a compound having aminooxindole. Compounds such as these are useful for the treatment of abnormal cell growth.

따라서, 포유동물에서 암과 같은 비정상적인 세포성장의 치료에 유용한 특정의 수용체 및 비-수용체 타이로신 키나제의 추가의 선택적 억제제에 대한 필요성이 존재한다. 본 발명은 키나제 억제제 및 비-수용체 타이로신 키나제인 FAK의 억제제이며, 비정상적인 세포성장의 치료에 유용한 신규한 피리미딘 유도체를 제공한다.Thus, there is a need for additional selective inhibitors of certain receptors and non-receptor tyrosine kinases useful in the treatment of abnormal cell growth such as cancer in mammals. The present invention provides novel pyrimidine derivatives that are inhibitors of FAK, a kinase inhibitor and a non-receptor tyrosine kinase, and are useful in the treatment of abnormal cell growth.

발명의 요약Summary of the Invention

따라서, 본 발명은 하기 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물, 수화물 또는 프로드럭 (prodrug)을 제공한다:Accordingly, the present invention provides a compound of Formula 1, or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof:

Figure 112006082893189-PCT00001
Figure 112006082893189-PCT00001

상기 식에서,Where

n은 1 내지 3의 정수이며;n is an integer from 1 to 3;

각각의 R1은 수소, 하이드록시, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2- C9)헤테로사이클릴, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -NR5R6, -SR7, -SOR7, -SO2R7, -CO2R12, -CONR5R6, -SO2NR5R6, -NHCOR12, -NR12CONR5R6, 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택되는 치환체이고, 여기에서 상기 R1 치환체인 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -NR5R6, -SR7, -SOR7, -SO2R7, -CO2R12, -CONR5R6, -SO2NR5R6, -NHCOR12, -NR12CONR5R6, 및 -NR12SO2R7은 수소, 할로겐, 하이드록시, -CF3, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며;Each R 1 is hydrogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -O (C 1 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -NR 5 R 6 , -SR 7 , -SOR 7 , -SO 2 R 7 ,- A substituent independently selected from the group consisting of CO 2 R 12 , -CONR 5 R 6 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 , and -NR 12 SO 2 R 7 , Wherein the R 1 substituent is-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -O (C 1 -C 6 ) alkyl , -O (C 3 -C 7 ) cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -NR 5 R 6 , -SR 7 , -SOR 7 , -SO 2 R 7 , -CO 2 R 12 , -CONR 5 R 6 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 , and -NR 12 SO 2 R 7 are hydrogen, halogen, hydroxy, -CF 3 , -CN ,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , Consisting of -CONR 5 R 6 and -CONR 5 R 8 Optionally substituted by one to three residues independently selected from the group;

각각의 R2는 수소, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12 및 -CONR5R6로 구성된 군으로부터 독립적으로 선택되는 치환체이고, 여기에서 상기 R2 치환체인 -(C1-C6)알킬, -(C2-C6)알 케닐, -(C2-C6)알키닐, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12 및 -CONR5R6은 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있거나;Each R 2 is hydrogen,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 and -CONR 5 R 6 is a substituent independently selected from the group consisting of the R 2 substituents-(C 1 -C 6 ) alkyl ,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 and -CONR 5 R 6 are hydrogen, halogen, hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl ,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 Optionally substituted by one to three residues independently selected from the group consisting of R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6, and -NR 12 SO 2 R 7 , wherein said-(C 2 -C 6 )egg Carbonyl, and - (C 2 -C 6) alkynyl R 2 moieties may be optionally substituted by one to three groups R 12;

R1 및 R2는 이들이 부착된 원자(들)과 함께 사이클릭 기, -(C3-C10)사이클로알킬 또는 -(C2-C9)헤테로사이클릴을 형성할 수 있고, 여기에서 상기 사이클릭 기는 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 상기 사이클릭 기의 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고, 상기의 사이클릭 기는 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재되며;R 1 and R 2 together with the atom (s) to which they are attached may form a cyclic group, — (C 3 -C 10 ) cycloalkyl or — (C 2 -C 9 ) heterocyclyl, wherein Cyclic groups are hydrogen, halogen, hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 is optionally substituted with 1 to 3 residues independently selected from the above-(C 2 -C 6 of the cyclic group ) Alkenyl and-(C 2 -C 6 ) alkynyl moieties may be optionally substituted by one to three R 12 groups, wherein the cyclic groups are-(C═O), —SO 2 , —S—, A line from the group consisting of -O-, -N-, -NH-, and -NR 12 Optionally one to three selected elements are interposed;

R3는 (a) 수소; R 3 is (a) hydrogen;

(b) 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1- C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C6-C10)아릴 또는 -(C1-C9)헤테로아릴 (여기에서, 상기의 -(C6-C10)아릴 또는 -(C1-C9)헤테로아릴은 -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다); (b) halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl) 2 ,-(C 3- C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 1- C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ( (C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl,- O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3 -C 10 ) cycloalkyl,-( CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl,- (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) alkyl, -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3 , -SO 2 NH 2 , -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1 -C 6 ) alkyl) ((C 3 -C 6 ) cyclo -(C 6 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 10 ) aryl or-(C 1 -C 9 ) heteroaryl (wherein-(C 6 -C 10 ) aryl or-(C 1 -C 9 ) heteroaryl is -S-, -O-,- Optionally interrupted by 1 to 3 elements selected from the group consisting of N—, —NH— and —NR 12 );

(c) 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1-C6)알킬-(C2-C9)헤테로사이클릴 (여기에서, 상기의 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1-C6)알킬-(C2-C9)헤테로사이클릴은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다); 및 (c) halogen, hydroxy, - (C 1 -C 6) alkyl, - (C 1 -C 6) alkyl, -P (O) (O (C 1 -C 6) alkyl) 2, - (C 3 - C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 1- C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ( (C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl,- O-SO 2 (C 1 -C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-( CO) (C 3 -C 10 ) cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl, - (CO) O (C 1 -C 6) alkyl, - (CO) O (C 3 -C 10) cycloalkyl, - (CO) O (C 6 -C 10) aryl, - (CO ) O (C 2 -C 9 ) heterocyclyl,-(CO) O (C 1 -C 9 ) heteroaryl,-(CO) (C 1 -C 6 ) alkyl -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3, -SO 2 NH 2, -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1- C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 are independently selected from the group consisting of -(C 3 -C 10 ) cycloalkyl, optionally substituted by three residues,-(C 2 -C 9 ) heterocyclyl and-(C 1 -C 6 ) alkyl- (C 2 -C 9 ) heterocycle Reel (wherein-(C 3 -C 10 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl and-(C 1 -C 6 ) alkyl- (C 2 -C 9 ) heterocyclyl Is optionally interrupted by 1 to 3 elements selected from the group consisting of — (C═O), —SO 2 , —S—, —O—, —N—, —NH—, and —NR 12 ); And

(d) 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬 (여기에서, 상기의 -(C1-C6)알킬은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)로 구성된 군으로부터 선택된 치환체이고,(d) halogen, hydroxy, - (C 1 -C 6) alkyl, - (C 1 -C 6) alkyl, -P (O) (O (C 1 -C 6) alkyl) 2, - (C 3 - C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 1- C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ( (C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl,- O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3 -C 10 ) cycloalkyl,-( CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl,- (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) alkyl, -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3 , -SO 2 NH 2 , -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1 -C 6 ) alkyl) ((C 3 -C 6 ) cyclo -(C 1 -C 6 ) optionally substituted by 1 to 3 residues selected from the group consisting of alkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 Alkyl, wherein — (C 1 -C 6 ) alkyl is a group consisting of — (C═O), —SO 2 , —S—, —O—, —N—, —NH—, and —NR 12 1 to 3 elements selected from are optionally interposed), a substituent selected from the group consisting of

여기에서 각각의 R3 (b)-(d) 치환체, 잔기 또는 원소는 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴, -(C1-C9)헤테로아릴, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -C=N-OH, -C=N-O(C1-C6 알킬), -NR5R6, -SR7, -SOR7, -SO2R7, -CO2R12, -CONR5R6, -SO2NR5R6, -NHCOR5, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 래디칼에 의해서 임의로 치환되며;Wherein each R 3 (b)-(d) substituent, residue, or element is hydrogen, halogen, hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl, - (C 1 -C 9) heteroaryl, -O (C 1 -C 6) alkyl, -O (C 3 -C 7) cycloalkyl, -O (C 2 -C 9) heterocyclyl, - C = N-OH, -C = NO (C 1 -C 6 alkyl), -NR 5 R 6 , -SR 7 , -SOR 7 , -SO 2 R 7 , -CO 2 R 12 , -CONR 5 R 6 Is optionally substituted with 1 to 3 radicals independently selected from the group consisting of -SO 2 NR 5 R 6 , -NHCOR 5 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 ;

R4는 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택된 치환체이고, 여기에서 상기의 -(C1-C6)알킬, -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴 R4 치환체는 수소, 할로겐, 하이드록시, -(C1-C6)알킬, -CN, -NR5R6, -OR5, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -SO2NR5R6, -NR12SO2R7, -SO2R7 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 상기 -CONR5R8 기의 R5 및 R8은 이들이 부착된 원자와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있고;R 4 is a substituent selected from the group consisting of hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl, wherein C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl R 4 substituents are hydrogen, halogen, hydroxy,-(C 1 -C 6 ) alkyl , -CN, -NR 5 R 6 , -OR 5 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -SO 2 NR 5 R 6 , -NR 12 SO 2 R 7 , -SO 2 R 7 and -CONR 5 R 8 are optionally substituted with 1 to 3 residues independently selected from the group consisting of R 5 of the above-CONR 5 R 8 groups And R 8 together with the atoms to which they are attached may form — (C 2 -C 9 ) heterocyclyl;

R5 및 R6는 각각 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴, -(C1-C9)헤테로아릴, -COR12 및 -SO2R12로 구성된 군으로부터 독립적으로 선택된 치환체이며, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴, -(C1-C9)헤테로아릴, -COR12 및 -SO2R12인 R5 또는 R6 치환체는 수소, 할로겐, -CF3, -CN, -(C1-C6)알킬, -NH(C1-C6)알킬, -NH(C3-C7)사이클로알킬, -NH(C2-C9)헤테로사이클릴, -NH(C6-C10)아릴, -NH(C1-C9)헤테로아 릴, -N((C1-C6)알킬)2, -N((C3-C7)사이클로알킬)2, -N((C2-C9)헤테로사이클릴)2, -N((C6-C10)아릴)2, -N((C1-C9)헤테로아릴)2, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -O(C6-C10)아릴, -O(C1-C9)헤테로아릴, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R7, -SO2NR5R6, -NR12SO2R7, -SO2R7, -CONH2, -CONHR7 및 -CONR7R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되고, 여기에서 상기 -CONR7R8의 R7 및 R8은 이들이 부착된 질소와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있거나;R 5 and R 6 are each hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) Aryl,-(C 1 -C 9 ) heteroaryl, -COR 12 and -SO 2 R 12 is a substituent independently selected from the group consisting of-(C 1 -C 6 ) alkyl,-(C 3- C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl,-(C 1 -C 9 ) heteroaryl, -COR 12 and -SO 2 R 12 5 or R 6 substituents are hydrogen, halogen, -CF 3 , -CN,-(C 1 -C 6 ) alkyl, -NH (C 1 -C 6 ) alkyl, -NH (C 3 -C 7 ) cycloalkyl, -NH (C 2 -C 9 ) heterocyclyl, -NH (C 6 -C 10 ) aryl, -NH (C 1 -C 9 ) heteroaryl, -N ((C 1 -C 6 ) alkyl) 2 , -N ((C 3 -C 7 ) cycloalkyl) 2 , -N ((C 2 -C 9 ) heterocyclyl) 2 , -N ((C 6 -C 10 ) aryl) 2 , -N (( C 1 -C 9 ) heteroaryl) 2 , -O (C 1 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -O ( C 6 -C 10 ) aryl, -O (C 1 -C 9 ) heteroaryl,-(C 3 -C 7 ) Dichloroalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 7 , -SO 2 NR 5 R 6 , -NR 12 SO 2 R 7 , -SO 2 R 7 , -CONH 2 , -CONHR And optionally substituted with 1 to 3 residues independently selected from the group consisting of 7 and -CONR 7 R 8 , wherein R 7 and R 8 of -CONR 7 R 8 together with the nitrogen to which they are attached-(C 2 -C 9 ) may form heterocyclyl;

R5 및 R6가 이들이 부착된 원자(들)와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있으며, 여기에서 상기 -(C2-C9)헤테로사이클릴 기는 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR7R8, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR7R8, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR7R8, -NHCOR12, -NR12CONR7R8 및 -NR12SO2R7로 구성된 군으로부터 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되고, 여기에서 상기 -(C2-C9)헤테로사이클릴 기의 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R7 기에 의해서 임의로 치환되고, 상기의 -(C2-C9)헤테로사이클릴 기는 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재되며;R 5 and R 6 together with the atom (s) to which they are attached may form-(C 2 -C 9 ) heterocyclyl, wherein the-(C 2 -C 9 ) heterocyclyl group is hydrogen, halogen , Hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ( (C 1 -C 6) alkyl), -NR 7 R 8, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 -C 9) heterocyclyl Reel, -CO 2 R 12 , -CONR 7 R 8 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 7 R 8 , -NHCOR 12 , -NR 12 CONR 7 R 8, and -NR 12 SO 2 R 7 is optionally substituted by one to three moieties selected from the group consisting of, where the - (C 2 -C 9) heterocyclyl group of - (C 2 -C 6 ) Alkenyl and-(C 2 -C 6 ) alkynyl residues are optionally substituted by one to three R 7 groups, wherein the-(C 2 -C 9 ) heterocyclyl group is-(C═O),- 1 to 3 selected from the group consisting of SO 2 , -S-, -O-, -N-, -NH- and -NR 12 An element is optionally interposed;

R7은 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴로 구성된 군으로부터 선택된 치환체이고, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 R7 치환체는 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR12 2 및 -O(C1-C6)알킬로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며;R 7 is — (C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl is a substituent selected from the group consisting of wherein-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl R 7 substituents are hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 12 2 and- Optionally substituted by 1 to 3 residues independently selected from the group consisting of O (C 1 -C 6 ) alkyl;

R8은 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴로 구성된 군으로부터 선택된 치환체이고, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 R8 치환체는 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알 킬, -NH2, -NHR9, -NR9 2, -OR9, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R10, -CONH2, -CONHR10 및 -CONR10R11로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 -CONR10R11의 R10 및 R11은 이들이 부착된 질소 원자와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있고;R 8 is hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl and-( C 1 -C 9 ) heteroaryl and a substituent selected from the group consisting of wherein-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocycle Reel,-(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl R 8 substituents are hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NH 2 , -NHR 9 , -NR 9 2 , -OR 9 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 10 , -CONH 2 , -CONHR 10 and -CONR 10 R 11 and optionally by one to three moieties independently selected from the group consisting of substituted, R 10 and R 11 of -CONR 10 R 11 where, together with the nitrogen atom to which they are attached to - (C 2 - C 9 ) may form heterocyclyl;

R9 및 R10은 각각 -(C1-C6)알킬이며;R 9 and R 10 are each-(C 1 -C 6 ) alkyl;

R11은 수소 또는 -(C1-C6)알킬이고;R 11 is hydrogen or-(C 1 -C 6 ) alkyl;

R12는 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴로 구성된 군으로부터 선택된 치환체이며, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 R12 치환체는 수소, 할로겐, -CF3, -CN, -(C1-C6)알킬, -NH(C1-C6)알킬, -NH(C3-C7)사이클로알킬, -NH(C2-C9)헤테로사이클릴, -NH(C6-C10)아릴, -NH(C1-C9)헤테로아릴, -N((C1-C6)알킬)2, -N((C3-C7)사이클로알킬)2, -N((C2-C9)헤테로사이클릴)2, -N((C6-C10)아릴)2, -N((C1-C9)헤테로아릴)2, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -O(C6-C10)아릴, -O(C1-C9)헤테로아 릴, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R7, -CONH2, -CONHR7 및 -CONR7R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 -CONR7R8의 R7 및 R8은 이들이 부착된 질소 원자와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있다.R 12 is hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl and-( C 1 -C 9 ) heteroaryl, wherein the substituent is selected from the group consisting of-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocycle The aryl,-(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl R 12 substituents are hydrogen, halogen, -CF 3 , -CN,-(C 1 -C 6 ) alkyl, -NH ( C 1 -C 6 ) alkyl, -NH (C 3 -C 7 ) cycloalkyl, -NH (C 2 -C 9 ) heterocyclyl, -NH (C 6 -C 10 ) aryl, -NH (C 1- C 9 ) heteroaryl, -N ((C 1 -C 6 ) alkyl) 2 , -N ((C 3 -C 7 ) cycloalkyl) 2 , -N ((C 2 -C 9 ) heterocyclyl) 2 , -N ((C 6 -C 10 ) aryl) 2 , -N ((C 1 -C 9 ) heteroaryl) 2 , -O (C 1 -C 6 ) alkyl, -O (C 3 -C 7 ) Cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -O (C 6 -C 10 ) aryl, -O (C 1 -C 9 ) heteroaryl,-(C 3 -C 7 ) cycloalkyl ,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 7 , -CONH 2 , -CONHR 7 and -CONR 7 R 8 is optionally substituted by one to three moieties independently selected from the group consisting of, in which the -CONR 7 R 8 R 7 and R 8 are taken together with the nitrogen atom to which they are attached a - (C 2 -C 9 ) can form heterocyclyl.

본 발명은 또한, 하나 또는 그 이상의 원자가 통상적으로 자연적으로 존재하는 원자질량 또는 질량수와는 상이한 원자질량 또는 질량수를 갖는 원자로 대체된 것을 제외하면 화학식 1로 열거된 것과 동일한 동위원소-표지된 화합물도 포함한다. 본 발명의 화합물에 통합될 수 있는 동위원소의 예로는 각각 2H, 3H, 13C, 14C, 15N, 18O, 17O, 31P, 32P, 35S, 18F, 및 36Cl과 같은 수소, 탄소, 질소, 산소, 인, 불소 및 염소의 동위원소가 포함된다. 전술한 동위원소 및/또는 그 밖의 다른 원자의 동위원소를 함유하는 본 발명의 화합물, 그의 프로드럭, 및 상기 화합물 또는 프로드럭의 약제학적으로 허용되는 염은 본 발명의 범위 내에 포함된다. 본 발명의 특정한 동위원소-표지된 화합물, 예를 들어, 3H 및 14C와 같은 방사성 동위원소가 통합된 화합물은 약물 및/또는 기질 조직분포시험애서 유용하다. 삼중수소화된, 즉 3H, 및 탄소-14, 즉 14C, 동위원소가 그들의 제조 및 검출가능성의 용이성으로 인하여 특히 바람직하다. 또한, 중수소, 즉 2H와 같은 더 무거운 동위원소에 의한 치환은 더 큰 대사적 안정성, 예를 들어, 증가된 생체내 반감기 또는 감소된 투약량 필요조건으로 인하여 특정의 치료학적 이점을 제공할 수 있으며, 따라서 일부의 환경에서 바람직할 수 있다. 본 발명의 화학식 1의 동위원소-표지된 화합물 및 그의 프로드럭은 일반적으로 동위원소 표지되지 않은 시약을 용이하게 이용할 수 있는 동위원소-표지된 시약으로 치환시킴으로써 이하의 반응식 및/또는 실시예 및 제조예에 기술된 방법을 수행함으로써 제조될 수 있다.The invention also encompasses the same isotopically-labeled compounds as listed in Formula 1 except that one or more atoms are replaced by atoms having an atomic mass or mass number that is different from the atomic mass or mass number that is commonly present in nature. do. Examples of isotopes that may be incorporated into the compounds of the invention include 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 17 O, 31 P, 32 P, 35 S, 18 F, and 36, respectively. Isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine such as Cl. Compounds of the present invention, prodrugs thereof, and pharmaceutically acceptable salts of such compounds or prodrugs that contain the aforementioned isotopes and / or other isotopes of other atoms are included within the scope of the present invention. Certain isotopically-labelled compounds of the invention, such as those incorporating radioisotopes such as 3 H and 14 C, are useful in drug and / or substrate tissue distribution testing. Tritiated, ie 3 H, and carbon-14, ie 14 C, isotopes are particularly preferred due to their ease of preparation and detectability. Also, deuterium, i.e., substitution with heavier isotopes such as 2 H is greater metabolic stability, for example, due to an increased in vivo half-life or reduced dosage requirements may afford certain therapeutic advantages of and Therefore, it may be desirable in some circumstances. Isotope-labeled compounds of Formula 1 and prodrugs thereof of the present invention are generally substituted by isotopically labeled reagents with readily available isotopically-labeled reagents to provide the following schemes and / or examples and preparations. It can be prepared by carrying out the method described in the examples.

본 발명은 또한, 화학식 1의 화합물의 약제학적으로 허용되는 산부가염에 관한 것이다. 본 발명의 전술한 염기 화합물의 약제학적으로 허용되는 산부가염을 제조하기 위해서 사용되는 산은 비독성 산부가염, 즉 클로라이드, 브로마이드, 요오다이드, 니트레이트, 설페이트, 비설페이트, 포스페이트, 산 포스페이트, 아세테이트, 락테이트, 시트레이트, 산 시트레이트, 타르트레이트, 비타르트레이트, 석시네이트, 말리에이트, 푸마레이트, 글루코네이트, 사카레이트, 벤조에이트, 메탄설포네이트, 에탄설포네이트, 벤젠설포네이트, p-톨루엔설포네이트 및 파모에이트 [즉, 1,1'-메틸렌-비스-(2-하이드록시-3-나프토에이트)] 염과 같이 약물학적으로 허용되는 음이온을 함유하는 염을 형성하는 것이다.The present invention also relates to pharmaceutically acceptable acid addition salts of compounds of formula (I). Acids used to prepare pharmaceutically acceptable acid addition salts of the aforementioned base compounds of the invention are non-toxic acid addition salts, ie chlorides, bromides, iodides, nitrates, sulfates, bisulfates, phosphates, acid phosphates, acetates , Lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, saccharide, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p- To form salts containing pharmacologically acceptable anions such as toluenesulfonate and pamoate [ie, 1,1'-methylene-bis- (2-hydroxy-3-naphthoate)] salt.

본 발명은 또한, 화학식 1의 염기부가염에 관한 것이다. 사실상 산성인 이들 화학식 1의 화합물의 약제학적으로 허용되는 염기염을 제조하기 위한 시약으로 사용될 수 있는 화학적 염기는 이러한 화합물과의 비독성 염기염을 형성하는 것이다. 이러한 비독성 염기염에는 알칼리 금속 양이온 (예를 들어, 칼륨 및 나트륨) 및 알칼리 토금속 양이온 (예를 들어, 칼슘 및 마그네슘), 암모늄 또는 수용성 아 민 부가염, 예를 들어, N-메틸글루카민-(메글루민), 및 저급 알칸올암모늄 및 그 밖의 다른 약제학적으로 허용되는 유기 아민의 염기염과 같은 약물학적으로 허용되는 양이온으로부터 유도되는 것이 포함되나, 이들로 제한되지는 않는다.The invention also relates to base addition salts of formula (1). Chemical bases that can be used as reagents for preparing pharmaceutically acceptable base salts of these compounds of Formula 1 that are acidic in nature are those that form non-toxic base salts with such compounds. Such non-toxic base salts include alkali metal cations (eg potassium and sodium) and alkaline earth metal cations (eg calcium and magnesium), ammonium or water soluble amine addition salts, eg N-methylglucamine- (Meglumine), and derived from pharmacologically acceptable cations such as base salts of lower alkanolammonium and other pharmaceutically acceptable organic amines.

본 명세서에서 사용된 것으로서 문구 "약제학적으로 허용되는 염(들)"은 다른 식으로 지적되지 않는 한은, 본 발명의 화합물에 존재할 수 있는 산성 또는 염기성 기의 염을 포함한다. 사실상 염기성인 본 발명의 화합물은 다양한 무기 및 유기산에 의해서 광범위한 종류의 염을 형성할 수 있다. 이러한 염기성 화합물의 약제학적으로 허용되는 산부가염을 제조하기 위해서 사용될 수 있는 산은 비독성 산부가염, 즉 하이드로클로라이드, 하이드로브로마이드, 하이드로요오다이드, 니트레이트, 설페이트, 비설페이트, 포스페이트, 산 포스페이트, 이소니코티네이트, 아세테이트, 락테이트, 살리실레이트, 시트레이트, 산 시트레이트, 타르트레이트, 판토테네이트, 비타르트레이트, 아스코르베이트, 석시네이트, 말리에이트, 젠티시네이트, 푸마레이트, 글루코네이트, 글루쿠로네이트, 사카레이트, 포르메이트, 벤조에이트, 글루타메이트, 메탄설포네이트, 에탄설포네이트, 벤젠설포네이트, p-톨루엔설포네이트 및 파모에이트 [즉, 1,1'-메틸렌-비스-(2-하이드록시-3-나프토에이트)] 염과 같이 약물학적으로 허용되는 음이온을 함유하는 염을 형성하는 것이다. 아미노 기와 같은 염기성 잔기를 포함하는 본 발명의 화합물은 상기 언급된 산 이외에도 다양한 아미노산과의 약제학적으로 허용되는 염을 형성할 수 있다.As used herein, the phrase “pharmaceutically acceptable salt (s)” includes salts of acidic or basic groups which may be present in the compounds of the invention unless otherwise indicated. Compounds of the present invention which are essentially basic are capable of forming a wide variety of salts by various inorganic and organic acids. Acids that can be used to prepare pharmaceutically acceptable acid addition salts of these basic compounds are nontoxic acid addition salts, ie hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, iso Nicotinate, Acetate, Lactate, Salicylate, Citrate, Acid Citrate, Tartrate, Pantothenate, Bitartrate, Ascorbate, Succinate, Maleate, Genticinate, Fumarate, Gluconate , Glucuronate, saccharide, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [ie 1,1'-methylene-bis- ( 2-hydroxy-3-naphthoate)] to form salts containing pharmaceutically acceptable anions, such as salts to be. Compounds of the present invention that contain basic residues such as amino groups can form pharmaceutically acceptable salts with various amino acids in addition to the acids mentioned above.

본 발명은 또한, 화학식 1의 화합물의 프로드럭을 함유하는 약제학적 조성물을 포함한다. 유리 아미노, 아미도, 하이드록시 또는 카복실 기를 갖는 화학식 1 의 화합물은 프로드럭으로 전환될 수 있다. 프로드럭은 아미노산 잔기, 또는 두개 또는 그 이상 (예를 들어, 2, 3 또는 4개)의 아미노산 잔기의 폴리펩타이드 쇄가 펩타이드 결합을 통해서 화학식 1의 화합물의 유리 아미노, 하이드록시 또는 카복실산 기에 공유적으로 결합된 화합물을 포함한다. 아미노산 잔기는 통상적으로 3개의 문자 기호로 표시되는 20개의 천연적으로 존재하는 아미노산을 포함하며, 또한 4-하이드록시프롤린, 하이드록시리신, 데모신, 이소데모신, 3-메틸히스티딘, 노르발린, 베타-알라닌, 감마-아미노부티르산, 시트룰린, 호모시스테인, 호모세린, 오르니틴 및 메티오닌 설폰을 포함한다. 프로드럭은 또한, 카보네이트, 카바메이트, 아미드 및 알킬 에스테르가 카보닐 탄소 프로드럭 측쇄를 통해서 화학식 1의 상기 치환체에 공유적으로 결합된 화합물을 포함한다.The invention also includes pharmaceutical compositions containing prodrugs of the compound of formula (I). Compounds of formula (I) having free amino, amido, hydroxy or carboxyl groups can be converted to prodrugs. Prodrugs are those wherein the polypeptide chains of amino acid residues, or two or more (eg, 2, 3 or 4) amino acid residues are covalent to the free amino, hydroxy or carboxylic acid groups of the compound of formula 1 via peptide bonds. It includes a compound bound to. Amino acid residues comprise 20 naturally occurring amino acids, usually represented by three letter symbols, and also include 4-hydroxyproline, hydroxylysine, democin, isodemosin, 3-methylhistidine, norvaline, Beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine and methionine sulfone. Prodrugs also include compounds in which carbonates, carbamates, amides, and alkyl esters are covalently linked to the substituents of Formula 1 through carbonyl carbon prodrug side chains.

본 발명은 또한, 보호기를 함유하는 화학식 1의 화합물을 포함한다. 본 기술분야에서 숙련된 전문가는 본 발명의 화합물이 정제 또는 저장에 유용하며, 환자에게 투여하기 전에 제거될 수 있는 특정의 보호기를 사용하여 제조될 수도 있음을 인식할 수 있을 것이다. 작용기의 보호 및 탈보호는 문헌 ("Protective Groups in Organic Chemistry", edited by J.W.F. McOmie, Plenum Press (1973) 및 "Protective Groups in Organic Synthesis", 3rd edition, T.W. Greene and P.G.M. Wuts, Wiley-Interscience (1999))에 기술되어 있다.The present invention also encompasses compounds of formula 1 containing protecting groups. Those skilled in the art will appreciate that the compounds of the present invention are useful for tablets or storage and may be prepared using specific protecting groups that can be removed prior to administration to a patient. Protection and deprotection of functional groups is described in "Protective Groups in Organic Chemistry", edited by JWF McOmie, Plenum Press (1973) and "Protective Groups in Organic Synthesis", 3rd edition, TW Greene and PGM Wuts, Wiley-Interscience (1999 )).

본 발명의 화합물은 화학식 1의 화합물의 모든 입체이성체 (예를 들어, 시스 및 트랜스 이성체) 및 모든 광학이성체 (예를 들어, R 및 S 에난티오머), 및 이러한 이성체의 라세미, 부분입체이성체 및 그 밖의 혼합물을 포함한다.Compounds of the present invention include all stereoisomers (eg, cis and trans isomers) and all optical isomers (eg, R and S enantiomers) of the compounds of Formula 1, and racemic, diastereomers of such isomers. And other mixtures.

본 발명의 화합물, 염 및 프로드럭은 에놀 및 이민 형태, 및 케토 및 엔아민 형태를 포함하는 호변이성체 형태, 및 이들의 기하이성체 및 혼합물로 존재할 수 있다. 이러한 모든 호변이성체 형태는 본 발명의 범주 내에 포함된다. 호변이성체는 용액 중에서 호변이성체 셋트의 혼합물로 존재한다. 고체 형태에서는 통상적으로 하나의 호변이성체가 우세하다. 비록 하나의 호변이성체가 기술되어 있지만, 본 발명은 본 발명의 화합물의 모든 호변이성체를 포함한다.The compounds, salts and prodrugs of the present invention may exist in tautomeric forms, including enol and imine forms, and keto and enamine forms, and geometric isomers and mixtures thereof. All such tautomeric forms are included within the scope of the present invention. Tautomers exist as a mixture of tautomer sets in solution. In solid form, usually one tautomer predominates. Although one tautomer is described, the present invention includes all tautomers of the compounds of the present invention.

본 발명은 또한, 본 발명의 회전장애 이성체 (atropisomers)를 포함한다. 회전장애 이성체는 회전적으로 제한된 이성체로 분리될 수 있는 화학식 1의 화합물을 의미한다.The invention also includes atropisomers of the invention. Atropisomers refer to compounds of Formula 1 that can be separated into rotationally restricted isomers.

본 발명의 화합물은 올레핀-유사 이중결합을 함유할 수 있다. 이러한 결합이 존재하는 경우에, 본 발명의 화합물은 시스 및 트랜스 배열로, 및 이들의 혼합물로 존재한다.The compounds of the present invention may contain olefin-like double bonds. Where such bonds are present, the compounds of the present invention are present in cis and trans configurations, and in mixtures thereof.

"적합한 치환체"는 화학적으로 및 약제학적으로 허용되는 작용기, 즉 본 발명의 화합물의 생물학적 활성을 부정하지 않는 잔기를 의미하는 것이다. 이러한 적합한 치환체는 본 기술분야에서 숙련된 전문가에 의해서 일상적으로 선택될 수 있다. 적합한 치환체의 설명적 예로는 할로 기, 퍼플루오로알킬 기, 퍼플루오로알콕시 기, 알킬 기, 알케닐 기, 알키닐 기, 하이드록시 기, 옥소 기, 머캅토 기, 알킬티오 기, 알콕시 기, 아릴 또는 헤테로아릴 기, 아릴옥시 또는 헤테로아릴옥시 기, 아르알킬 또는 헤테로아르알킬 기, 아르알콕시 또는 헤테로아르알콕시 기, HO-(C=O)- 기, 아미노 기, 알킬- 및 디알킬아미노 기, 카바모일 기, 알킬카보닐 기, 알콕시카보닐 기, 알킬아미노카보닐 기, 디알킬아미노 카보닐 기, 아릴카보닐 기, 아릴옥시카보닐 기, 알킬설포닐 기, 아릴설포닐 기 등이 포함되나, 이들로 제한되지는 않는다. 본 기술분야에서 숙련된 전문가들은 다수의 치환체는 추가의 치환체에 의해서 치환될 수 있음을 알 수 있을 것이다. 적합한 치환체의 추가의 예로는 상기 정의한 바와 같은 R1 내지 R12를 포함하여 화학식 1의 화합물의 정의에서 열거된 것이 포함된다.By "suitable substituent" is meant a moiety that does not negate the chemical and pharmaceutically acceptable functional groups, ie the biological activity of the compounds of the invention. Such suitable substituents may be routinely selected by those skilled in the art. Illustrative examples of suitable substituents include halo groups, perfluoroalkyl groups, perfluoroalkoxy groups, alkyl groups, alkenyl groups, alkynyl groups, hydroxy groups, oxo groups, mercapto groups, alkylthio groups, alkoxy groups , Aryl or heteroaryl groups, aryloxy or heteroaryloxy groups, aralkyl or heteroaralkyl groups, aralkoxy or heteroaralkoxy groups, HO- (C = O)-groups, amino groups, alkyl- and dialkylamino Groups, carbamoyl groups, alkylcarbonyl groups, alkoxycarbonyl groups, alkylaminocarbonyl groups, dialkylamino carbonyl groups, arylcarbonyl groups, aryloxycarbonyl groups, alkylsulfonyl groups, arylsulfonyl groups, etc. These include, but are not limited to these. Those skilled in the art will appreciate that many substituents may be substituted by additional substituents. Further examples of suitable substituents include those listed in the definition of compounds of Formula 1, including R 1 to R 12 as defined above.

용어 "가 개재된"은 환 탄소원자가 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 원소에 의해서 치환된 화합물을 나타낸다. 예를 들어, 치환체가 화학식

Figure 112006082893189-PCT00002
와 같은 -(C6-C10)아릴인 경우에, 환은 환 탄소가 헤테로원자 질소에 의해서 치환되도록 질소 헤테로원자가 개재되거나 치환되어 화학식
Figure 112006082893189-PCT00003
의 환을 형성할 수 있다. 본 발명의 화합물은 이러한 치환부 또는 개재부를 3개까지 수용할 수 있다.The term “intervented” means that the ring carbon atom is substituted by an element selected from the group consisting of — (C═O), —SO 2 , —S—, —O—, —N—, —NH—, and —NR 12 . Represents a compound. For example, a substituent may be
Figure 112006082893189-PCT00002
In the case of-(C 6 -C 10 ) aryl, such as, the ring is substituted or substituted with a nitrogen heteroatom such that the ring carbon is substituted by a heteroatom nitrogen.
Figure 112006082893189-PCT00003
Can form a ring. The compound of the present invention can accommodate up to three such substitutions or inclusions.

본 명세서에서 사용된 것으로, 용어 "알킬", 및 본 명세서에 언급된 다른 기 (예를 들어, 알콕시)의 알킬 잔기는 선형이거나 분지될 수 있고 (예를 들어, 메틸, 에틸, n-프로필, 이소프로필, n-부틸, 이소부틸, 이급-부틸, tert-부틸); 플루오로, 클로로, 트리플루오로메틸, (C1-C6)알콕시, (C6-C10)아릴옥시, 트리플루오로메톡 시, 디플루오로메톡시 또는 (C1-C6)알킬와 같이 상기 정의한 바와 같은 1 내지 3개의 적합한 치환체에 의해서 임의로 치환될 수 있다. 본 명세서에서 사용된 것으로 문구 "각각의 상기 알킬"은 알콕시, 알케닐 또는 알키닐아미노와 같은 기 내의 어떤 선행하는 알킬 잔기라도 나타내는 것이다. 바람직한 알킬은 (C1-C6)알킬을 포함하며, 더욱 바람직한 것은 (C1-C4)알킬이고, 가장 바람직한 것은 메틸 및 에틸이다.As used herein, the alkyl moiety of the term “alkyl” and other groups (eg alkoxy) referred to herein may be linear or branched (eg, methyl, ethyl, n-propyl, Isopropyl, n-butyl, isobutyl, secondary-butyl, tert-butyl); Such as fluoro, chloro, trifluoromethyl, (C 1 -C 6 ) alkoxy, (C 6 -C 10 ) aryloxy, trifluoromethoxy, difluoromethoxy or (C 1 -C 6 ) alkyl Optionally substituted by one to three suitable substituents as defined. As used herein, the phrase "each said alkyl" refers to any preceding alkyl moiety in a group such as alkoxy, alkenyl or alkynylamino. Preferred alkyls include (C 1 -C 6 ) alkyl, more preferred are (C 1 -C 4 ) alkyl, most preferred are methyl and ethyl.

본 명세서에서 사용된 것으로, 용어 "사이클로알킬"은 1 또는 2개의 이중결합을 임의로 함유하고, 플루오로, 클로로, 트리플루오로메틸, (C1-C6)알콕시, (C6-C10)아릴옥시, 트리플루오로메톡시, 디플루오로메톡시 또는 (C1-C6)알킬과 같이 상기 정의한 바와 같은 1 내지 3개의 적합한 치환체에 의해서 임의로 치환되는 모노, 비사이클릭 또는 트리사이클릭 카보사이클 환 (예를 들어, 사이클로프로필, 사이클로부틸, 사이클로펜틸, 사이클로헥실, 사이클로헵틸, 사이클로옥틸, 사이클로노닐, 사이클로펜틸, 사이클로헥세닐, 비사이클로[2.2.1]헵타닐, 비사이클로[3.2.1]옥타닐, 및 비사이클로[5.2.0]노나닐 등)을 나타낸다.As used herein, the term “cycloalkyl” optionally contains one or two double bonds, and includes fluoro, chloro, trifluoromethyl, (C 1 -C 6 ) alkoxy, (C 6 -C 10 ) Mono, bicyclic or tricyclic carbocycle rings optionally substituted by one to three suitable substituents as defined above such as aryloxy, trifluoromethoxy, difluoromethoxy or (C 1 -C 6 ) alkyl (E.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclopentyl, cyclohexenyl, bicyclo [2.2.1] heptanyl, bicyclo [3.2.1] Octanyl, bicyclo [5.2.0] nonanyl, and the like).

본 명세서에서 사용된 것으로서, 용어 "할로겐"은 플루오로, 클로로, 브로모 또는 요오도, 또는 플루오라이드, 클로라이드, 브로마이드 또는 요오다이드를 포함한다.As used herein, the term "halogen" includes fluoro, chloro, bromo or iodo, or fluoride, chloride, bromide or iodide.

본 명세서에서 사용된 것으로서, 용어 "알케닐"은 플루오로, 클로로, 트리플루오로메틸, (C1-C6)알콕시, (C6-C10)아릴옥시, 트리플루오로메톡시, 디플루오로메톡 시 또는 (C1-C6)알킬과 같은 상기 정의한 1 내지 3개의 적합한 치환체에 의해서 임의로 치환된, 에테닐, 1-프로페닐 (알릴), 이소-프로페닐, 2-메틸-1-프로페닐, 1-부테닐, 2-부테닐 등을 포함하는 (단, 이들로 제한되지는 않는다) 탄소수 2 내지 6의 직쇄 또는 측쇄 불포화 래디칼을 의미한다.As used herein, the term "alkenyl" refers to fluoro, chloro, trifluoromethyl, (C 1 -C 6 ) alkoxy, (C 6 -C 10 ) aryloxy, trifluoromethoxy, difluorometh Messenger state or (C 1 -C 6) by 1 to 3 suitable substituents as defined above such as an optionally substituted alkyl, ethenyl, 1-propenyl (allyl), iso-propenyl, 2-methyl-1-propenyl By linear or branched unsaturated radicals having 2 to 6 carbon atoms, including but not limited to phenyl, 1-butenyl, 2-butenyl and the like.

본 명세서에서 사용된 것으로서, 용어 "알키닐"은 플루오로, 클로로, 트리플루오로메틸, (C1-C6)알콕시, (C6-C10)아릴옥시, 트리플루오로메톡시, 디플루오로메톡시 또는 (C1-C6)알킬과 같은 상기 정의한 1 내지 3개의 적합한 치환체에 의해서 임의로 치환된, 에티닐, 프로피닐, 부티닐 등을 포함하는 (단, 이들로 제한되지는 않는다) 1개의 삼중결합을 갖는 직쇄 또는 측쇄 탄화수소쇄 래디칼을 의미하는 것으로 사용된다.As used herein, the term "alkynyl" refers to fluoro, chloro, trifluoromethyl, (C 1 -C 6 ) alkoxy, (C 6 -C 10 ) aryloxy, trifluoromethoxy, difluorometh One including, but not limited to, ethynyl, propynyl, butynyl, and the like, optionally substituted with one to three suitable substituents as defined above, such as oxy or (C 1 -C 6 ) alkyl Used to mean straight or branched chain hydrocarbon radicals having triple bonds.

본 명세서에서 사용된 것으로서, 용어 "카보닐" 또는 "(C=O)" (알킬카보닐, 알킬-(C=O)- 또는 알콕시카보닐과 같은 문구에서 사용됨)는 >C=O 잔기와 알킬 또는 아미노 기 (즉, 아미도 기)와 같은 이차 잔기의 결합을 의미한다. 알콕시카보닐아미노 (즉, 알콕시(C=O)-NH-)는 알킬 카바메이트 기를 의미한다. 카보닐 기는 또한 본 명세서에서 (C=O)와 동등하게 정의된다. 알킬카보닐아미노는 아세트아미드와 같은 기를 의미한다.As used herein, the term "carbonyl" or "(C = O)" (used in phrases such as alkylcarbonyl, alkyl- (C = O)-or alkoxycarbonyl) refers to> C = O residues. By secondary bonds, such as alkyl or amino groups (ie amido groups) are meant. Alkoxycarbonylamino (ie alkoxy (C═O) —NH—) means an alkyl carbamate group. Carbonyl groups are also defined equivalently to (C═O) herein. Alkylcarbonylamino means a group such as acetamide.

본 명세서에서 사용된 것으로서, 용어 "아릴"은 상기 정의한 바와 같은 1 내지 3개의 적합한 치환체에 의해서 임의로 치환된 페닐, 나프틸, 테트라하이드로나프틸, 인다닐 등과 같은 방향족 래디칼을 의미한다.As used herein, the term "aryl" refers to aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indanyl, and the like, optionally substituted by one to three suitable substituents as defined above.

본 명세서에서 사용된 것으로서, 용어 "헤테로아릴"은 통상적으로 환 내에 O, S 및 N으로부터 선택된 하나의 헤테로원자를 갖는 방향족 헤테로사이클릭 기를 나타낸다. 상기의 헤테로원자 이외에도, 방향족 기는 임의로 환 내에 4개까지의 N 원자를 가질 수 있다. 예를 들어, 헤테로아릴 기는 플루오로, 클로로, 트리플루오로메틸, (C1-C6)알콕시, (C6-C10)아릴옥시, 트리플루오로메톡시, 디플루오로메톡시 또는 (C1-C6)알킬과 같은 상기 정의한 1 내지 3개의 적합한 치환체에 의해서 임의로 치환된 피리딜, 피라지닐, 피리미디닐, 피리다지닐, 티에닐, 푸릴, 이미다졸릴, 피롤릴, 옥사졸릴 (예를 들어, 1,3-옥사졸릴, 1,2-옥사졸릴), 티아졸릴 (예를 들어, 1,2-티아졸릴, 1,3-티아졸릴), 피라졸릴, 테트라졸릴, 트리아졸릴 (예를 들어, 1,2,3-트리아졸릴, 1,2,4-트리아졸릴), 옥사디아졸릴 (예를 들어, 1,2,3-옥사디아졸릴), 티아디아졸릴 (예를 들어, 1,3,4-티아디아졸릴), 퀴놀릴, 이소퀴놀릴, 벤조티에닐, 벤조푸릴, 인돌릴 등을 포함한다.As used herein, the term “heteroaryl” typically refers to an aromatic heterocyclic group having one heteroatom selected from O, S and N in the ring. In addition to the above heteroatoms, the aromatic group may optionally have up to four N atoms in the ring. For example, the heteroaryl group is fluoro, chloro, trifluoromethyl, (C 1 -C 6 ) alkoxy, (C 6 -C 10 ) aryloxy, trifluoromethoxy, difluoromethoxy or (C 1- C 6 ) pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thienyl, furyl, imidazolyl, pyrrolyl, oxazolyl optionally substituted by one to three suitable substituents as defined above For example, 1,3-oxazolyl, 1,2-oxazolyl), thiazolyl (eg, 1,2-thiazolyl, 1,3-thiazolyl), pyrazolyl, tetrazolyl, triazolyl (eg For example, 1,2,3-triazolyl, 1,2,4-triazolyl), oxdiazolyl (eg, 1,2,3-oxadiazolyl), thiadiazolyl (eg, 1, 3,4-thiadiazolyl), quinolyl, isoquinolyl, benzothienyl, benzofuryl, indolyl and the like.

본 명세서에서 사용된 것으로서 용어 "헤테로사이클릭"은 1-9개의 탄소원자 및 N, O, S(O)n 또는 NR로부터 선택된 1 내지 4개의 헤테로 원자를 함유하는 사이클릭 기를 나타낸다. 이러한 환의 예로는 아제티디닐, 테트라하이드로푸라닐, 이미다졸리디닐, 피롤리디닐, 피페리디닐, 피페라지닐, 옥사졸리디닐, 티아졸리디닐, 피라졸리디닐, 티오모르폴리닐, 테트라하이드로티아지닐, 테트라하이드로티아디아지닐, 모르폴리닐, 옥세타닐, 테트라하이드로디아지닐, 옥사지닐, 옥사티아지닐, 인돌리닐, 이소인돌리닐, 퀴누클리디닐, 크로마닐, 이소크로마닐, 벤즈옥사지닐 등 이 포함된다. 상기의 포화 또는 부분적으로 포화된 모노사이클릭 환 시스템의 예는 임의로 1 또는 2개의 이중결합을 함유하며, 임의로 플루오로, 클로로, 트리플루오로메틸, (C1-C6)알콕시, (C6-C10)아릴옥시, 트리플루오로메톡시, 디플루오로메톡시 또는 (C1-C6)알킬과 같은 상기 정의한 1 내지 3개의 적합한 치환체에 의해서 치환된 테트라하이드로푸란-2-일, 테트라하이드로푸란-3-일, 이미다졸리딘-1-일, 이미다졸리딘-2-일, 이미다졸리딘-4-일, 피롤리딘-1-일, 피롤리딘-2-일, 피롤리딘-3-일, 피페리딘-1-일, 피페리딘-2-일, 피페리딘-3-일, 피페라진-1-일, 피페라진-2-일, 피페라진-3-일, 1,3-옥사졸리딘-3-일, 이소티아졸리딘, 1,3-티아졸리딘-3-일, 1,2-피라졸리딘-2-일, 1,3-피라졸리딘-1-일, 티오모르폴리닐, 1,2-테트라하이드로티아진-2-일, 1,3-테트라하이드로티아진-3-일, 테트라하이드로티아디아지닐, 모르폴리닐, 1,2-테트라하이드로디아진-2-일, 1,3-테트라하이드로디아진-1-일, 1,4-옥사진-2-일, 1,2,5-옥사티아진-4-일 등이다.As used herein, the term “heterocyclic” refers to a cyclic group containing 1-9 carbon atoms and 1-4 hetero atoms selected from N, O, S (O) n or NR. Examples of such rings are azetidinyl, tetrahydrofuranyl, imidazolidinyl, pyrrolidinyl, piperidinyl, piperazinyl, oxazolidinyl, thiazolidinyl, pyrazolidinyl, thiomorpholinyl, tetrahydrothia Genyl, tetrahydrothiadiazinyl, morpholinyl, oxetanyl, tetrahydrodiazinyl, oxazinyl, oxthiazinyl, indolinyl, isoindolinyl, quinuclidinyl, chromatin, isochromenyl, benzoxazinyl And the like. Examples of such saturated or partially saturated monocyclic ring systems optionally contain 1 or 2 double bonds, optionally fluoro, chloro, trifluoromethyl, (C 1 -C 6 ) alkoxy, (C 6 Tetrahydrofuran-2-yl, tetrahydrofuran substituted by one to three suitable substituents as defined above, such as -C 10 ) aryloxy, trifluoromethoxy, difluoromethoxy or (C 1 -C 6 ) alkyl -3-yl, imidazolidin-1-yl, imidazolidin-2-yl, imidazolidin-4-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrroli Din-3-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl , 1,3-oxazolidin-3-yl, isothiazolidine, 1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidine- 1-yl, thiomorpholinyl, 1,2-tetrahydrothiazin-2-yl, 1,3-tetrahydrothiazin-3-yl, tetra Hydrothiadiazinyl, morpholinyl, 1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, 1,4-oxazin-2-yl, 1,2, 5-oxathiazin-4-yl and the like.

본 명세서에서 사용된 것으로서 질소 헤테로원자는 N=, >N 및 -NH를 의미하며, 여기에서 N=은 질소 이중결합을 나타내고, >N은 두개의 결합 연결부를 함유하는 질소를 나타내고, -N은 하나의 결합을 함유하는 질소를 나타낸다.As used herein, nitrogen heteroatoms mean N =,> N and -NH, where N = represents a nitrogen double bond,> N represents nitrogen containing two bond linkages, and -N is Nitrogen containing one bond is shown.

본 명세서에서 사용된 것으로서 "구체예"는 구별된 아속 (subgenera)으로의 화합물 또는 용도의 특정한 분족 (grouping)을 의미한다. 이러한 아속은 특정의 R1 또는 R3 기와 같은 하나의 특별한 치환체 따라서 인식할 수 있다. 그 밖의 다른 아 속은 R2가 수소이고 R1이 (C1-C6)알킬인 모든 화합물과 같이 다양한 치환체의 조합에 따라서 인식할 수 있다.As used herein, "specific example" means a specific grouping of a compound or use to a distinct subgenera. This subgenus can thus be recognized as one particular substituent, such as a particular R 1 or R 3 group. Other subgenus can be recognized depending on the combination of various substituents, such as all compounds in which R 2 is hydrogen and R 1 is (C 1 -C 6 ) alkyl.

따라서, 본 발명은 R3가 수소인 화학식 1의 화합물을 제공한다.Accordingly, the present invention provides a compound of formula 1, wherein R 3 is hydrogen.

본 발명은 또한, R3가 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 (여기에서, 상기의 -(C6-C10)아릴 또는 -(C1-C9)헤테로아릴은 -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)로 구성된 군으로부터 선택되는 화학식 1의 화합물을 제공한다.In the present invention, R 3 is halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl) 2 , -(C 3 -C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 1 -C 6) alkyl) (SO 2 (C 3 -C 6) cycloalkyl), -N ((C 3 -C 6) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl ), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3 -C 10 ) Cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl, - (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) alkyl -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3, -SO 2 NH 2, -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1- C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 are independently selected from the group consisting of the by 3 residues, optionally substituted - (C 6 -C 10) aryl, and - (C 1 -C 9) heteroaryl (wherein said - (C 6 -C 10) aryl or - (C 1 -C 9) heteroaryl group is a compound of formula 1 is selected from -S-, -O-, -N-, -NH- and -NR the group consisting of one to three elements selected from the group consisting of 12 is interposed optionally) to provide.

본 발명의 또 다른 구체예는 R3가 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1-C6)알킬-(C2-C9)헤테로사이클릴 (여기에서, 상기의 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1-C6)알킬-(C2-C9)헤테로사이클릴은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)로 구성된 군으로부터 선택되는 화학식 1의 화합물이다.Another embodiment of the invention provides that R 3 is halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl ) 2 ,-(C 3 -C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) Alkyl), -N ((C 1 -C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,- (CO) CF 3 ,-(CO) (C 3 -C 10 ) cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-( CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6- C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl,-(CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) alkyl, -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) Cycloalkyl, -SO 2 CF 3 , -SO 2 NH 2 , -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1 -C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 And-(C 3 -C 10 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl and-(optionally substituted with 1 to 3 residues independently selected from the group consisting of -SO 2 NR 5 R 6 C 1 -C 6 ) alkyl- (C 2 -C 9 ) heterocyclyl, wherein-(C 3 -C 10 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl and-(C 1 -C 6 ) alkyl- (C 2 -C 9 ) heterocyclyl consists of-(C = O), -SO 2 , -S-, -O-, -N-, -NH- and -NR 12 And one to three elements selected from the group are optionally interposed).

본 발명의 추가의 구체예는 R3가 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬 (여기에서, 상기의 -(C1-C6)알킬은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)인 화학식 1의 화합물이다.A further embodiment of the invention is provided that R 3 is halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl ) 2 ,-(C 3 -C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) Alkyl), -N ((C 1 -C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3- C 10 ) cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-( CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2- C 9) heterocyclyl, - (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1- C 6 ) alkyl-O (C 1 -C 6 ) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3 , -SO 2 NH 2 , -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1 -C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues selected from: wherein — (C 1 -C 6 ) alkyl is — (C═O), —SO 2 , —S Is optionally interrupted by 1 to 3 elements selected from the group consisting of-, -O-, -N-, -NH-, and -NR 12 ).

추가로, 본 발명은 하기 화학식 2의 화합물을 제공한다:In addition, the present invention provides a compound of Formula 2:

Figure 112006082893189-PCT00004
Figure 112006082893189-PCT00004

상기 식에서,Where

A는 하기 화학식의 기로 구성된 군으로부터 선택되며,A is selected from the group consisting of groups of the formula

Figure 112006082893189-PCT00005
Figure 112006082893189-PCT00005

Figure 112006082893189-PCT00006
Figure 112006082893189-PCT00006

여기에서 m은 0 내지 3의 정수이고, R13은 수소, 할로겐, 하이드록시, (C1-C6)-알킬, (C3-C7)-사이클로알킬, (C6-C10)-아릴, (C1-C9)헤테로아릴, (C2-C9)-헤테로사이클릴, O-(C1-C6)-알킬, O-(C3-C7)-사이클로알킬, SO2-(C1-C6)알킬, SO2(C3-C7)-사이클로알킬, NHSO2(C1-C6)알킬, N((C1-C6)알킬)(SO2(C1-C6-알킬)), N((C3-C7)사이클로 알킬(SO2(C1-C6-알킬)), N(C1-C6-알킬)(SO2(C3-C7)사이클로알킬), N((C3-C7)사이클로알킬)(SO2(C3-C7)사이클로알킬), OSO2(C1-C6)알킬, SO2CF3, SO2NH2, SO2NH(C1-C6)알킬, SO2NH(C3-C7)사이클로알킬, SO2NR5R6, SO2N((C1-C6)알킬)2, CF3, CO-(C1-C6)알킬, CO-(C3-C7)사이클로알킬, COCF3, CO2(C1-C6)알킬,

Figure 112006082893189-PCT00007
및
Figure 112006082893189-PCT00008
로 구성된 군으로부터 선택된 치환체이다.Where m is an integer from 0 to 3, R 13 is hydrogen, halogen, hydroxy, (C 1 -C 6 ) -alkyl, (C 3 -C 7 ) -cycloalkyl, (C 6 -C 10 )- Aryl, (C 1 -C 9 ) heteroaryl, (C 2 -C 9 ) -heterocyclyl, O- (C 1 -C 6 ) -alkyl, O- (C 3 -C 7 ) -cycloalkyl, SO 2- (C 1 -C 6 ) alkyl, SO 2 (C 3 -C 7 ) -cycloalkyl, NHSO 2 (C 1 -C 6 ) alkyl, N ((C 1 -C 6 ) alkyl) (SO 2 ( C 1 -C 6 -alkyl)), N ((C 3 -C 7 ) cycloalkyl (SO 2 (C 1 -C 6 -alkyl)), N (C 1 -C 6 -alkyl) (SO 2 (C 3 -C 7 ) cycloalkyl), N ((C 3 -C 7 ) cycloalkyl) (SO 2 (C 3 -C 7 ) cycloalkyl), OSO 2 (C 1 -C 6 ) alkyl, SO 2 CF 3 , SO 2 NH 2 , SO 2 NH (C 1 -C 6 ) alkyl, SO 2 NH (C 3 -C 7 ) cycloalkyl, SO 2 NR 5 R 6 , SO 2 N ((C 1 -C 6 ) alkyl ) 2 , CF 3 , CO- (C 1 -C 6 ) alkyl, CO- (C 3 -C 7 ) cycloalkyl, COCF 3 , CO 2 (C 1 -C 6 ) alkyl,
Figure 112006082893189-PCT00007
And
Figure 112006082893189-PCT00008
Substituent selected from the group consisting of.

본 발명의 또 다른 구체예는 하기 화학식 3의 화합물이다:Another embodiment of the invention is a compound of formula

Figure 112006082893189-PCT00009
Figure 112006082893189-PCT00009

상기 식에서, B는 하기 화학식의 기들로 구성된 군으로부터 선택된다:Wherein B is selected from the group consisting of groups of the formula:

Figure 112006082893189-PCT00010
Figure 112006082893189-PCT00010

또한, 화학식 4의 화합물이 제공된다:Also provided are compounds of formula 4:

Figure 112006082893189-PCT00011
Figure 112006082893189-PCT00011

상기 식에서, D는 하기 화학식의 기들로 구성된 군으로부터 선택되며,Wherein D is selected from the group consisting of groups of the formula

Figure 112006082893189-PCT00012
Figure 112006082893189-PCT00012

Figure 112006082893189-PCT00013
Figure 112006082893189-PCT00013

여기에서 q는 1 내지 2의 정수이다.Q is an integer of 1 to 2 here.

본 발명의 추가의 구체예는 하기 화학식 5의 화합물이다:A further embodiment of the invention is a compound of formula

Figure 112006082893189-PCT00014
Figure 112006082893189-PCT00014

상기 식에서, E는 하기 화학식의 기로 구성된 군으로부터 선택되며,Wherein E is selected from the group consisting of groups of the formula

Figure 112006082893189-PCT00015
Figure 112006082893189-PCT00015

여기에서 R14는 (C1-C6)-알킬, (C3-C7)-사이클로알킬 및 (C2-C9)-헤테로사이클릴로 구성된 군으로부터 선택되고, R15는 수소, (C1-C6)-알킬, (C3-C7)-사이클로알킬 및 (C2-C9)-헤테로사이클릴로 구성된 군으로부터 선택된다.Where R 14 is (C 1 -C 6) - alkyl, (C 3 -C 7) - cycloalkyl and (C 2 -C 9) - is selected from the group consisting of heterocycle reels, R 15 is hydrogen, (C 1 -C 6 ) -alkyl, (C 3 -C 7 ) -cycloalkyl and (C 2 -C 9 ) -heterocyclyl.

따라서, 본 발명은 R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되는 화학식 1의 화합물을 제공한다.Thus, the present invention provides that R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 It provides a compound of Formula 1 selected from-(C 1 -C 6 ) alkyl.

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl to provide a compound of formula 1.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되는 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and — (C 2 -C 9 ) heterocyclyl provide a compound of Formula 1 selected from the group consisting of:

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되는 화학식 1의 화합물을 고려한다. 바람직한 구체예에서, R1은 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬이다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Consider a compound of formula 1 selected from —C 6 ) alkyl, —O (C 3 -C 7 ) cycloalkyl, and —O (C 2 -C 9 ) heterocyclyl. In a preferred embodiment, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 is a compound of Formula 1

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6로부터 선택된 화학식 1의 화합물이다. 바람직한 구체예에서, R1은 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SO2NR5R6이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 . In a preferred embodiment, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -SO 2 NR 5 optionally substituted by 1-3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 .

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환 된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6, 또는 -NR12SO2R7인 화학식 1의 화합물을 제공한다. 바람직한 구체예에서, R1은 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR12SO2R7이다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 , or -NR 12 SO 2 R 7 . In a preferred embodiment, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -NR 12 SO 2 optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 7 .

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있는 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6) alkenyl and - (C 2 -C 6) alkynyl R 2 moieties are provided compounds of formula (I) which may be optionally substituted by one to three groups R 12.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6) 알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있는 화학식 1의 화합물이 제공된다.Further, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted with 1 to 3 R 12 groups Compounds of are provided.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기 는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있는 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and , where the - (C 2 -C 6) alkenyl and - (C 2 -C 6) a compound of formula (I) which alkynyl R 2 moieties may be optionally substituted by one to three groups R 12.

또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있는 화학식 1의 화합물이 제공된다.R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo Optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8- ( C 1 -C 6 ) alkyl; R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 ,-(C 1 -C 6 ) alkyl optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 , wherein said-(C 2 -C 6) alkenyl and - (C 2 -C 6) alkynyl R 2 moieties are provided compounds of formula (I) which may be optionally substituted by one to three groups R 12.

본 발명은 추가로, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2가 수소인 화학식 1의 화합물을 제공한다.The present invention further provides that R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3- C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 optionally selected from 1 to 3 residues independently selected from the group consisting of Substituted-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein R 2 is hydrogen.

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 수소인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein R 2 is hydrogen.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 수소인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; Provided is a compound of Formula 1, wherein R 2 is hydrogen.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되며; R2가 수소인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; Provided is a compound of Formula 1, wherein R 2 is hydrogen.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 수소인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 ; R 2 is hydrogen.

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 수소인 화 학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; Is a compound of Formula 1 wherein R 2 is hydrogen.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 수소인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 and R 6 -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; Provided is a compound of Formula 1, wherein R 2 is hydrogen.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 수소인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; Provided is a compound of Formula 1, wherein R 1 is hydrogen.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 수소인 화학식 1의 화합물이 제공된다.Additionally, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; Provided is a compound of Formula 1, wherein R 1 is hydrogen.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 수소인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is hydrogen;

본 발명은 또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 -(C1-C6)알킬인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Selected from-(C 1 -C 6 ) alkyl; R 2 provides a compound of Formula 1 wherein-(C 1 -C 6 ) alkyl.

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 -(C1-C6)알킬인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein R 2 is — (C 1 -C 6 ) alkyl.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 -(C1-C6)알킬인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; Provided is a compound of Formula 1, wherein R 2 is — (C 1 -C 6 ) alkyl.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되며; R2가 -(C1-C6)알킬인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; Provided is a compound of Formula 1, wherein R 2 is — (C 1 -C 6 ) alkyl.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 -(C1-C6)알킬인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 ; R 2 is-(C 1 -C 6 ) alkyl.

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 -(C1-C6)알킬인 화학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; R 2 is-(C 1 -C 6 ) alkyl.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 -(C1-C6)알킬인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 and R 6 -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; Provided is a compound of Formula 1, wherein R 2 is — (C 1 -C 6 ) alkyl.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; There is provided a compound of Formula 1, wherein R 1 is-(C 1 -C 6 ) alkyl.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬인 화학식 1의 화합물이 제공된다.Additionally, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; There is provided a compound of Formula 1, wherein R 1 is-(C 1 -C 6 ) alkyl.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 -(C1-C6)알킬인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is — (C 1 -C 6 ) alkyl.

본 발명은 또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있으며; n은 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Selected from-(C 1 -C 6 ) alkyl; R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 ,-(C 1 -C 6 ) alkyl optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 , wherein said-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; n is 1 to provide a compound of formula 1

본 발명은 추가로, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되고; R2가 -(C1-C6)알킬이며; n은 1인 화학식 1의 화합물을 제공한다.The present invention further provides that R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3- C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 optionally selected from 1 to 3 residues independently selected from the group consisting of Substituted-(C 1 -C 6 ) alkyl; R 2 is-(C 1 -C 6 ) alkyl; n is 1 to provide a compound of formula 1

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 -(C1-C6)알킬이며; n이 1인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알 킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물이다.One embodiment of the invention provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -NR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 5 R 6 ; R 2 is-(C 1 -C 6 ) alkyl; n is 1;

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; R 2 is-(C 1 -C 6 ) alkyl; n is 1;

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 and R 6 -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며; n은 1인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is — (C 1 -C 6 ) alkyl; There is provided a compound of Formula 1, wherein n is 1.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며; n은 1인 화학식 1의 화합물이 제공된다.Additionally, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is — (C 1 -C 6 ) alkyl; There is provided a compound of Formula 1, wherein n is 1.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 -(C1-C6)알킬이며; n이 1인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is-(C 1 -C 6 ) alkyl; n is 1;

본 발명은 또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 -(C1-C6)알킬이고; n은 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Selected from-(C 1 -C 6 ) alkyl; R 2 is — (C 1 -C 6 ) alkyl; n is 1 to provide a compound of formula 1

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 -(C1-C6)알킬이며; n이 1인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 ; R 2 is-(C 1 -C 6 ) alkyl; n is 1;

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 -(C1-C6)알 킬이고; n이 1인 화학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; R 2 is — (C 1 -C 6 ) alkyl; n is 1;

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 -(C1-C6)알킬이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 and R 6 -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 1.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며, n은 1인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; Provided is a compound of Formula 1, wherein R 1 is-(C 1 -C 6 ) alkyl and n is 1.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며; n은 1인 화학식 1의 화합물이 제공된다.Additionally, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is — (C 1 -C 6 ) alkyl; There is provided a compound of Formula 1, wherein n is 1.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 -(C1-C6)알킬이며; n이 1인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is-(C 1 -C 6 ) alkyl; n is 1;

본 발명은 또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있으며; n은 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Selected from-(C 1 -C 6 ) alkyl; R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 ,-(C 1 -C 6 ) alkyl optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 , wherein said-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; n is 1 to provide a compound of formula 1

본 발명은 추가로, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되고; R2가 수소이며; n은 1인 화학식 1의 화합물을 제공한다.The present invention further provides that R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3- C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 optionally selected from 1 to 3 residues independently selected from the group consisting of Substituted-(C 1 -C 6 ) alkyl; R 2 is hydrogen; n is 1 to provide a compound of formula 1

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 수소이며; n이 1인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 1.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환 된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 수소이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 1.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되며; R2가 수소이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 1.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 수소이고; n이 1인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 ; R 2 is hydrogen; n is 1;

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 수소이고; n이 1인 화학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; R 2 is hydrogen; n is 1;

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 수소이고; n이 1인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 and R 6 -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 1.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 수소이며, n은 1인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; Provided is a compound of Formula 1, wherein R 1 is hydrogen and n is 1.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 수소이며; n은 1인 화학식 1의 화합물이 제공된다.Additionally, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is hydrogen; There is provided a compound of Formula 1, wherein n is 1.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 수소이며; n이 1인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is hydrogen; n is 1;

본 발명은 또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있으며; n은 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Selected from-(C 1 -C 6 ) alkyl; R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 ,-(C 1 -C 6 ) alkyl optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 , wherein said-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; n provides 2 compounds of formula 1

본 발명은 추가로, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되고; R2가 -(C1-C6)알킬이며; n은 2인 화학식 1의 화합물을 제공한다.The present invention further provides that R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3- C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 optionally selected from 1 to 3 residues independently selected from the group consisting of Substituted-(C 1 -C 6 ) alkyl; R 2 is-(C 1 -C 6 ) alkyl; n provides 2 compounds of formula 1

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 -(C1-C6)알킬이며; n이 2인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 ; R 2 is-(C 1 -C 6 ) alkyl; n is 2;

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; R 2 is-(C 1 -C 6 ) alkyl; n is 2;

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 and R 6 -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며, n은 2인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; Provided is a compound of Formula 1, wherein R 1 is-(C 1 -C 6 ) alkyl and n is 2.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며; n은 2인 화학식 1의 화합물이 제공된다.Additionally, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is — (C 1 -C 6 ) alkyl; There is provided a compound of Formula 1, wherein n is 2.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 -(C1-C6)알킬이며; n이 2인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is-(C 1 -C 6 ) alkyl; n is 2;

본 발명은 또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 -(C1-C6)알킬이고; n은 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Selected from-(C 1 -C 6 ) alkyl; R 2 is — (C 1 -C 6 ) alkyl; n provides 2 compounds of formula 1

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 -(C1-C6)알킬이며; n이 2인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되 며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 ; R 2 is-(C 1 -C 6 ) alkyl; n is 2;

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; R 2 is-(C 1 -C 6 ) alkyl; n is 2;

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환 된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 -(C1-C6)알킬이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; R 2 is-(C 1 -C 6 ) alkyl; Provided is a compound of Formula 1, wherein n is 2.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며, n은 2인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; Provided is a compound of Formula 1, wherein R 1 is-(C 1 -C 6 ) alkyl and n is 2.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 -(C1-C6)알킬이며; n은 2인 화학식 1의 화합물이 제공된다.Additionally, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is — (C 1 -C 6 ) alkyl; There is provided a compound of Formula 1, wherein n is 2.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 -(C1-C6)알킬이며; n이 2인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 12 or -CONR 5 R 6 by independently selected 1-3 residue optionally substituted from the group consisting of 7, and Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is-(C 1 -C 6 ) alkyl; n is 2;

본 발명은 또한, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되며; R2는 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있으며; n은 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) optionally substituted by one to three residues independently selected from the group consisting of cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 Selected from-(C 1 -C 6 ) alkyl; R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 ,-(C 1 -C 6 ) alkyl optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 , wherein said-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; n provides 2 compounds of formula 1

본 발명은 추가로, R1이 수소, 하이드록시, 및 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬로부터 선택되고; R2가 수소이며; n은 2인 화학식 1의 화합물을 제공한다.The present invention further provides that R 1 is hydrogen, hydroxy, and hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3- C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 optionally selected from 1 to 3 residues independently selected from the group consisting of Substituted-(C 1 -C 6 ) alkyl; R 2 is hydrogen; n provides 2 compounds of formula 1

본 발명은 추가로, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이고; R2가 수소이며; n이 2인 화학식 1의 화합물을 제공한다.The invention further provides that R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6 and -CONR 5 R 8 by one to three moieties independently selected from the group consisting of an optionally substituted - (C 1 -C 6 ) alkyl; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 2.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택되며; R2가 수소이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- -(C 3 -optionally substituted by 1 to 3 residues independently selected from the group consisting of (C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 2.

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8 로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -O(C1-C6)알킬, -O(C3-C7)사이클로알킬 및 -O(C2-C9)헤테로사이클릴로부터 선택되며; R2가 수소이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9 ) -O (C 1 optionally substituted by 1 to 3 residues independently selected from the group consisting of heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl and -O (C 2 -C 9 ) heterocyclyl; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 2.

본 발명의 한가지 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -NR5R6이며; R2가 수소이고; n이 2인 화학식 1의 화합물이다.One embodiment of the invention wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl -NR 5 optionally substituted by 1 to 3 residues independently selected from the group consisting of-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 R 6 ; R 2 is hydrogen; n is 2;

본 발명의 추가의 구체예는 R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -SR7, -SOR7, -SO2R7 및 -SO2NR5R6으로부터 선택되며; R2가 수소이고; n이 2인 화학식 1의 화합물이다.A further embodiment of the invention is an embodiment wherein R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cyclo -SR optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 and -CONR 5 R 8 7 , -SOR 7 , -SO 2 R 7 and -SO 2 NR 5 R 6 ; R 2 is hydrogen; n is 2;

본 발명은 또한, R1이 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R12, -CONR5R6, -NHCOR12, -NR12CONR5R6 또는 -NR12SO2R7이며; R2가 수소이고; n이 2인 화학식 1의 화합물을 제공한다.In the present invention, R 1 is hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,- (C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 and R 6 -CONR 5 R 8 group of -CO 2 R 12 by one to three moieties independently selected from optionally substituted consisting of , -CONR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 or -NR 12 SO 2 R 7 ; R 2 is hydrogen; Provided is a compound of Formula 1, wherein n is 2.

또한, R2가 수소, 또는 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 수소이며, n은 2인 화학식 1의 화합물이 제공된다.And R 2 is hydrogen or hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, - NHCOR 12 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 — (C 1 -C 6 ) alkyl optionally substituted by one to three residues independently selected from the group consisting of: (C 2 -C 6 ) alkenyl and — (C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; Provided is a compound of Formula 1, wherein R 1 is hydrogen and n is 2.

추가로, R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6) 알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C7)사이클로알킬 또는 -(C2-C9)헤테로사이클릴이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1은 수소이며; n은 2인 화학식 1의 화합물이 제공된다.Further, R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alky carbonyl, -C = N-OH, -C = NO ((C 1 -C 6) alkyl), -NR 5 R 6, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 - C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 -(C 3 -C 7 ) cycloalkyl or-(C 2 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is hydrogen; There is provided a compound of Formula 1, wherein n is 2.

본 발명의 또 다른 구체예는 R2가 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -CO2R5 또는 -CONR5R6이며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기 는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; R1이 수소이며; n이 2인 화학식 1의 화합물이다.In another embodiment of the invention R 2 is hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 R 6, -NHCOR 12, -NR 12 CONR 5 R 6 and -NR 12 SO 2 R a -CO 2 R 5 or -CONR 5 R 6 group independently selected by one to three moieties from the optionally substituted 7 and consisting of Wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl R 2 residues may be optionally substituted by 1 to 3 R 12 groups; R 1 is hydrogen; n is 2;

본 발명은 또한, R1 및 R2가 이들이 부착된 원자(들)과 함께 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C10)사이클로알킬을 형성하며, 여기에서 상기 사이클릭 기의 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있는 화학식 1의 화합물을 제공한다.The present invention also provides that R 1 and R 2 together with the atom (s) to which they are attached are hydrogen, halogen, hydroxy, —NO 2 , —CN, — (C 1 -C 6 ) alkyl, — (C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-( C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 -(C optionally substituted by 1 to 3 residues independently selected from the group consisting of R 7 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 3 -C 10 ) cycloalkyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl residues of the cyclic group are selected from 1 to 3 R 12 groups Provided are compounds of Formula 1, which may be optionally substituted.

본 발명은 추가로 R1 및 R2가 이들이 부착된 원자(들)과 함께 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C2-C9)헤테로사이클릴을 형성하며, 여기에서 상기 사이클릭 기의 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있는 화학식 1의 화합물을 제공한다.The present invention further provides that R 1 and R 2 together with the atom (s) to which they are attached are hydrogen, halogen, hydroxy, -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-( C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 -(C optionally substituted by 1 to 3 residues independently selected from the group consisting of R 7 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 2 -C 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl residues of the cyclic group are present in groups of 1 to 3 R 12 Provided are compounds of Formula 1, which may be optionally substituted by

본 발명은 또한, R1 및 R2가 이들이 부착된 원자(들)과 함께 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C10)사이클로알킬을 형성하며, 여기에서 상기 사이클릭 기의 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; n은 1인 화학식 1의 화합물을 제공한다.The present invention also provides that R 1 and R 2 together with the atom (s) to which they are attached are hydrogen, halogen, hydroxy, —NO 2 , —CN, — (C 1 -C 6 ) alkyl, — (C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-( C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 -(C optionally substituted by 1 to 3 residues independently selected from the group consisting of R 7 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 3 -C 10 ) cycloalkyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl residues of the cyclic group are selected from 1 to 3 R 12 groups Optionally substituted; n is 1 to provide a compound of formula 1

본 발명은 또한, R1 및 R2가 이들이 부착된 원자(들)과 함께 수소, 할로겐, 하이드록시, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C2-C9)헤테로사이클릴을 형성하며, 여기에서 상기 사이클릭 기의 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고; n은 1인 화학식 1의 화합물을 제공한다.The present invention also provides that R 1 and R 2 together with the atom (s) to which they are attached are hydrogen, halogen, hydroxy, —NO 2 , —CN, — (C 1 -C 6 ) alkyl, — (C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-( C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 -(C optionally substituted by 1 to 3 residues independently selected from the group consisting of R 7 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 2 -C 9 ) heterocyclyl, wherein the-(C 2 -C 6 ) alkenyl and-(C 2 -C 6 ) alkynyl residues of the cyclic group are present in groups of 1 to 3 R 12 Optionally substituted by; n is 1 to provide a compound of formula 1

바람직한 구체예에서, R4는 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택된 치환체이고, 여기에서 상기의 -(C1-C6)알킬, -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴 R4 치환체는 수소, 할로겐, 하이드록시, -(C1-C6)알킬, -CN, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 단 전술한 R4 치환체의 헤테로원자는 또 다른 헤테로원자에 결합된 sp3 탄소원자에 결합되지 않을 수 있고, 여기에서 상 기 -CONR5R8 기의 R5 및 R8은 이들이 부착된 원자와 함께 -(C3-C10)사이클로알킬 또는 -(C2-C9)헤테로사이클릴을 형성할 수 있다.In a preferred embodiment, R 4 is a substituent selected from the group consisting of hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl, wherein Wherein-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl R 4 substituents are hydrogen, halogen, hydroxy,-(C 1 -C 6 ) alkyl, -CN, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 and -CONR Optionally substituted with 1 to 3 residues independently selected from the group consisting of 5 R 8 , provided that the heteroatom of the aforementioned R 4 substituent may not be bonded to an sp 3 carbon atom bonded to another heteroatom, wherein Wherein R 5 and R 8 of the —CONR 5 R 8 group together with the atoms to which they are attached may form — (C 3 -C 10 ) cycloalkyl or — (C 2 -C 9 ) heterocyclyl.

추가의 바람직한 구체예에서, R4는 수소이다.In a further preferred embodiment, R 4 is hydrogen.

추가로, 본 발명은 R5 및 R6이 각각 상술한 바와 같이 수소 및 치환된 -(C1-C6)알킬로 구성된 군으로부터 독립적으로 선택된 치환체인 화학식 1의 화합물을 제공한다.In addition, the present invention provides compounds of Formula 1, wherein R 5 and R 6 are each independently a substituent selected from the group consisting of hydrogen and substituted-(C 1 -C 6 ) alkyl as described above.

본 발명의 특정한 구체예는 하기 화합물들로부터 선택된 화합물이다:Particular embodiments of the invention are compounds selected from the following compounds:

N-(1-메틸-1-페닐-에틸)-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤젠설폰아미드;N- (1-Methyl-1-phenyl-ethyl) -3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyri Midin-4-ylamino] -methyl} -benzenesulfonamide;

3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤젠설폰아미드;3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -benzenesulfonamide ;

5-{4-[3-(트리플루오로-메탄설포닐)-벤질아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [3- (trifluoro-methanesulfonyl) -benzylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one ;

5-{4-[(피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸- 피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl) -methanesulfonamide;

3-옥소-3-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피페리딘-1-일)-프로피오니트릴;3-oxo-3- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -piperidin-1-yl) -propionitrile;

5-{4-[3-(1,1-디옥소-1N6-이소티아졸리딘-2-일)-프로필아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [3- (1,1-Dioxo-1N 6 -isothiazolidin-2-yl) -propylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1 , 3-dihydro-indol-2-one;

5-[4-(2-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-메탄설포닐-피페리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl} -methane Sulfonamides;

N-{4-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-부틸}-메탄설폰아미드;N- {4- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -butyl} -methane Sulfonamides;

5-{4-[(1-메탄설포닐-피페리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -methanesulfonamide;

메탄설폰산 3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐 에스테르;Methanesulfonic acid 3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl esters;

N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N- {3- [2- (2-Oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl} -methane Sulfonamides;

5-{4-[(4-메탄설포닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

N-(4-플루오로-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-페닐}-메탄설폰아미드;N- (4-Fluoro-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Phenyl} -methanesulfonamide;

5-{4-[(5-옥소-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-oxo-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On;

N-(4-메톡시-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (4-methoxy-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide;

N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

5-[4-(3-메탄설포닐메틸-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(4-트리플루오로아세틸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-trifluoroacetyl-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On;

5-{4-[(1-메탄설포닐-아제티딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-azetidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

N-메틸-N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

5-{4-[(1-메탄설포닐-피폴리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -methanesulfonamide;

5-{4-[2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

5-{4-[(4-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

{2,2-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-카밤산 tert-부틸 에스테르;{2,2-Dimethyl-3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -carbamic acid tert-butyl ester;

5-[4-(3-이소프로폭시-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-isopropoxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-메틸-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(테트라하이드로-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(tetrahydro-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-[4-(2-에틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-ethyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(테트라하이드로-푸란-2R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(tetrahydro-furan-2R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(테트라하이드로-푸란-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(tetrahydro-furan-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(5-메틸-푸란-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-methyl-furan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one ;

5-{4-[(1-메탄설포닐-피롤리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(아다만탄-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(adamantan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(아다만탄-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(adamantan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-[4-(2-메톡시-2-메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methoxy-2-methyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(엔도-비사이클로[2.2.1]헵트-5-엔-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(endo-bicyclo [2.2.1] hept-5-en-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indol-2-one;

(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤질)-포스폰산 디메틸 에스테르;(3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -benzyl) Phosphonic acid dimethyl ester;

5-[4-(3-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(2-하이드록시-사이클로헥실메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-hydroxycyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

N-(4-메톡시-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (4-methoxy-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide;

5-{4-[(4-에탄설포닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-ethanesulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

5-(4-{[4-(프로판-2-설포닐)-모르폴린-2-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-{[4- (Propan-2-sulfonyl) -morpholin-2-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino) -1,3- Dihydro-indol-2-one;

5-{4-[(4-아세틸-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-acetyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On;

5-{4-[(4-프로피오닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-propionyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-(4-{[4-(2,2-디메틸-프로피오닐)-모르폴린-2-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-{[4- (2,2-dimethyl-propionyl) -morpholin-2-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino) -1, 3-dihydro-indol-2-one;

2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-모르폴린-4-카복실산 메틸 에스테르;2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -morpholine- 4-carboxylic acid methyl ester;

5-{4-[(4-메톡시아세틸-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-methoxyacetyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

5-[4-(3-에탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-ethanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(4-메탄설포닐-모르폴린-2R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-morpholine-2R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

5-{4-[(4-메탄설포닐-모르폴린-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-morpholin-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

5-{4-[(피리미딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(pyrimidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(피라진-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(pyrazin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

N-(4-플루오로-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (4-Fluoro-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide;

5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(4-이소부티릴-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-isobutyryl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

5-[4-(3,3-디메틸-2-옥소-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3,3-dimethyl-2-oxo-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1,2-디메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1,2-dimethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(2-메톡시-1-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methoxy-1-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[2-(1,1-디옥소-1D6-이소티아졸리딘-2-일)-에틸아미노]-5-트리플루오로 메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1,1-Dioxo-1D 6 -isothiazolidin-2-yl) -ethylamino] -5-trifluoro methyl-pyrimidin-2-ylamino} -1 , 3-dihydro-indol-2-one;

5-[4-(3-메틸아미노-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methylamino-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(6-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(6-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[3-(1,1-디옥소-1,l,6-이소티아졸리딘-2-일)-벤질아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [3- (1,1-Dioxo-1, l, 6-isothiazolidin-2-yl) -benzylamino] -5-trifluoromethyl-pyrimidin-2-ylamino } -1,3-dihydro-indol-2-one;

5-[4-(1R-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1R-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-(4-이소프로필아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-isopropylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

5-(4R-이급-부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4R-Second-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

5-(4S-이급-부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4S-Second-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

5-[4-(2-메틸아미노-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methylamino-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1S-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3- 디하이드로-인돌-2-온;5- [4- (1S-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(2-메탄설포닐메틸-티아졸-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-methanesulfonylmethyl-thiazol-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-(4-프로필아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-propylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

5-[4-(2-하이드록시-1-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-hydroxy-1-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1-하이드록시메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(5-메탄설포닐-피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-methanesulfonyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(피리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(pyridin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-[4-(1,3-디메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1,3-dimethyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-이소프로필-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-isopropyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Propyl} -methanesulfonamide;

5-[4-(1S-하이드록시메틸-2-메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1S-hydroxymethyl-2-methyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-사이클로헥실-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-cyclohexyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide;

5-[4-(1,2,3,4-테트라하이드로-나프탈렌-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1,2,3,4-tetrahydro-naphthalen-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole- 2-one;

5-{4-[(1-메탄설포닐-피롤리딘-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(3-메틸-티오펜-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(3-methyl-thiophen-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On;

5-{4-[(1-메탄설포닐-피롤리딘-3R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-3R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-[4-(2-하이드록시-1S-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-hydroxy-1S-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(2-하이드록시-1S-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-hydroxy-1S-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1R-하이드록시메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1R-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1-피리미딘-4-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1-pyrimidin-4-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1,1-디옥소-테트라하이드로-1-티오펜-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1,1-Dioxo-tetrahydro-1-thiophen-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro- Indol-2-one;

5-{4-[(1H-이미다졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아 미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1H-imidazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-[4-(2-피페리딘-2-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-piperidin-2-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(이소부틸-메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (isobutyl-methyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-메틸}-페닐}-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -Methyl} -phenyl} -methanesulfonamide;

N-에틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-ethyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

5-[4-(2-메탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-이소프로필-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-isopropyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide;

5-{4-[(3,4,5,6-테트라하이드로-2H-[1,2']비피리디닐-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2 -Ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(1-피리미딘-2-일-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-pyrimidin-2-yl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

5-{4-[2R-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2R- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

5-{4-[2S-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피 리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2S- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

5-[4-(3-메틸설파닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methylsulfanyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1S-하이드록시메틸-3-메틸설파닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1S-hydroxymethyl-3-methylsulfanyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one ;

5-[4-(2-하이드록시-1R-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-hydroxy-1R-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1R-하이드록시메틸-2-메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1R-hydroxymethyl-2-methyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-에틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-ethyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -methanesulfonamide;

5-{4-[(1-메탄설포닐-피롤리딘-3R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노]}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-3R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino]}-1,3-dihydro- Indol-2-one;

5-[4-(1S-하이드록시메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1S-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(3,5-디니트로-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3,5-Dinitro-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl) -methanesulfonamide;

N-이소프로필-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리 플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;N-isopropyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Ethyl} -methanesulfonamide;

5-[4-(2-하이드록시-1-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-hydroxy-1-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1R-하이드록시메틸-3-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1R-hydroxymethyl-3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(1S-하이드록시메틸-3-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1S-hydroxymethyl-3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-메탄설포닐-피페리딘-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(1-메탄설포닐-피롤리딘-2R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-2R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-[4-(메틸-피리딘-2-일메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (methyl-pyridin-2-ylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(3-메탄설포닐-벤질)-메틸-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(3-Methanesulfonyl-benzyl) -methyl-amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

5-[4-(메틸-피리딘-3-일메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (methyl-pyridin-3-ylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-메틸-아미노]-5-트리플루오로메틸- 피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -methyl-amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

5-[4-(메틸-피리딘-4-일메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (methyl-pyridin-4-ylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-(4-사이클로펜틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-cyclopentylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

5-[4-(2,6-디메톡시-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2,6-dimethoxy-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1,5-디메틸-1H-피라졸-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온; 및5- {4-[(1,5-Dimethyl-1H-pyrazol-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indol-2-one; And

5-[4-(2-이미다졸-1-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온.5- [4- (2-imidazol-1-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one.

본 발명의 특정한 바람직한 구체예는 하기 화합물들로부터 선택된 화합물이다:Particularly preferred embodiments of the invention are compounds selected from the following compounds:

5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -methanesulfonamide;

N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -methanesulfonamide;

5-{4-[2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피 리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

5-{4-[(비사이클로[2.2.1]헵트-5-엔-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(Bicyclo [2.2.1] hept-5-en-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

5-[4-(3-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-이소프로필-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-isopropyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Propyl} -methanesulfonamide;

N-사이클로헥실-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-cyclohexyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Propyl} -methanesulfonamide;

5-{4-[2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

N-이소프로필-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;N-isopropyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Ethyl} -methanesulfonamide;

5-{4-[(1-메탄설포닐-피롤리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-(4-사이클로펜틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-cyclopentylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

에탄설폰산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리 플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;Methyl ethanesulfonic acid- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl }-amides;

2,2,2-트리플루오로-N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아세트아미드;2,2,2-trifluoro-N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl -Pyrimidin-4-ylamino] -propyl} -acetamide;

N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -methanesulfonamide;

5-(4-사이클로부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-cyclobutylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

5-{4-[2-하이드록시-2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2-hydroxy-2- (1-methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1 , 3-dihydro-indol-2-one;

3-옥소-3-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피페리딘-1-일)-프로피오니트릴;3-oxo-3- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -piperidin-1-yl) -propionitrile;

5-{4-[(1-메탄설포닐-피페리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(4-메탄설포닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

5-{4-[(5-옥소-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-oxo-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On;

5-{4-[(1-메탄설포닐-피롤리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-[4-(3-이소프로폭시-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미 노]-1,3-디하이드로-인돌-2-온;5- [4- (3-isopropoxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(아다만탄-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(adamantan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

N-{2,2-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N- {2,2-dimethyl-3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide;

5-{4-[(1-하이드록시-사이클로펜틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(4-하이드록시-테트라하이드로-피란-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-hydroxy-tetrahydro-pyran-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(2-하이드록시-사이클로헥실메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-hydroxycyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-[4-(3-메탄설포닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-피리미딘-2-일-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-pyrimidin-2-yl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로피온산 에틸 에스테르;3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propionic acid ethyl ester;

5-{4-[(1-에틸-5-옥소-피롤리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-ethyl-5-oxo-pyrrolidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

2,N-디메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플 루오로메틸-피리미딘-4-일아미노]-에틸}-부티르아미드;2, N-dimethyl-N- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -butyramide;

2-메톡시-N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아세트아미드;2-methoxy-N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -propyl} -acetamide;

5-{4-[2-(1-아세틸-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1-acetyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(1-메탄설포닐-피페리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(1-메탄설포닐-피롤리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(1-피리미딘-2-일-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-pyrimidin-2-yl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤젠설폰아미드;3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -benzenesulfonamide ;

N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-메탄설폰아미드;N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Methanesulfonamide;

N-(4-메톡시-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (4-methoxy-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide;

5-[4-(3-메탄설포닐메틸-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-메틸-N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -methyl} -phenyl) -methanesulfonamide;

5-{4-[(4-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(5-메틸-푸란-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-methyl-furan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one ;

(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤질)-포스폰산 디메틸 에스테르;(3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -benzyl) Phosphonic acid dimethyl ester;

5-{4-[(피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-[5-트리플루오로메틸-4-(2-트리플루오로메틸-벤질아미노)-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [5-trifluoromethyl-4- (2-trifluoromethyl-benzylamino) -pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-[4-(3-에탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- [4- (3-ethanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(피리미딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(pyrimidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(피라진-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(pyrazin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

N-(4-플루오로-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (4-Fluoro-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide;

5-{4-[(피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노} -1,3-디하이드로-인돌-2-온;5- {4-[(pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[(6-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(6-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(2-메탄설포닐메틸-티아졸-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-methanesulfonylmethyl-thiazol-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(5-메탄설포닐-피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-methanesulfonyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(3-메틸-티오펜-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(3-methyl-thiophen-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On;

5-{4-[(1H-이미다졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1H-imidazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

5-[4-(2-메탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl) -methanesulfonamide;

N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

5-{4-[(1,5-디메틸-1H-피라졸-3-일메틸)-아미노]-5-트리플루오로메틸-피리미 딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1,5-Dimethyl-1H-pyrazol-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

5-[4-(2-이미다졸-1-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-imidazol-1-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

5-{4-[(3-메틸-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(3-methyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one ;

5-[4-(3-메탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(이소크로만-1-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(isochroman-1-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[2-(피리딘-3-일옥시)-프로필아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (pyridin-3-yloxy) -propylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[2-(6-메틸-피리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (6-Methyl-pyridin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(2,3-디하이드로-벤조[1,4]디옥신-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2,3-dihydro-benzo [1,4] dioxin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one;

5-{4-[2-(4-메틸-1H-이미다졸-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (4-Methyl-1H-imidazol-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indol-2-one;

5-{4-[2-(1H-벤조이미다졸-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘- 2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1H-Benzoimidazol-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin- 2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(5-페닐-4H-[1,2,4]트리아졸-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-phenyl-4H- [1,2,4] triazol-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one;

5-{4-[(3-메틸-이미다조[2,1-b]티아졸-6-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(3-methyl-imidazo [2,1-b] thiazol-6-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one;

N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (2-Methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

N-(3-메탄설포닐아미노-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-메틸}-페닐)-메탄설폰아미드; 및N- (3-methanesulfonylamino-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-2- Monoamino] -methyl} -phenyl) -methanesulfonamide; And

N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드.N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide.

본 발명의 바람직한 구체예는 하기 화합물들로부터 선택된다:Preferred embodiments of the invention are selected from the following compounds:

5-[4-(3-메탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

에탄설폰산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;Methyl ethanesulfonic acid- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl }-amides;

5-{4-[(이소크로만-1-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(isochroman-1-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[2-(피리딘-3-일옥시)-프로필아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (pyridin-3-yloxy) -propylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤젠설폰아미드;3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -benzenesulfonamide ;

5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl) -methanesulfonamide;

N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -methanesulfonamide;

5-{4-[(4-메탄설포닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

5-[4-(3-메탄설포닐메틸-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-메탄설포닐-피롤리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -methanesulfonamide;

5-{4-[2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

5-{4-[(4-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(4-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-[4-(3-이소프로폭시-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-isopropoxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(5-메틸-푸란-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-methyl-furan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one ;

5-{4-[(비사이클로[2.2.1]헵트-5-엔-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(Bicyclo [2.2.1] hept-5-en-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

N-(4-플루오로-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (4-Fluoro-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide;

5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-{4-[(6-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(6-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-{4-[(5-메탄설포닐-피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(5-methanesulfonyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

5-[4-(2-메탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-피리미딘-2-일-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-pyrimidin-2-yl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

5-{4-[2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

5-{4-[2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one;

N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl) -methanesulfonamide;

5-{4-[(1-메탄설포닐-피롤리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-Methanesulfonyl-pyrrolidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

5-[4-(2-하이드록시-인단-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-hydroxy-indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

5-{4-[(1-하이드록시-사이클로펜틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[2-하이드록시-2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온; 및5- {4- [2-hydroxy-2- (1-methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1 , 3-dihydro-indol-2-one; And

N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드.N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide.

본 발명의 일부의 특정한 구체예로는 이하의 화합물들이 포함된다:Some specific embodiments of the present invention include the following compounds:

N-메틸-N-{3-[({메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노})-메틸]-페닐}-메탄설폰아미드;N-methyl-N- {3-[({methyl- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino})-methyl] -phenyl} -methanesulfonamide;

N-메틸-N-{4-메틸-3-[({메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]아미노})-메틸]-페닐}-메탄설폰아미드;N-methyl-N- {4-methyl-3-[({methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl- Pyrimidin-4-yl] amino})-methyl] -phenyl} -methanesulfonamide;

N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

N-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (2-Methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

5-[4-(3-메탄설포닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

N-메틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

N-(3-메탄설포닐아미노아미노-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (3-methanesulfonylaminoamino-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

N-메틸-N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-Methyl-N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -methyl} -phenyl) -methanesulfonamide;

N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

N-메틸-N-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-Methyl-N- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

5-{4-[((1S,2R)-2-하이드록시-사이클로헥실메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[((1S, 2R) -2-hydroxy-cyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one;

5-[4-((1R,2S)-2-하이드록시-인단-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((1R, 2S) -2-hydroxy-indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole- 2-one;

5-[4-((S)-1-하이드록시메틸-2-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((S) -1-hydroxymethyl-2-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2 -On;

N-(3-메탄설포닐-메틸-아미노)-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (3-methanesulfonyl-methyl-amino) -5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyri Midin-4-ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide;

5-{4-[(1-하이드록시-사이클로펜틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide;

N-(3-플루오로-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (3-fluoro-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide;

5-{4-[2-((S)-1-메탄설포닐-피롤리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2-((S) -1-Methanesulfonyl-pyrrolidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one;

5-{4-[(1-하이드록시-사이클로부틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-hydroxy-cyclobutylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one;

5-{4-[2-((R)-1-메탄설포닐-피롤리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2-((R) -1-methanesulfonyl-pyrrolidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one;

N-(2-플루오로-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (2-Fluoro-6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide;

N-(4-플루오로-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (4-fluoro-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide;

N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide;

N-{2,2-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-N-메틸-메탄설폰아미드;N- {2,2-dimethyl-3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -N-methyl-methanesulfonamide;

N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide;

N-(2,4-디플루오로-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (2,4-difluoro-6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide;

5-[4-((R)-1-메탄설포닐-피페리딘-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((R) -1-methanesulfonyl-piperidin-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole 2-one;

N-메틸-N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide;

5-[4-(1-메탄설포닐-피페리딘-4-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1-Methanesulfonyl-piperidin-4-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one ;

5-{4-[메틸-((R)-1-페닐-에틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [Methyl-((R) -1-phenyl-ethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On;

5-(4-벤질아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-benzylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

N-(4,6-디메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-N-메틸-메탄설폰아미드;N- (4,6-dimethyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amino] -methyl} -pyridin-2-yl) -N-methyl-methanesulfonamide;

5-(4-tert-부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-tert-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one;

5-[4-((1R,5S,6S)-3-메탄설포닐-3-아자-비사이클로[3.1.0]헥스-6-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((1R, 5S, 6S) -3-methanesulfonyl-3-aza-bicyclo [3.1.0] hex-6-ylamino) -5-trifluoromethyl-pyrimidine-2 -Ylamino] -1,3-dihydro-indol-2-one;

N-메틸-N-{3-메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-부틸}-메탄설폰아미드;N-Methyl-N- {3-methyl-3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -butyl} -methanesulfonamide;

N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N- (6-Methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide;

5-{4-[(2-메탄설포닐-피리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-methanesulfonyl-pyridin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On;

2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 아미드;2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid amide;

N-(3-{메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노}-프로필)-메탄설폰아미드;N- (3- {methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -amino} -Propyl) -methanesulfonamide;

N-(2-{메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노}-에틸)-메탄설폰아미드;N- (2- {methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -amino} -Ethyl) -methanesulfonamide;

5-[4-(2-메탄설포닐메틸-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one;

2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 디메틸아미드;2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid dimethylamide;

N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrazin-2-yl) -methanesulfonamide;

에탄설폰산 메틸-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Methyl ethanesulfonic acid- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -phenyl) -amide;

에탄설폰산 (2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -Phenyl) -amide;

N-에틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-ethyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide;

N-{1,1-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N- {1,1-dimethyl-3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide;

N-(5,6-디메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-N-메틸-메탄설폰아미드;N- (5,6-dimethyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amino] -methyl} -pyrazin-2-yl) -N-methyl-methanesulfonamide;

5-{4-[((R)-4-메탄설포닐-모르폴린-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[((R) -4-methanesulfonyl-morpholin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones;

프로판-1-설폰산 (2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Propane-1-sulfonic acid (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -amide;

5-{4-[2-((R)-4-메탄설포닐-모르폴린-3-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2-((R) -4-methanesulfonyl-morpholin-3-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indol-2-one;

에탄설폰산 메틸-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-아미드;Methyl ethanesulfonic acid- (3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -pyridin-2-yl) -amide;

트리플루오로-N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;Trifluoro-N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Ylamino] -propyl} -methanesulfonamide;

사이클로프로판설폰산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;Cyclopropanesulfonic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -amide;

N-에틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-ethyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide;

에탄설폰산 메틸-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Methane-ethanesulfonic acid- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide;

에탄설폰산 에틸-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid ethyl- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -phenyl) -amide;

에탄설폰산 에틸-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid ethyl- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide;

N-에틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-ethyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide;

에탄설폰산 (5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -amide;

에탄설폰산 (3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -amide;

에탄설폰산 메틸-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Methyl ethanesulfonic acid- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide;

2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 메틸아미드;2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid methylamide;

에탄설폰산 {3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;Ethanesulfonic acid {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl}- amides;

C-메탄설포닐-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;C-methanesulfonyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide;

에탄설폰산 {2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드;Ethanesulfonic acid {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl}- amides;

C-메탄설포닐-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;C-methanesulfonyl-N- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -methanesulfonamide;

N-메틸-N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

5-(4-{[1-(2,2,2-트리플루오로-아세틸)-피페리딘-3-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-{[1- (2,2,2-Trifluoro-acetyl) -piperidin-3-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino ) -1,3-dihydro-indol-2-one;

2,2,2-트리플루오로-에탄설폰산 {3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;2,2,2-trifluoro-ethanesulfonic acid {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine -4-ylamino] -propyl} -amide;

N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-2-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-2-yl) -methanesulfonamide;

N-사이클로프로필-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-cyclopropyl-N- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide;

N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrazin-2-yl) -methanesulfonamide;

N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-4-일)-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-4-yl) -methanesulfonamide;

N-사이클로프로필-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-cyclopropyl-N- (3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide;

5-{4-[(2-메탄설포닐메틸-피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-Methanesulfonylmethyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one;

N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(3-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (3-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (5-methyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(4-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (4-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(2-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (2-methyl-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(6-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (6-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(3-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (3-methyl-4-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-2-yl) -methanesulfonamide;

N-메틸-N-(6-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (6-methyl-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(6-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (6-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(2-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-4-일)-메탄설폰아미드;N-Methyl-N- (2-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-4-yl) -methanesulfonamide;

N-메틸-N-(6-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-4-일)-메탄설폰아미드;N-methyl-N- (5-methyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-4-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(6-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-2-yl) -methanesulfonamide;

N-메틸-N-(2-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (2-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(6-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide;

N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-5-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-5-yl) -methanesulfonamide;

N-메틸-N-(2-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (2-methyl-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide;

N-메틸-N-(4-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-5-일)-메탄설폰아미드;N-Methyl-N- (4-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-5-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide;

N-메틸-N-(5-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-methyl-N- (5-methyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide;

N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-5-일)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-5-yl) -methanesulfonamide;

N-메틸-N-(3-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드; 및N-Methyl-N- (3-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide; And

N-메틸-N-(6-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드.N-methyl-N- (6-methyl-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide.

본 발명은 또한, 포유동물에게 비정상적인 세포성장을 치료하는데 효과적인 양의 상기 정의한 바와 같은 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물 또는 프로드럭을 투여하는 것을 포함하는, 인간을 포함하는 포유동물에게서 비정상적인 세포성장을 치료하는 방법에 관한 것이다. 이 방법의 한가지 구체예에서, 비정상적인 세포성장은 폐암, 골암, 췌장암, 피부암, 두경부암, 피부 또는 안내 흑색종, 자궁암, 난소암, 직장암, 항문 부위의 암, 위암, 결장암, 유방 암, 자궁암, 난관암, 자궁내막암, 경부암, 질암, 외음부암, 호지킨병 (Hodgkin's disease), 식도암, 소장암, 내분비계의 암, 갑상선암, 부갑상선암, 부신암, 연조직의 육종, 요도암, 음경암, 전립선암, 만성 또는 급성 백혈병, 림프구성 림프종, 방광암, 신장 또는 요관의 암, 신세포암, 신우암, 중추신경계 (CNS)의 신생물, 원발성 CNS 림프종, 척수축 종양, 뇌간 신경교종, 뇌하수체 선종, 또는 전술한 암 중의 하나 또는 그 이상의 조합을 포함하는 암이나, 이들로 제한되지는 않는다. 한가지 구체예에서, 이 방법은 포유동물에게 상기 암 고형 종양을 치료하는데 효과적인 양의 화학식 1의 화합물을 투여하는 것으로 이루어진다. 한가지 바람직한 구체예에서, 고형 종양은 유방, 폐, 결장, 뇌, 전립선, 위, 췌장, 난소, 피부 (흑색종), 내분비계, 자궁, 고환 및 방광암이다. 상기 방법의 또 다른 구체예에서, 비정상적인 세포성장은 건선, 양성 전립선 비대증 또는 재발협착증을 포함하는 (단, 이들로 제한되지는 않는다) 양성 증식성 질환이다.The invention also encompasses humans, comprising administering to a mammal an amount of a compound of Formula 1 as defined above, or a pharmaceutically acceptable salt, solvate or prodrug thereof, effective to treat abnormal cell growth. To a method for treating abnormal cell growth in a mammal. In one embodiment of this method, the abnormal cell growth is lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, skin or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, anal cancer, gastric cancer, colon cancer, breast cancer, uterine cancer, Fallopian tube cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, Prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvis, neoplasm of central nervous system (CNS), primary CNS lymphoma, spinal contraction tumor, brain stem glioma, pituitary adenoma, Or a cancer comprising one or more combinations of the above-described cancers, but not limited thereto. In one embodiment, the method consists of administering to the mammal an amount of the compound of formula 1 effective to treat the cancer solid tumor. In one preferred embodiment, the solid tumor is breast, lung, colon, brain, prostate, stomach, pancreas, ovary, skin (melanoma), endocrine system, uterus, testes and bladder cancer. In another embodiment of the method, the abnormal cell growth is a benign proliferative disease, including but not limited to psoriasis, benign prostatic hyperplasia or restenosis.

본 발명은 또한, 포유동물에게 비정상적인 세포성장을 치료하는데 효과적인 양의 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물 또는 프로드럭을 유사분열 억제제, 알킬화제, 항대사물질, 삽입성 항생제, 성장인자 억제제, 세포주기 억제제, 효소, 토포이소머라제 억제제, 생물학적 반응 변형제, 항체, 세포독성제, 항호르몬제 및 항안드로겐제로 구성된 군으로부터 선택된 항종양제와 함께 투여하는 것을 포함하는, 포유동물에게서 비정상적인 세포성장을 치료하는 방법에 관한 것이다.The present invention also provides an amount of a compound of Formula 1, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, effective in treating abnormal cell growth in a mammal, including mitosis inhibitors, alkylating agents, anti-metabolic agents, intercalating antibiotics. Administering with an anti-tumor agent selected from the group consisting of growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxic agents, antihormones and antiandrogens, A method of treating abnormal cell growth in a mammal.

본 발명은 또한, 비정상적인 세포성장을 치료하는데 효과적인 양의 상기 정 의한 바와 같은 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물 또는 프로드럭, 및 약제학적으로 허용되는 담체를 포함하는, 인간을 포함한 포유동물에서 비정상적인 세포성장을 치료하기 위한 약제학적 조성물에 관한 것이다. 상기 조성물의 한가지 구체예에서, 비정상적인 세포성장은 폐암, 골암, 췌장암, 피부암, 두경부암, 피부 또는 안내 흑색종, 자궁암, 난소암, 직장암, 항문 부위의 암, 위암, 결장암, 유방암, 자궁암, 난관암, 자궁내막암, 경부암, 질암, 외음부암, 호지킨병, 식도암, 소장암, 내분비계의 암, 갑상선암, 부갑상선암, 부신암, 연조직의 육종, 요도암, 음경암, 전립선암, 만성 또는 급성 백혈병, 림프구성 림프종, 방광암, 신장 또는 요관의 암, 신세포암, 신우암, 중추신경계 (CNS)의 신생물, 원발성 CNS 림프종, 척수축 종양, 뇌간 신경교종, 뇌하수체 선종, 또는 전술한 암 중의 하나 또는 그 이상의 조합을 포함하는 암이나, 이들로 제한되지는 않는다. 상기 약제학적 조성물의 또 다른 구체예에서, 비정상적인 세포성장은 건선, 양성 전립선 비대증 또는 재발협착증을 포함하는 (단, 이들로 제한되지는 않는다) 양성 증식성 질환이다.The present invention also includes a compound of formula 1 as defined above, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and a pharmaceutically acceptable carrier, in an amount effective to treat abnormal cell growth. A pharmaceutical composition for treating abnormal cell growth in a mammal, including humans. In one embodiment of the composition, abnormal cell growth is lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, skin or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal area, gastric cancer, colon cancer, breast cancer, uterine cancer, fallopian tubes Cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, Hodgkin's disease, esophageal cancer, small intestine cancer, cancer of the endocrine system, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penis cancer, prostate cancer, chronic or Acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, neoplasia, central nervous system (CNS) neoplasm, primary CNS lymphoma, spinal contraction tumor, brain stem glioma, pituitary adenoma, or any of the cancers described above Cancers including, but not limited to, one or more combinations. In another embodiment of the pharmaceutical composition, the abnormal cell growth is a benign proliferative disease, including but not limited to psoriasis, benign prostatic hyperplasia or restenosis.

본 발명은 또한, 포유동물에게 비정상적인 세포성장을 치료하는데 효과적인 양의 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물 또는 프로드럭을 유사분열 억제제, 알킬화제, 항대사물질, 삽입성 항생제, 성장인자 억제제, 세포주기 억제제, 효소, 토포이소머라제 억제제, 생물학적 반응 변형제, 항체, 세포독성제, 항호르몬제 및 항안드로겐제로 구성된 군으로부터 선택된 또 다른 항종양제와 함께 투여하는 것을 포함하는, 포유동물에게서 비정상적인 세포성장을 치 료하는 방법에 관한 것이다. 본 발명은 또한, 비정상적인 세포성장을 치료하는데 효과적인 양의 상기 정의한 바와 같은 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물 또는 프로드럭, 및 유사분열 억제제, 알킬화제, 항대사물질, 삽입성 항생제, 성장인자 억제제, 세포주기 억제제, 효소, 토포이소머라제 억제제, 생물학적 반응 변형제, 항체, 세포독성제, 항호르몬제 및 항안드로겐제로 구성된 군으로부터 선택된 또 다른 항종양제를 포함하는, 비정상적인 세포성장 치료용 약제학적 조성물을 제공한다.The present invention also provides an amount of a compound of Formula 1, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, effective in treating abnormal cell growth in a mammal, including mitosis inhibitors, alkylating agents, anti-metabolic agents, intercalating antibiotics. Administering with another anti-tumor agent selected from the group consisting of growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxic agents, anti-hormonal agents and anti-androgens The present invention relates to a method for treating abnormal cell growth in a mammal. The invention also provides an effective amount of a compound of formula (1) as defined above, or a pharmaceutically acceptable salt, solvate or prodrug, and mitosis inhibitors, alkylating agents, anti-metabolites, insertions, in an amount effective to treat abnormal cell growth. Comprising another anti-tumor agent selected from the group consisting of sex antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxic agents, antihormones and antiandrogens, Provided is a pharmaceutical composition for treating abnormal cell growth.

본 발명은 또한, 포유동물에게 하나 또는 그 이상의 상기 열거된 항종양제와 함께, 혈관형성과 연관된 질환을 치료하는데 효과적인 양의 상기 정의한 바와 같은 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물 또는 프로드럭을 투여하는 것을 포함하는, 인간을 포함하는 포유동물에게서 혈관형성과 연관된 질환을 치료하는 방법에 관한 것이다. 이러한 질환에는 흑색종과 같은 암성 종양; 노화-관련된 황반변성, 추정상의 안구 히스토플라즈마증 증후군 (presumed ocular histoplasmosis syndrome), 및 증식성 당뇨병성 망막증으로 인한 망막 혈관신생과 같은 안과 질환; 골다공증, 파제트병 (Paget's disease), 임신의 체액성 고칼슘혈증, 뼈로 전이된 종양으로 인한 고칼슘혈증, 및 글루코코르티코이드 치료에 의해서 유도된 골다공증과 같은 골감소 질환; 관상 재발협착증; 및 아데노바이러스 (adenovirus), 한타바이러스 (hantavirus), 보렐리아 버지도르페리 (Borrelia burgdorferi), 예르시니아 종 (Yersinia spp.), 보르데텔라 퍼튜시스 (Bordetella pertussis) 및 그룹 A 스트렙토코커스 (Streptococcus)로부터 선택된 미생물 병원 체와 연관된 감염을 포함하는 특정의 미생물 감염이 포함된다.The invention also provides an effective amount of a compound of Formula 1 as defined above, or a pharmaceutically acceptable salt thereof, to a mammal in combination with one or more of the antitumor agents listed above, in an amount effective for treating a disease associated with angiogenesis, A method of treating a disease associated with angiogenesis in a mammal, including human, comprising administering a solvate or prodrug. Such diseases include cancerous tumors such as melanoma; Eye diseases such as age-related macular degeneration, presumed ocular histoplasmosis syndrome, and retinal neovascularization due to proliferative diabetic retinopathy; Osteopenia diseases such as osteoporosis, Paget's disease, humoral hypercalcemia of pregnancy, hypercalcemia due to tumors metastasizing to bone, and osteoporosis induced by glucocorticoid treatment; Coronary restenosis; And adenoviruses, hantaviruses, Borrelia borrelia burgdorferi ), Yersinia spp ., Bordetella pertussis), and A is a group containing a specific microbial infection comprises an infection associated with a microbial pathogen selected from Streptococcus (Streptococcus).

본 발명은 또한, 함께 비정상적인 세포성장을 치료하는데 유효한 양의 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물 또는 프로드럭을 그러한 양의 항혈관형성제, 신호전달 억제제 (signal transduction inhibitor), 및 항증식제로부터 선택된 하나 또는 그 이상의 성분을 포함하여, 포유동물에서 비정상적인 세포성장을 치료하는 방법 (및 치료하기 위한 약제학적 조성물)에 관한 것이다.The present invention also provides an amount of a compound of Formula 1, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, effective together to treat abnormal cell growth, with an amount of such an angiogenesis agent, a signal transduction inhibitor. , And one or more components selected from antiproliferative agents, and methods (and pharmaceutical compositions for treating) abnormal cell growth in a mammal.

MMP-2 (매트릭스-메탈로프로테이나제 2) 억제제, MMP-9 (매트릭스-메탈로프로테이나제 9) 억제제 및 COX-II (사이클로옥시게나제 II) 억제제와 같은 항혈관형성제가 본 명세서에 기술된 방법 및 약제학적 조성물에서 화학식 1의 화합물과 함께 사용될 수 있다. 유용한 COX-II 억제제의 예로는 셀레브렉스 (CELEBREX™)(셀레콕시브), 벡스트라 (Bextra)(발데콕시브), 파라콕시브, 비옥스 (Vioxx)(로페콕시브), 및 아르콕시아 (Arcoxia)(에토리콕시브)가 포함된다. 유용한 매트릭스 메탈로프로테이나제 억제제의 예는 WO 96/33172 (1996년 10월 24일 공개됨), WO 96/27583 (1996년 3월 7일 공개됨), 유럽특허출원 제 97304971.1 호 (1997년 7월 8일 출원됨), 유럽특허출원 제 99308617.2 호 (1999년 10월 29일 출원됨), WO 98/07697 (1998년 2월 26일 공개됨), WO 98/03561 (1998년 1월 29일 공개됨), WO 98/34918 (1998년 8월 13일 공개됨), WO 98/34915 (1998년 8월 13일 공개됨), WO 98/33768 (1998년 8월 6일 공개됨), WO 98/30566 (1998년 7월 16일 공개됨), 유럽특허공보 제 606,046 호 (1994년 7월 13일 공고됨), 유럽특허공보 제 931,788 호 (1999년 7월 28일 공고됨), WO 90/05719 (1990년 5월 31일 공개됨), WO 99/52910 (1999년 10월 21일 공개됨), WO 99/52889 (1999년 10월 21일 공개됨), WO 99/29667 (1999년 6월 17일 공개됨), PCT 국제출원 PCT/IB98/01113 (1998년 7월 21일 출원됨), 유럽특허출원 제 99302232.1 호 (1999년 3월 25일 출원됨), 영국특허출원 제 9912961.1 호 (1999년 6월 3일 출원됨), 미국 가특허출원 제 60/148,464 호 (1999년 8월 12일 출원됨), 미국특허 제 5,863,949 호 (1999년 1월 26일 허여됨), 미국특허 제 5,861,510 호 (1999년 1월 19일 허여됨), 및 유럽특허공보 제 780,386 호 (1997년 6월 25일 공고됨)(이들은 모두 본 명세서에 온전히 참고로 포함되어 있다)에 기술되어 있다. 바람직한 MMP-2 및 MMP-9 억제제는 MMP-1을 억제하는 활성을 거의 또는 전혀 갖지 않는 것이다. 더욱 바람직한 것은 다른 매트릭스-메탈로프로테이나제 (즉 MMP-1, MMP-3, MMP-4, MMP-5, MMP-6, MMP-7, MMP-8, MMP-10, MMP-11, MMP-12 및 MMP-13)에 비해서 MMP-2 및/또는 MMP-9를 선택적으로 억제하는 것이다.Antiangiogenic agents such as MMP-2 (matrix-metalloproteinase 2) inhibitors, MMP-9 (matrix-metalloproteinase 9) inhibitors and COX-II (cyclooxygenase II) inhibitors are described herein. It can be used with the compound of formula 1 in the methods and pharmaceutical compositions described. Examples of useful COX-II inhibitors include CELEBREX ™ (Celecoxib), Bextra (Valdecoxib), Paracoxib, Viox (Ropecoxib), and Arcoxia. (Ethoxycoxib) is included. Examples of useful matrix metalloproteinase inhibitors are WO 96/33172 (published October 24, 1996), WO 96/27583 (published March 7, 1996), European Patent Application No. 97304971.1 (July 1997). Filed 8), European Patent Application No. 99308617.2 (filed October 29, 1999), WO 98/07697 (published February 26, 1998), WO 98/03561 (published January 29, 1998) WO 98/34918 published 13 August 1998 WO 98/34915 published 13 August 1998 WO 98/33768 published 6 August 1998 WO 98/30566 1998 Published July 16), European Patent Publication No. 606,046 (published July 13, 1994), European Patent Publication No. 931,788 (published July 28, 1999), WO 90/05719 (May 1990) Published 31), WO 99/52910 (published October 21, 1999), WO 99/52889 (published October 21, 1999), WO 99/29667 (published June 17, 1999), PCT International Application PCT / IB98 / 01113 (filed July 21, 1998), European Patent Application No. 99302232.1 (published March 25, 1999) US Patent Application No. 9912961.1 (filed June 3, 1999), US Provisional Patent Application No. 60 / 148,464 (filed August 12, 1999), US Patent No. 5,863,949 (January 1999) 26, US Patent No. 5,861,510, issued January 19, 1999, and European Patent Publication No. 780,386, issued June 25, 1997, all of which are incorporated herein by reference in their entirety. In the Preferred MMP-2 and MMP-9 inhibitors are those having little or no activity inhibiting MMP-1. More preferred are other matrix-metalloproteinases (ie MMP-1, MMP-3, MMP-4, MMP-5, MMP-6, MMP-7, MMP-8, MMP-10, MMP-11, MMP -12 and MMP-13) selectively inhibits MMP-2 and / or MMP-9.

본 발명의 화합물과 함께 사용하는데 유용한 MMP 억제제의 일부 구체적인 예는 AG-3340, RO 32-3555, RS 13-0830, 및 이하의 리스트에 열거된 화합물이다:Some specific examples of MMP inhibitors useful for use with the compounds of the present invention are AG-3340, RO 32-3555, RS 13-0830, and the compounds listed in the following list:

3-[[4-(4-플루오로-페녹시)-벤젠설포닐]-(1-하이드록시카바모일-사이클로펜틸)-아미노]-프로피온산;3-[[4- (4-Fluoro-phenoxy) -benzenesulfonyl]-(1-hydroxycarbamoyl-cyclopentyl) -amino] -propionic acid;

3-엑소-3-[4-(4-플루오로-페녹시)-벤젠설포닐아미노]-8-옥사-비사이클로[3.2.1]옥탄-3-피페리딘-2-카복실산 하이드록시아미드;3-exo-3- [4- (4-fluoro-phenoxy) -benzenesulfonylamino] -8-oxa-bicyclo [3.2.1] octane-3-piperidine-2-carboxylic acid hydroxyamide ;

(2R,3R) 1-[4-(2-클로로-4-플루오로-벤질옥시)-벤젠설포닐]-3-하이드록시-3-메틸-피페리딘-2-카복실산 하이드록시아미드;(2R, 3R) 1- [4- (2-Chloro-4-fluoro-benzyloxy) -benzenesulfonyl] -3-hydroxy-3-methyl-piperidine-2-carboxylic acid hydroxyamide;

4-[4-(4-플루오로-페녹시)-벤젠설포닐아미노]-테트라하이드로-피란-4-카복실산 하이드록시아미드;4- [4- (4-Fluoro-phenoxy) -benzenesulfonylamino] -tetrahydro-pyran-4-carboxylic acid hydroxyamide;

3-[[4-(4-플루오로-페녹시)-벤젠설포닐]-(1-하이드록시카바모일-사이클로부틸)-아미노]-프로피온산;3-[[4- (4-Fluoro-phenoxy) -benzenesulfonyl]-(1-hydroxycarbamoyl-cyclobutyl) -amino] -propionic acid;

4-[4-(4-클로로-페녹시)-벤젠설포닐아미노]-테트라하이드로-피란-4-카복실산 하이드록시아미드;4- [4- (4-Chloro-phenoxy) -benzenesulfonylamino] -tetrahydro-pyran-4-carboxylic acid hydroxyamide;

3-[4-(4-클로로-페녹시)-벤젠설포닐아미노]-테트라하이드로-피란-3-카복실산 하이드록시아미드;3- [4- (4-Chloro-phenoxy) -benzenesulfonylamino] -tetrahydro-pyran-3-carboxylic acid hydroxyamide;

(2R,3R) 1-[4-(4-플루오로-2-메틸-벤질옥시)-벤젠설포닐]-3-하이드록시-3-메틸-피페리딘-2-카복실산 하이드록시아미드;(2R, 3R) 1- [4- (4-Fluoro-2-methyl-benzyloxy) -benzenesulfonyl] -3-hydroxy-3-methyl-piperidine-2-carboxylic acid hydroxyamide;

3-[[4-(4-플루오로-페녹시)-벤젠설포닐]-(1-하이드록시카바모일-1-메틸-에틸)-아미노]-프로피온산;3-[[4- (4-Fluoro-phenoxy) -benzenesulfonyl]-(1-hydroxycarbamoyl-1-methyl-ethyl) -amino] -propionic acid;

3-[[4-(4-플루오로-페녹시)-벤젠설포닐]-(4-하이드록시카바모일-테트라하이드로-피란-4-일)-아미노]-프로피온산;3-[[4- (4-Fluoro-phenoxy) -benzenesulfonyl]-(4-hydroxycarbamoyl-tetrahydro-pyran-4-yl) -amino] -propionic acid;

3-엑소-3-[4-(4-클로로-페녹시)-벤젠설포닐아미노]-8-옥사-비사이클로[3.2.1]옥탄-3-카복실산 하이드록시아미드;3-exo-3- [4- (4-chloro-phenoxy) -benzenesulfonylamino] -8-oxa-bicyclo [3.2.1] octane-3-carboxylic acid hydroxyamide;

3-엔도-3-[4-(4-플루오로-페녹시)-벤젠설포닐아미노]-8-옥사-비사이클로[3.2.1]옥탄-3-카복실산 하이드록시아미드; 및3-endo-3- [4- (4-fluoro-phenoxy) -benzenesulfonylamino] -8-oxa-bicyclo [3.2.1] octane-3-carboxylic acid hydroxyamide; And

3-[4-(4-플루오로-페녹시)-벤젠설포닐아미노]-테트라하이드로-피란-3-카복실산 하이드록시아미드; 및3- [4- (4-Fluoro-phenoxy) -benzenesulfonylamino] -tetrahydro-pyran-3-carboxylic acid hydroxyamide; And

상기 화합물의 약제학적으로 허용되는 염, 용매화물 및 프로드럭.Pharmaceutically acceptable salts, solvates and prodrugs of the compounds.

VEGF 억제제, 예를 들어, SU-11248, SU-5416 및 SU-6668 (Sugen Inc. of South San Francisco, California, USA)도 또한 화학식 1의 화합물과 배합될 수 있다. VEGF 억제제는 예를 들어, WO 99/24440 (1999년 5월 20일 공개됨), PCT 국제출원 PCT/IB99/00797 (1999년 5월 3일 출원됨), WO 95/21613 (1995년 8월 17일 공개됨), WO 99/61422 (1999년 12월 2일 공개됨), 미국특허 제 5,834,504 호 (1998년 11월 10일 허여됨), WO 98/50356 (1998년 11월 12일 공개됨), 미국특허 제 5,883,113 호 (1999년 3월 16일 허여됨), 미국특허 제 5,886,020 호 (1999년 3월 23일 허여됨), 미국특허 제 5,792,783 호 (1998년 8월 11일 허여됨), 미국특허 제 US 6,653,308 호 (2003년 11월 25일 허여됨), WO 99/10349 (1999년 3월 4일 공개됨), WO 97/32856 (1997년 9월 12일 공개됨), WO 97/22596 (1997년 6월 26일 공개됨), WO 98/54093 (1998년 12월 3일 공개됨), WO 98/02438 (1998년 1월 22일 공개됨), WO 99/16755 (1999년 4월 8일 공개됨), 및 WO 98/02437 (1998년 1월 22일 공개됨)(이들은 모두 본 명세서에 온전히 참고로 포함되어 있다)에 기술되어 있다. 일부의 특정한 VEGF 억제제의 그 밖의 다른 예는 IM862 (Cytran Inc. of Kirkland, Washington, USA); 제넨텍 인코포레이티드 (Genentech, Inc. of South San Francisco, California)의 항-VEGF 모노클로날 항체인 아바스틴 (Avastin); 및 리보자임 (Ribozyme, Boulder, Colorado) 및 치론 (Chiron, Emeryville, California)으로부터의 합성 리보자임인 앤지오자임 (angiozyme)이다.VEGF inhibitors such as SU-11248, SU-5416 and SU-6668 (Sugen Inc. of South San Francisco, California, USA) may also be combined with a compound of Formula 1. VEGF inhibitors are described, for example, in WO 99/24440 (published May 20, 1999), PCT International Application PCT / IB99 / 00797 (filed May 3, 1999), WO 95/21613 (August 17, 1995). Published), WO 99/61422 (published 2 December 1999), US Pat. No. 5,834,504, issued Nov. 10, 1998, WO 98/50356 (published November 12, 1998), US Pat. 5,883,113, issued March 16, 1999, US Patent 5,886,020, issued March 23, 1999, US Patent 5,792,783, issued August 11, 1998, US Patent US 6,653,308, issued November 25, 2003, WO 99/10349, published March 4, 1999, WO 97/32856, published September 12, 1997, WO 97/22596, June 1997 Published 26), WO 98/54093 (published 3 December 1998), WO 98/02438 (published January 22, 1998), WO 99/16755 (published April 8, 1999), and WO 98 / 02437 (published January 22, 1998), all of which are incorporated herein by reference in their entirety. Other examples of some specific VEGF inhibitors are IM862 (Cytran Inc. of Kirkland, Washington, USA); Avastin, an anti-VEGF monoclonal antibody from Genentech, Inc. of South San Francisco, California; And angiozyme, a synthetic ribozyme from Ribozyme (Ribozyme, Boulder, Colorado) and Chiron (Emeryville, California).

GW-282974 (Glaxo Wellcome plc), 및 모노클로날 항체 AR-209 (Aronex Pharmaceuticals Inc. of The Woodlands, Texas, USA) 및 2B-1 (Chiron)과 같은 erbB2 수용체 억제제를 화학식 1의 화합물과 배합하여 투여할 수도 있다. 이러한 erbB2 억제제에는 헤르셉틴 (Herceptin), 2C4 및 퍼투주마브 (pertuzumab)가 포함된다. 이러한 erbB2 억제제는 WO 98/02434 (1998년 1월 22일 공개됨), WO 99/35146 (1999년 7월 15일 공개됨), WO 99/35132 (1999년 7월 15일 공개됨), WO 98/02437 (1998년 1월 22일 공개됨), WO 97/13760 (19979년 4월 17일 공개됨), WO 95/19970 (1995년 7월 27일 공개됨), 미국특허 제 5,587,458 호 (1996년 12월 24일 허여됨), 및 미국특허 제 5,877,305 호 (1999년 3월 2일 허여됨)(이들은 각각 본 명세서에 온전히 참고로 포함되어 있다)에 기술된 것을 포함한다. 본 발명에서 유용한 erbB2 수용체 억제제는 또한 미국 가특허출원 제 60/117,341 호 (1999년 1월 27일 출원됨), 및 미국 가특허출원 제 60/117,346 호 (1999년 1월 27일 출원됨)(이들은 둘 다 본 명세서에 온전히 참고로 포함되어 있다)에 기술되어 있다. 그 밖의 다른 erbB2 수용체 억제제에는 TAK-165 (Takeda) 및 GW-572016 (Glaxo-Wellcome)이 포함된다.ErbB2 receptor inhibitors such as GW-282974 (Glaxo Wellcome plc), and the monoclonal antibody AR-209 (Aronex Pharmaceuticals Inc. of The Woodlands, Texas, USA) and 2B-1 (Chiron) It may also be administered. Such erbB2 inhibitors include Herceptin, 2C4 and pertuzumab. Such erbB2 inhibitors include WO 98/02434 (published January 22, 1998), WO 99/35146 (published July 15, 1999), WO 99/35132 (published July 15, 1999), WO 98/02437 (Published January 22, 1998), WO 97/13760 (published April 17, 19979), WO 95/19970 (published July 27, 1995), US Pat. No. 5,587,458 (December 24, 1996) Issued), and US Pat. No. 5,877,305, issued March 2, 1999, each of which is incorporated herein by reference in its entirety. ErbB2 receptor inhibitors useful in the present invention also include U.S. Provisional Patent Application No. 60 / 117,341 (filed Jan. 27, 1999), and U.S. Provisional Patent Application No. 60 / 117,346 (filed January 27, 1999) ( Both of which are incorporated herein by reference in their entirety. Other erbB2 receptor inhibitors include TAK-165 (Takeda) and GW-572016 (Glaxo-Wellcome).

스티렌 유도체와 같은 다양한 다른 화합물들도 또한 타이로신 키나제 억제특성을 갖는 것으로 나타났으며, 타이로신 키나제 억제제의 일부는 erbB2 수용체 억제제로서 확인되었다. 더욱 최근에, 유럽특허공보, 즉 EP 0 566 226 A1 (1993년 10월 20일 공고됨), EP 0 602 851 A1 (1994년 6월 22일 공고됨), EP 0 635 507 A1 (1995년 1월 25일 공고됨), EP 0 635 498 A1 (1995년 1월 25일 공고됨), 및 EP 0 520 722 A1 (1992년 12월 30일 공고됨)은 그들의 타이로신 키나제 억제특성으로 인 하여 항암특성을 갖는 것으로 특정의 비사이클릭 유도체, 특히 퀴나졸린 유도체를 언급하였다. 또한, 국제특허출원 WO 92/20642 (1992년 11월 26일 공개됨)는 비정상적인 세포증식을 억제하는데 유용한 타이로신 키나제 억제제로서 특정의 비스-모노 및 비사이클릭 아릴 및 헤테로아릴 화합물을 언급하고 있다. 국제특허출원 WO 96/16960 (1996년 6월 6일 공개됨), WO 96/09294 (1996년 3월 6일 공개됨), WO 97/30034 (1997년 8월 21일 공개됨), WO 98/02434 (1998년 1월 22일 공개됨), WO 98/02437 (1998년 1월 22일 공개됨) 및 WO 98/02438 (1998년 1월 22일 공개됨)도 또한 동일한 목적으로 유용한 타이로신 키나제 억제제로서 치환된 비사이클릭 헤테로방향족 유도체를 언급하였다. 항암 화합물을 언급하고 있는 그 밖의 다른 특허출원은 국제특허출원 WO 00/44728 (2000년 8월 3일 공개됨), EP 1029853A1 (2000년 8월 23일 공개됨), 및 WO 01/98277 (2001년 12월 12일 공개됨)(이들은 모두 본 명세서에 온전히 참고로 포함되어 있다)이다.Various other compounds, such as styrene derivatives, have also been shown to have tyrosine kinase inhibitory properties, and some of the tyrosine kinase inhibitors have been identified as erbB2 receptor inhibitors. More recently, European Patent Publications EP 0 566 226 A1 (published 20 October 1993), EP 0 602 851 A1 (published June 22, 1994), EP 0 635 507 A1 (1995 1). May 25), EP 0 635 498 A1 (announced January 25, 1995), and EP 0 520 722 A1 (announced December 30, 1992) have anticancer properties due to their tyrosine kinase inhibitory properties. Certain acyclic derivatives, especially quinazoline derivatives, are mentioned as having. In addition, International Patent Application WO 92/20642 (published November 26, 1992) mentions certain bis-mono and bicyclic aryl and heteroaryl compounds as tyrosine kinase inhibitors useful for inhibiting abnormal cell proliferation. International patent application WO 96/16960 (published 6 June 1996), WO 96/09294 (published 6 March 1996), WO 97/30034 (published 21 August 1997), WO 98/02434 ( Published January 22, 1998), WO 98/02437 (published January 22, 1998) and WO 98/02438 (published January 22, 1998) are also substituted bisoxy substituted as useful tyrosine kinase inhibitors for the same purpose. Mention is made of click heteroaromatic derivatives. Other patent applications that mention anticancer compounds are described in international patent applications WO 00/44728 published 3 August 2000, EP 1029853A1 published 23 August 2000, and WO 01/98277 12 December 2001. Published May 12), all of which are incorporated herein by reference in their entirety.

본 발명의 화합물과 함께 사용될 수 있는 그 밖의 다른 항증식제에는 미국특허출원 제 09/221946 (1998년 12월 28일 출원됨); 09/454058 (1999년 12월 2일 출원됨); 09/501163 (2000년 2월 9일 출원됨); 09/539930 (2000년 3월 31일 출원됨); 09/202796 (1997년 5월 22일 출원됨); 09/384339 (1999년 8월 26일 출원됨); 및 09/383755 호 (1999년 8월 26일 출원됨)에 기술되고 특허청구된 화합물; 및 미국 가특허출원 60/168207 (1999년 11월 30일 출원됨); 60/170119 (1999년 12월 10일 출원됨); 60/177718 (2000년 1월 21일 출원됨); 60/168217 (1999년 11월 30일 출원됨); 및 60/200834 호 (2000년 5월 1일 출원됨)에 기술되고 특허청구된 화합물을 포함한 효소 파르네실 단백질 트랜스퍼라제의 억제제 및 수용체 타이로신 키나제 PDGFr의 억제제가 포함된다. 전술한 특허출원 및 가특허출원은 각각 본 명세서에 온전히 참고로 포함되어 있다.Other antiproliferative agents that can be used with the compounds of the present invention include US patent application Ser. No. 09/221946, filed Dec. 28, 1998; 09/454058 (filed December 2, 1999); 09/501163 (filed February 9, 2000); 09/539930 (filed March 31, 2000); 09/202796 (filed May 22, 1997); 09/384339 (filed August 26, 1999); And compounds described and claimed in 09/383755 (filed August 26, 1999); And US Provisional Patent Application 60/168207, filed November 30, 1999; 60/170119 (filed December 10, 1999); 60/177718 (filed January 21, 2000); 60/168217 (filed November 30, 1999); And inhibitors of the enzyme farnesyl protein transferase and inhibitors of the receptor tyrosine kinase PDGFr, including compounds described and claimed in 60/200834 (filed May 1, 2000). The foregoing patent applications and provisional patent applications are each incorporated herein by reference in their entirety.

화학식 1의 화합물은 또한, CTLA4 (세포독성 림프구 항원 4) 항체와 같이 항종양 면역반응을 증진시킬 수 있는 약제, 및 CTLA4를 차단할 수 있는 그 밖의 다른 약제; 및 그 밖의 다른 파르네실 단백질 트랜스퍼라제 억제제, 예를 들어, 상기 "발명의 배경"에 인용된 문헌에 기술된 파르네실 단백질 트랜스퍼라제 억제제와 같은 항증식제를 포함하는 비정상적인 세포성장 또는 암을 치료하는데 유용한 그 밖의 다른 약제와 함께 사용될 수도 있다. 본 발명에서 사용될 수 있는 특정의 CTLA4 항체에는 본 명세서에 온전히 참고로 포함되어 있는 미국 가특허출원 제 60/113,647 호 (1998년 12월 23일 출원됨)에 기술된 것이 포함된다.Compounds of Formula 1 may also include agents that can enhance anti-tumor immune responses, such as CTLA4 (cytotoxic lymphocyte antigen 4) antibodies, and other agents that can block CTLA4; And other farnesyl protein transferase inhibitors, such as anti-proliferative agents such as the farnesyl protein transferase inhibitors described in the literature cited above in the "Background of the Invention". It can also be used in conjunction with other useful agents. Certain CTLA4 antibodies that can be used in the present invention include those described in US Provisional Patent Application No. 60 / 113,647, filed December 23, 1998, which is incorporated herein by reference in its entirety.

화학식 1의 화합물은 유일한 치료법으로 사용될 수 있거나, 하나 또는 그 이상의 다른 항종양제, 예를 들어, 유사분열 억제제, 예를 들어, 빈블라스틴; 알킬화제, 예를 들어, 시스플라틴, 옥살리플라틴, 카르보플라틴 및 사이클로포스파마이드; 항대사물질, 예를 들어, 5-플루오로우라실, 카페시타빈, 사이토신 아라비노사이드 및 하이드록시우레아, 또는 예를 들어, N-(5-[N-(3,4-디하이드로-2-메틸-4-옥소퀴나졸린-6-일메틸)-N-메틸아미노]-2-테노일)-L-글루탐산과 같은 유럽특허출원 제 239362 호에 기술된 바람직한 항대사물질 중의 하나; 성장인자 억제제; 세포주기 억제제; 삽입성 항생제, 예를 들어, 아드리아마이신 및 블레오마이신; 효소, 예를 들어, 인터페론; 및 항호르몬제, 예를 들어, 놀바덱스 (Nolvadex; 타목시펜)과 같은 항에스트로겐제, 또는 예를 들어, 카소덱스 (Casodex; (4'-시아노-3-(4-플루오로페닐설포닐)-2-하이드록시-2-메틸-3'-(트리플루오로메틸)프로피온아닐리드)와 같은 항안드로겐제로부터 선택된 항종양제를 포함할 수 있다.The compound of formula 1 may be used as the only treatment or may include one or more other antitumor agents, such as mitosis inhibitors such as vinblastine; Alkylating agents such as cisplatin, oxaliplatin, carboplatin and cyclophosphamide; Antimetabolites, for example 5-fluorouracil, capecitabine, cytosine arabinoside and hydroxyurea, or for example N- (5- [N- (3,4-dihydro-2) One of the preferred anti-metabolites described in European Patent Application No. 239362, such as -methyl-4-oxoquinazolin-6-ylmethyl) -N-methylamino] -2-tenoyl) -L-glutamic acid; Growth factor inhibitors; Cell cycle inhibitors; Intercalating antibiotics such as adriamycin and bleomycin; Enzymes such as interferon; And anti-hormonal agents, for example antiestrogens such as Nolvadex (tamoxifen), or for example, Casodex; (4'-cyano-3- (4-fluorophenylsulfonyl) Anti-androgens such as -2-hydroxy-2-methyl-3 '-(trifluoromethyl) propionanilide).

본 발명의 화합물은 단독으로, 또는 다양한 항암제 또는 보조치료제 중의 하나 또는 그 이상과 함께 사용될 수 있다. 예를 들어, 본 발명의 화합물은 세포독성제, 예를 들어, 캄프토테신, 이리노테칸 HCl (캄프토사르 (Camptosar)), 에도테카린, SU-11248, 에피루비신 (엘렌스 (Ellence)), 도세탁셀 (탁소테레 (Taxotere)), 파클리탁셀, 리툭시마브 (리툭산 (Rituxan)), 베바시주마브 (아바스틴 (Avastin)), 이마티니브 메실레이트 (글리백 (Gleevac)), 에르비툭스 (Erbitux), 게피티니브 (이레사 (Iressa)), 및 이들의 배합물로 구성된 군으로부터 선택된 하나 또는 그 이상과 함께 사용될 수 있다. 본 발명은 또한, 본 발명의 화합물을 호르몬 치료법, 예를 들어, 엑세메스탄 (아로마신 (Aromasin)), 루프론 (Lupron), 아나스트로졸 (아리미덱스 (Arimidex)), 타목시펜 시트레이트 (놀바덱스 (Nolvadex)), 트렐스타 (Trelstar), 및 이들의 배합물과 함께 사용하는데 관한 것이다. 추가로, 본 발명은 단독으로, 또는 하나 또는 그 이상의 보조치료제, 예를 들어, 필그라스팀 (Filgrastim; 노이포젠 (Neupogen)), 온단세트론 (조프란 (Zofran)), 프라그민 (Fragmin), 프로크릿 (Procrit), 알록시 (Aloxi), 에멘드 (Emend), 또는 이들의 배합물과 함께 본 발명의 화합물을 제공한다. 이러한 공동치료는 치료의 각각의 성분을 동시, 연속 또는 별도로 투약하는 방법에 의해서 달성될 수 있다.The compounds of the present invention may be used alone or in combination with one or more of various anticancer or adjuvant therapies. For example, the compounds of the present invention may be cytotoxic agents such as camptothecin, irinotecan HCl (Camptosar), edotecarin, SU-11248, epirubicin (Ellence) , Docetaxel (Taxotere), paclitaxel, rituximab (Rituxan), bevacizumab (Avastin), imatinib mesylate (Gleevac), Erbitux ), Gefitinib (Iressa), and combinations thereof. The present invention also provides a method of treating a compound of the present invention with hormonal therapy such as exemestane (Aromasin), Lupron, anastrozole (Arimidex), tamoxifen citrate (nolvadex). (Nolvadex), Trelstar, and combinations thereof. In addition, the present invention alone or in combination with one or more adjuvant agents such as Filgrastim (Neupogen), ondansetron (Zofran), pragmin, Compounds of the invention are provided together with Procrit, Aloxi, Emend, or combinations thereof. Such co-treatment may be accomplished by methods of administering each component of the treatment simultaneously, sequentially or separately.

본 발명의 화합물은 항종양제, 알킬화제, 항대사물질, 항생제, 식물-유도된 항종양제, 캄프토테신 유도체, 타이로신 키나제 억제제, 항체, 인터페론 및/또는 생물학적 반응 변형제와 함께 사용될 수 있다. 이와 관련하여, 이하에는 본 발명의 화합물과 함께 사용될 수 있는 이차 약제의 예의 비제한적 리스트가 제공된다:The compounds of the present invention can be used with antitumor agents, alkylating agents, antimetabolic agents, antibiotics, plant-derived antitumor agents, camptothecin derivatives, tyrosine kinase inhibitors, antibodies, interferons and / or biological response modifiers. In this regard, the following provides a non-limiting list of examples of secondary agents that can be used with the compounds of the present invention:

● 알킬화제에는 나이트로젠 머스타드 N-옥사이드, 사이클로포스파마이드, 이포스파마이드, 멜파란, 부설판, 마이토브로니톨, 카르보쿠온, 티오테파, 라니무스틴, 니무스틴, 테모졸로마이드, AMD-473, 알트레타민, AP-5280, 아파지쿠온, 브로스탈리신, 벤다무스틴, 카르무스틴, 에스트라무스틴, 포테무스틴, 글루포스파마이드, 이포스파마이드, KW-2170, 마포스파마이드 및 미토락톨이 포함되나, 이들로 제한되지는 않으며; 백금-배위결합된 알킬화 화합물에는 시스플라틴, 카르보플라틴, 엡타플라틴, 로바플라틴, 네다플라틴, 옥살리플라틴 또는 사트르플라틴이 포함되나, 이들로 제한되지는 않는다;Alkylating agents include nitrogen mustard N-oxides, cyclophosphamides, ifosmamides, melfarans, busulfans, mitobronitol, carbocuone, thiotepa, ranimustine, nimustine, temozolomide, AMD- 473, Altretamine, AP-5280, Afajicuon, Brostallycin, Bendamustine, Carmustine, Estramustine, Potemustine, Gluphosphamide, Iphosphamide, KW-2170, Maposphamide And mitolactol, but are not limited to these; Platinum-coordinated alkylated compounds include, but are not limited to, cisplatin, carboplatin, eptaplatin, lovaplatin, nedaplatin, oxaliplatin or satrplatin;

● 항대사물질에는 메토트렉세이트, 6-머캅토퓨린 리보사이드, 머캅토퓨린, 단독으로 또는 로이코보린과 병용하는 5-플루오로우라실 (5-FU), 테가푸르, UFT, 독시플루리딘, 카르모푸르, 사이타라빈, 사이타라빈 옥포스페이트, 에노시타빈, S-1, 젬시타빈, 플루다라빈, 5-아자시티딘, 카페시타빈, 클라드리빈, 클로파라빈, 데시타빈, 에플로르니틴, 에티닐사이티딘, 사이토신 아라비노사이드, 하이드록시우레아, TS-1, 멜파란, 넬라라빈, 놀라트렉시드, 옥포스페이트, 디나트륨 프레메트렉시드, 펜토스타틴, 펠리트렉솔, 랄티트렉시드, 트리아핀, 트리메트렉세이트, 비다라빈, 빈크리스틴, 비노렐빈; 또는 예를 들어, N-(5-[N-(3,4-디하이드로-2-메틸-4-옥 소퀴나졸린-6-일메틸)-N-메틸아미노]-2-테노일)-L-글루탐산과 같은 유럽특허출원 제 239362 호에 기술된 바람직한 항대사물질 중의 하나가 포함되나, 이들로 제한되지는 않는다;Antimetabolic agents include methotrexate, 6-mercaptopurine riboside, mercaptopurine, 5-fluorouracil (5-FU), alone or in combination with leucoborin, tegapur, UFT, doxyfluidine, carr Morphur, cytarabine, cytarabine oxphosphate, enositabine, S-1, gemcitabine, fludarabine, 5-azacytidine, capecitabine, cladribine, cloparabine, decitabine, e Flornitine, ethynylcytidine, cytosine arabinoside, hydroxyurea, TS-1, melfaran, ellarabine, nolatrexside, oxphosphate, disodium premetrexedide, pentostatin, felitrexole, ralti Trexid, triapine, trimetrexate, vidarabine, vincristine, vinorelbine; Or for example N- (5- [N- (3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl) -N-methylamino] -2-tenoyl)- One of the preferred anti-metabolic agents described in European Patent Application No. 239362, such as L-glutamic acid, is included;

● 항생제에는 아클라루비신, 액티노마이신 D, 암루비신, 안나마이신, 블레오마이신, 다우노루비신, 독소루비신, 엘사미트루신, 에피루비신, 갈라루비신, 이다루비신, 마이토마이신 C, 네모루비신, 네오카르지노스타틴, 페플로마이신, 피라루비신, 베레카마이신, 스티말라머, 스트렙토조신, 발루비신 또는 지노스타틴이 포함되나, 이들로 제한되지는 않는다;● Antibiotics include aclarubicin, actinomycin D, amrubicin, annamycin, bleomycin, daunorubicin, doxorubicin, elsamutrucin, epirubicin, galarubicin, idarubicin, mitomycin C, Nemorubicin, neocardinostatin, peplomycin, pyrarubicin, beremycin, stymalamer, streptozosin, valerubicin or ginostatin;

● 호르몬 요법제, 예를 들어, 엑세메스탄 (아로마신 (Aromasin)), 루프론 (Lupron), 아나스트로졸 (아리미덱스 (Arimidex)), 독세르칼시페롤, 파드로졸, 포르메스탄, 타목시펜 시트레이트 (놀바덱스 (Nolvadex)) 및 풀베스트란트와 같은 항에스트로겐제, 트렐스타 (Trelstar), 토레미펜, 랄록시펜, 라소폭시펜, 레트로졸 (페마라 (Femara)), 또는 비칼루타마이드, 플루타마이드, 미페프리스톤, 닐루타마이드, 카소덱스 (Casodex™; (4'-시아노-3-(4-플루오로페닐설포닐)-2-하이드록시-2-메틸-3'-(트리플루오로메틸)프로피온아닐리드)와 같은 항안드로겐제 및 이들의 배합물;Hormonal therapies such as exemestane (Aromasin), Lupron, anastrozole (Arimidex), dosercalciferol, padrosol, formumestan, Antiestrogens, such as tamoxifen citrate (Nolvadex) and fulvestrant, Trelstar, toremifene, raloxifene, lasopoxifen, letrozole (Femara), or bicalutamide , Flutamide, mifepristone, nilutamide, casodex ™; (4'-cyano-3- (4-fluorophenylsulfonyl) -2-hydroxy-2-methyl-3 '-(tri Antiandrogens such as fluoromethyl) propionanilide) and combinations thereof;

● 식물-유도된 항종양제에는 예를 들어, 유사분열 억제제, 예를 들어, 빈블라스틴, 독세탁셀 (탁소테레 (Taxotere)) 및 파클리탁셀로부터 선택된 것이 포함된다;Plant-derived anti-tumor agents include, for example, mitosis inhibitors such as those selected from vinblastine, docetaxel (Taxotere) and paclitaxel;

● 세포독성 토포이소머라제 억제제에는 아클라루비신, 암모나파이드, 벨로 테칸, 캄프토테신, 10-하이드록시캄프토테신, 9-아미노캄프토테신, 디플로모테칸, 이리노테칸 HCl (캄프토사르 (Camptosar)), 에도테카린, 에피루비신 (엘렌스 (Ellence)), 에토포사이드, 엑사테칸, 지마테칸, 루르토테칸, 미톡산트론, 피라루비신, 픽산트론, 루비테칸, 소부족산, SN-38, 타플루포사이드, 및 토포테칸으로 구성된 군으로부터 선택된 하나 또는 그 이상의 약제, 및 이들의 배합물이 포함된다;Cytotoxic topoisomerase inhibitors include aclarubicin, ammonapid, velotecan, camptothecin, 10-hydroxycamptothecin, 9-aminocamptothecin, diplomotecan, irinotecan HCl (campto) Camptosar), Edothecarin, Epirubicin (Ellence), Etoposide, Exatecan, Zythecan, Lourtothecan, Mitoxantrone, Pirarubicin, Pixanthrone, Rubitecan, Bovine One or more agents selected from the group consisting of triacid, SN-38, tafluposide, and topotecan, and combinations thereof;

● 면역학적 제제에는 인터페론 및 다수의 면역증진제가 포함된다. 인터페론에는 인터페론 알파, 인터페론 알파-2a, 인터페론 알파-2b, 인터페론 베타, 인터페론 감마-1a 또는 인터페론 감마-n1이 포함된다. 그 밖의 다른 약제에는 필그라스팀, 렌티난, 시조필란, 테라시스 (TheraCys), 유베니멕스, WF-10, 알데스로이킨, 알렘투주마브, BAM-002, 다카르바진, 다클리주마브, 데니로이킨, 젬투주마브, 오조가미신, 이브리투모마브, 이미퀴모드, 레노그라스팀, 렌티난, 흑색종 백신 (코리악스 (Coriax)), 몰그라모스팀, 온코박스 (OncoVAX)-CL, 사르그라모스팀, 타소네르민, 테클로이킨, 티말라신, 토시투모마브, 비룰리진 (Virulizin), Z-100, 에프라투주마브, 미투모마브, 오레고보마브, 펨투모마브, 프로벤지 (Provenge)가 포함된다;Immunological preparations include interferon and a number of immunostimulants. Interferons include interferon alpha, interferon alpha-2a, interferon alpha-2b, interferon beta, interferon gamma-1a or interferon gamma-n1. Other drugs include filgrastim, lentinan, schizophyllan, theracys, juvenimex, wf-10, aldes leukin, alemtuzumab, bam-002, dacarbazine, daclizumab, denny Leukin, gemtuzumab, ozogamicin, ibritumomab, imiquimod, renograstim, lentinan, melanoma vaccine (Coriax), molgramos team, OncoVAX-CL, sar Grammoth Team, Tasornermin, Teclokin, Timalacin, Tositumomab, Virulizin, Z-100, Epratuzumab, Mitumomab, Oregombomab, Femtomomab, Provenge (Provenge) ) Is included;

● 생물학적 반응 변형제는 조직세포의 생존, 성장 또는 분화와 같은 생체의 방어기전 또는 생물학적 반응을 이들이 항종양 활성을 갖도록 지시하게 변형시키는 약제이다. 이러한 약제는 크레스틴, 렌티난, 시조피란, 피시바닐 또는 유베니멕스를 포함한다;Biological response modifiers are agents that modify biological defense mechanisms or biological responses such as survival, growth or differentiation of tissue cells to direct them to have antitumor activity. Such agents include crestine, lentinan, sizopyran, fishvanil or ubenimex;

● 그 밖의 다른 항암제에는 알리트레티노인, 암플리젠, 아트라센탄 벡사로텐, 보르테조미브, 보센탄 (Bosentan), 칼시트리올, 엑시술린드, 피나스테라이드, 포테무스틴, 이반드론산, 밀테포신, 미톡산트론, l-아스파라기나제, 프로카르바진, 다카르바진, 하이드록시카바마이드, 페가스파르가제, 펜토스타틴, 타자로텐, TLK-286, 벨케이드 (Velcade), 타르세바 (Tarceva) 또는 트레티노인이 포함된다;Other anticancer agents include atritretinoin, ampplizen, atrasentan bexarotene, bortezomib, bosentan, calcitriol, excisulind, finasteride, fortemustine, ibandronic acid, mittefosin and mitoxane Contains tron, l-asparaginase, procarbazine, dacarbazine, hydroxycarbamide, pegaspargase, pentostatin, tazarotene, TLK-286, Velcade, Tarceva or tretinoin do;

● 그 밖의 다른 항혈관형성 화합물에는 아시트레틴, 펜레티나이드, 탈리도마이드, 졸레드론산, 안지오스타틴, 아플리딘, 실렝타이드, 콤브레타스타틴 A-4, 엔도스타틴, 할로푸지논, 레비마스타트, 레모바브, 레블리미드 (Revlimid), 스쿠알라민, 유라킨 및 비탁신 (Vitaxin)이 포함된다;Other anti-angiogenic compounds include acitretin, fenretinide, thalidomide, zoledronic acid, angiostatin, aplidine, celentide, combretastatin A-4, endostatin, halofuginone, levimastat, remobarb , Revlimid, squalane, urakin and bitaxin;

● 백금-배위결합된 화합물에는 시스플라틴, 카르보플라틴, 네다플라틴 또는 옥살리플라틴이 포함되나, 이들로 제한되지는 않는다;Platinum-coordinated compounds include, but are not limited to, cisplatin, carboplatin, nedaplatin or oxaliplatin;

● 캄프토테신 유도체에는 캄프토테신, 10-하이드록시캄프토테신, 9-아미노캄프토테신, 이리노테칸, SN-38, 에도테카린 및 토포테칸이 포함되나, 이들로 제한되지는 않는다;Camptothecin derivatives include, but are not limited to, camptothecin, 10-hydroxycamptothecin, 9-aminocamptothecin, irinotecan, SN-38, edotecarin and topotecan;

● 타이로신 키나제 억제제는 이레사 (Iressa) 또는 SU5416이다;The tyrosine kinase inhibitor is Iressa or SU5416;

● 항체에는 헤르셉틴 (Herceptin), 에르비툭스 (Erbitux), 아바스틴 (Avastin) 또는 리툭시마브 (Rituximab)가 포함된다;Antibodies include Herceptin, Erbitux, Avastin or Rituximab;

● 인터페론에는 인터페론 알파, 인터페론 알파-2a, 인터페론 알파-2b, 인터페론 베타, 인터페론 감마-1a 또는 인터페론 감마-n1이 포함된다;Interferons include interferon alpha, interferon alpha-2a, interferon alpha-2b, interferon beta, interferon gamma-1a or interferon gamma-n1;

● 생물학적 반응 변형제는 조직세포의 생존, 성장 또는 분화와 같은 생체의 방어기전 또는 생물학적 반응을 이들이 항종양 활성을 갖도록 지시하게 변형시키는 약제이다. 이러한 약제는 크레스틴, 렌티난, 시조피란, 피시바닐 또는 유베니멕스 를 포함한다; 및Biological response modifiers are agents that modify biological defense mechanisms or biological responses such as survival, growth or differentiation of tissue cells to direct them to have antitumor activity. Such agents include crestine, lentinan, sizopyran, fishvanil or ubenimex; And

그 밖의 다른 항종양제에는 미톡산트론, l-아스파라기나제, 프로카르바진, 다카르바진, 하이드록시카바마이드, 펜토스타틴, 또는 트레티노인이 포함된다.Other anti-tumor agents include mitoxantrone, l-asparaginase, procarbazine, dacarbazine, hydroxycarbamide, pentostatin, or tretinoin.

본 명세서에서 사용된 것으로서 "비정상적인 세포성장"은 다른 식으로 지적되지 않는 한은 정상적인 조절기전과는 무관한 세포성장을 의미한다 (예를 들어, 접촉억제의 상실). 이것은 (1) 돌연변이된 타이로신 키나제를 발현시키거나, 수용체 타이로신 키나제의 과발현에 의해서 증식하는 종양세포 (종양); (2) 비정상 타이로신 키나제 활성화가 일어나는 그 밖의 다른 증식성 질환의 양성 및 악성 세포; (4) 수용체 타이로신 키나제에 의해서 증식하는 모든 종양; (5) 비정상 세린/트레오닌 키나제 활성화에 의해서 증식하는 모든 종양; 및 (6) 비정상 세린/트레오닌 키나제 활성화가 일어나는 그 밖의 다른 증식성 질환의 양성 및 악성 세포의 비정상적인 성장을 포함한다.As used herein, “abnormal cell growth” refers to cell growth independent of normal regulatory mechanisms unless otherwise indicated (eg, loss of contact inhibition). These include (1) tumor cells (tumors) that express mutated tyrosine kinases or proliferate by overexpression of receptor tyrosine kinases; (2) benign and malignant cells of other proliferative diseases in which abnormal tyrosine kinase activation occurs; (4) all tumors that proliferate by receptor tyrosine kinases; (5) all tumors that proliferate by abnormal serine / threonine kinase activation; And (6) benign growth of other proliferative diseases in which abnormal serine / threonine kinase activation occurs and abnormal growth of malignant cells.

본 발명의 화합물은 FAK 단백질 타이로신 키나제의 강력한 억제제이며, 따라서 포유동물, 특히 인간에게서 항증식제 (예를 들어, 항암제), 항종양제 (예를 들어, 고형 종양에 대해 유효함), 항혈관형성제 (예를 들어, 혈관의 증식을 정지 또는 방지함)로서의 치료학적 용도에 매우 적합하다. 특히, 본 발명의 화합물은 간, 신장, 방광, 유방, 위, 난소, 결장직장, 전립선, 췌장, 폐, 외음부, 갑상선, 간암, 육종, 신경교아세포종, 두경부, 및 피부의 양성 과형성증 (예를 들어, 건선) 및 전립선의 양성 과형성증 (예를 들어, BPH)과 같은 그 밖의 다른 과형성 상태와 같은 다양한 인간 과증식성 질환의 예방 및 치료에 유용하다. 또한, 본 발명의 화합물 은 광범위한 백혈병 및 림프구성 림프종에 대해서 활성을 가질 수 있다.Compounds of the present invention are potent inhibitors of FAK protein tyrosine kinases and are therefore antiproliferative (eg anticancer agents), antitumor agents (eg effective against solid tumors), antivascularity in mammals, especially humans It is well suited for therapeutic use as a forming agent (eg, to stop or prevent the proliferation of blood vessels). In particular, the compounds of the present invention may be used in the liver, kidney, bladder, breast, stomach, ovary, colorectal, prostate, pancreas, lung, vulva, thyroid, liver cancer, sarcoma, glioblastoma, head and neck, and benign hyperplasia of the skin (eg It is useful for the prevention and treatment of various human hyperproliferative diseases such as, for example, psoriasis) and other hyperplastic conditions such as benign hyperplasia of the prostate (eg, BPH). In addition, the compounds of the present invention may have activity against a wide range of leukemias and lymphocytic lymphomas.

본 발명의 한가지 바람직한 구체예에서, 암은 폐암, 골암, 췌장암, 위암, 피부암, 두경부암, 피부 또는 안내 흑색종, 자궁암, 난소암, 부인과암, 직장암, 항문 부위의 암, 위암, 결장암, 유방암, 자궁암, 난관암, 자궁내막암, 경부암, 질암, 외음부암, 호지킨병, 식도암, 소장암, 내분비계의 암, 갑상선암, 부갑상선암, 부신암, 연조직의 육종, 요도암, 음경암, 편평세포암, 전립선암, 만성 또는 급성 백혈병, 림프구성 림프종, 방광암, 신장 또는 요관의 암, 신세포암, 신우암, 중추신경계 (CNS)의 신생물, 원발성 CNS 림프종, 척수축 종양, 뇌암, 뇌하수체 선종, 또는 전술한 암 중의 하나 또는 그 이상의 조합으로 부터 선택된다.In one preferred embodiment of the invention, the cancer is lung cancer, bone cancer, pancreatic cancer, gastric cancer, skin cancer, head and neck cancer, skin or intraocular melanoma, uterine cancer, ovarian cancer, gynecological cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, breast cancer , Uterine cancer, fallopian tube cancer, endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, Hodgkin's disease, esophageal cancer, small intestine cancer, cancer of the endocrine system, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penis cancer, squamous cancer Cell cancer, prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvis, neoplasm of central nervous system (CNS), primary CNS lymphoma, spinal contraction tumor, brain cancer, pituitary adenoma Or a combination of one or more of the foregoing arms.

더욱 바람직한 구체예에서, 암은 유방암, 폐암, 결장암, 뇌암, 전립선암, 위암, 췌장암, 난소암, 피부암 (흑색종), 내분비계암, 자궁암, 고환암 및 방광암과 같은 (단, 이들로 제한되지는 않는다) 고형 종양으로부터 선택된다.In a more preferred embodiment, the cancer is but is not limited to breast cancer, lung cancer, colon cancer, brain cancer, prostate cancer, gastric cancer, pancreatic cancer, ovarian cancer, skin cancer (melanoma), endocrine cancer, uterine cancer, testicular cancer and bladder cancer Solid tumors).

본 발명의 화합물은 또한, 비정상 발현 리간드/수용체 상호작용 또는 활성화 또는 다양한 단백질 타이로신 키나제에 관련된 시그날링 이벤트 (signalling event)가 연루되는 추가의 질환의 치료에 유용할 수도 있다. 이러한 질환에는 erbB 타이로신 키나제의 비정상 기능, 발현, 활성화 또는 시그날링이 연루된 뉴론, 신경교, 성상세포, 시상하부, 및 그 밖의 다른 선, 대식세포, 상피세포, 기질 및 포배강 성질의 질환이 포함될 수 있다. 또한, 본 발명의 화합물은 본 발명의 화합물에 의해서 억제되는 확인 및 아직 미확인된 타이로신 키나제 둘 다가 연루된 염증성, 혈관형성성 및 면역학적 질환에서 치료학적 유용성을 가질 수도 있다.The compounds of the invention may also be useful for the treatment of additional diseases involving abnormal expression ligand / receptor interactions or activation or signaling events related to various protein tyrosine kinases. Such diseases may include disorders of neurons, glial, astrocytic, hypothalamus, and other glandular, macrophage, epithelial, stromal and blastocyst properties involving abnormal function, expression, activation or signaling of erbB tyrosine kinases. have. In addition, the compounds of the present invention may have therapeutic utility in inflammatory, angiogenic and immunological diseases involving both identified and yet unidentified tyrosine kinases inhibited by the compounds of the present invention.

본 발명의 특별한 관점은 저골량 (low bone mass) 치료량의 화학식 1의 화합물 또는 이 화합물의 약제학적으로 허용되는 염을 존재하는 상태의 치료가 필요한 포유동물에게 투여하는 것을 포함하여 포유동물 (인간을 포함)에서 저골량을 나타내는 상태를 치료 또는 예방하는 방법에 관한 것이다.A particular aspect of the present invention includes administering a mammal (human being to a mammal in need thereof by administering a low bone mass therapeutic amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof to a mammal in need thereof. It includes a method for treating or preventing a condition showing low bone mass.

본 발명은 특히, 저골량을 나타내는 상태가 골다공증, 무름 (frailty), 골다공성 골절, 골결손 (bone defect), 소아 특발성 골손실, 포상 (alveolar) 골손실, 하악골 골손실, 골골절, 절골술, 치주염 또는 보철 내방성장 (prosthetic ingrowth)인 상기한 방법에 관한 것이다.In particular, the present invention is a condition showing low bone mass, osteoporosis, frailty, osteoporotic fracture, bone defect, idiopathic bone loss, alveolar bone loss, mandibular bone loss, fracture, osteotomy, It relates to the above-described method of periodontitis or prosthetic ingrowth.

본 발명의 특별한 관점은 골다공증 치료량의 화학식 1의 화합물 또는 이 화합물의 약제학적으로 허용되는 염을 이러한 치료가 필요한 포유동물에게 투여하는 것을 포함하여 포유동물 (인간을 포함)에서 골다공증을 치료하는 방법에 관한 것이다.A particular aspect of the invention relates to a method for treating osteoporosis in a mammal, including humans, comprising administering to a mammal in need of such treatment a therapeutic amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof. It is about.

본 발명의 또 다른 관점은 골골절 치료량 또는 골다공성 골절 치료량의 화학식 1의 화합물 또는 이 화합물의 약제학적으로 허용되는 염을 이러한 치료가 필요한 포유동물에게 투여하는 것을 포함하여 포유동물에서 골골절 또는 골다공성 골절을 치료하는 방법에 관한 것이다.Another aspect of the invention includes administering to a mammal in need of such treatment a administering a fracture fracture or osteoporotic fracture therapeutic amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof, to a mammal in need of such treatment A method of treating porous fractures.

용어 "골다공증"은 노인성 골다공증, 폐경기후 골다공증 및 유년기 골다공증과 같은 원발성 골다공증, 및 갑상선기능항진증, 쿠싱증후군 (Cushing syndrome)(코르티코스테로이드 사용에 기인함), 말단비대증, 성선기능저하증, 이골발생 및 저인산혈증과 같은 이차 골다공증을 포함한다.The term "osteoporosis" refers to primary osteoporosis, such as senile osteoporosis, postmenopausal osteoporosis and childhood osteoporosis, and hyperthyroidism, Cushing syndrome (due to the use of corticosteroids), hypertrophy, hypogonadism, dysplasia and hypothyroidism Secondary osteoporosis such as acidemia.

본 명세서에서 사용된 것으로 용어 "치료하는"은 다른 식으로 나타내지 않는 한, 이러한 용어를 적용한 질환 또는 상태, 또는 이러한 질환 또는 상태의 하나 또는 그 이상의 증상을 반전, 경감, 진행의 억제 또는 예방하는 것을 의미한다. 본 명세서에서 사용된 것으로 용어 "치료"는 다른 식으로 나타내지 않는 한, 직전에 정의한 "치료하는"과 같은 치료의 작용을 의미한다.As used herein, the term “treating” refers to reversing, alleviating, inhibiting or preventing a disease or condition to which such term is applied, or one or more symptoms of such disease or condition, unless otherwise indicated. it means. As used herein, the term "treatment" means the action of a treatment, such as "treating" as defined immediately before, unless otherwise indicated.

본 발명은 또한, 약제학적으로 허용되는 보조제, 희석제 또는 담체와 함께 전술한 바와 같이 정의되는 화학식 1의 화합물 또는 그의 약제학적으로 허용되는 염 또는 용매화물을 포함하는 약제학적 조성물을 제공한다.The present invention also provides a pharmaceutical composition comprising a compound of formula 1 or a pharmaceutically acceptable salt or solvate thereof as defined above in association with a pharmaceutically acceptable adjuvant, diluent or carrier.

본 발명은 추가로, 전술한 바와 같이 정의되는 화학식 1의 화합물 또는 그의 약제학적으로 허용되는 염 또는 용매화물을 약제학적으로 허용되는 보조제, 희석제 또는 담체와 혼합시키는 것을 포함하여 본 발명의 약제학적 조성물을 제조하는 방법을 제공한다.The invention further comprises a pharmaceutical composition of the invention comprising admixing a compound of formula 1 or a pharmaceutically acceptable salt or solvate thereof, as defined above, with a pharmaceutically acceptable adjuvant, diluent or carrier It provides a method of manufacturing.

상기 언급된 치료학적 용도를 위해서, 투여되는 투약량은 물론, 사용되는 화합물, 투여의 모드, 원하는 치료 및 지시된 질환에 따라서 달라질 수 있을 것이다. 화학식 1의 화합물/염/용매화물 (활성성분)의 1일 투약량은 1 ㎎ 내지 1 g, 바람직하게는 1 ㎎ 내지 250 ㎎, 더욱 바람직하게는 10 ㎎ 내지 100 ㎎의 범위일 수 있다.For the above mentioned therapeutic uses, the dosage administered will, of course, vary depending on the compound used, the mode of administration, the desired treatment and the condition indicated. The daily dosage of the compound / salt / solvate (active ingredient) of formula 1 may range from 1 mg to 1 g, preferably from 1 mg to 250 mg, more preferably from 10 mg to 100 mg.

본 발명은 또한, 서방성 조성물을 포함한다.The present invention also includes a sustained release composition.

화학식 1의 화합물은 반응식 1에 개략적으로 나타낸 합성경로를 사용하여 제조될 수 있다. 반응식 1에서 치환체는 화학식 1에 대해서 정의된 치환체와 동일한 의미를 갖는다.Compounds of Formula 1 may be prepared using the synthetic routes outlined in Scheme 1. Substituents in Scheme 1 have the same meanings as substituents defined for Formula 1.

Figure 112006082893189-PCT00016
Figure 112006082893189-PCT00016

화학식 1의 화합물은 5-아미노-옥스인돌 (6) 및 피리미딘 (7)을 출발물질로 하여 제조될 수 있다. 화합물 (7)을 불활성 용매 (또는 용매 혼합물) 중에서 10-60분의 기간 동안 -15 내지 45℃ 범위의 온도에서 루이스산과 배합시키고, 이어서 화합물 (6) 및 적합한 염기를 첨가하여 1-24시간 후에 중간체 4-클로로피리미딘 (8)을 고수율로 제공한다. 불활성 용매의 예로는 THF, 1,4-디옥산, n-BuOH, i-PrOH, 디클로로메탄 및 1,2-디클로로에탄이 포함되나, 이들로 제한되지는 않는다. 사용된 적합한 염기의 예로는 (i) 비-친핵성 유기염기, 예를 들어, 트리에틸아민 또는 디이소프로필에틸아민, (ii) 탄산칼륨 또는 탄산세슘과 같은 무기염기, 또는 (iii) MP-카보네이트와 같은 수지 결합된 염기가 포함될 수 있으나, 이들로 제한되지는 않는다.Compounds of formula (1) may be prepared using 5-amino-oxindole (6) and pyrimidine (7) as starting materials. Compound (7) is combined with Lewis acid in an inert solvent (or solvent mixture) at a temperature ranging from -15 to 45 ° C. for a period of 10-60 minutes, followed by 1-24 hours by addition of compound (6) and a suitable base. Intermediate 4-chloropyrimidine (8) is provided in high yield. Examples of inert solvents include, but are not limited to, THF, 1,4-dioxane, n-BuOH, i-PrOH, dichloromethane and 1,2-dichloroethane. Examples of suitable bases used include (i) non-nucleophilic organic bases such as triethylamine or diisopropylethylamine, (ii) inorganic bases such as potassium carbonate or cesium carbonate, or (iii) MP- Resin bound bases such as carbonates may be included, but are not limited to these.

루이스산의 예로는 마그네슘, 구리, 아연, 주석 또는 티타늄의 할라이드 염이 포함되나, 이들로 제한되지는 않는다. 다음 반응에서는, 중간체 (8)을 0 내지 150℃ 범위의 온도에서 그대로 또는 불활성 용매 (또는 용매 혼합물)의 존재하에서 화학식 9의 아민과 반응시켜 화학식 1의 화합물을 제공한다. 임의로, 이 반응은 적합한 염기의 존재하에서 수행될 수 있다. 이 반응에 적합한 용매의 예로는 THF, 1,4-디옥산, DMF, N-메틸-피롤리디논, EtOH, n-BuOH, i-PrOH, 디클로로메탄, 1,2-디클로로에탄, DMSO 또는 아세토니트릴이 포함되나, 이들로 제한되지는 않는다. 적합한 염기는 상기에서 개략적으로 나타낸 바와 같다.Examples of Lewis acids include, but are not limited to, halide salts of magnesium, copper, zinc, tin or titanium. In the next reaction, intermediate (8) is reacted with an amine of formula (9) as such or in the presence of an inert solvent (or solvent mixture) at a temperature in the range of 0 to 150 ° C to give a compound of formula (1). Optionally, this reaction can be carried out in the presence of a suitable base. Examples of suitable solvents for this reaction include THF, 1,4-dioxane, DMF, N-methyl-pyrrolidinone, EtOH, n-BuOH, i-PrOH, dichloromethane, 1,2-dichloroethane, DMSO or aceto Nitriles are included, but are not limited to these. Suitable bases are as outlined above.

본 발명의 화합물은 본 기술분야에서 숙련된 전문가에게 공지된 기술에 의해서 본 발명의 다른 화합물로 합성적으로 변형될 수 있다. 제한없이 설명을 목적으로 간략하게 이러한 방법에는 다음의 반응들이 포함된다:Compounds of the present invention can be synthetically modified to other compounds of the present invention by techniques known to those skilled in the art. For purposes of explanation and not limitation, these methods briefly include the following reactions:

a) 문헌 (T.W. Greene and P.G.M. Wuts, "Protective Groups in Organic Synthesis", Second Edition, John Wiley and Sons, New York, 1991)에 개략적으로 기술된 방법에 의한 보호기의 제거; 예를 들어, HCl 또는 트리플루오로아세트산과 같은 산 공급원에 의한 BOC 보호기의 제거;a) removal of the protecting group by the method outlined in T.W. Greene and P.G.M.Wuts, "Protective Groups in Organic Synthesis", Second Edition, John Wiley and Sons, New York, 1991; Removal of BOC protecting groups, for example, by an acid source such as HCl or trifluoroacetic acid;

b) 일급 또는 이급 아민, 티올 또는 알콜과 같은 (단, 이들로 제한되지는 않는다) 작용기에 의한 이탈기 (할라이드, 메실레이트, 토실레이트 등)의 치환으로 각각 이급 또는 삼급 아민, 티오에테르 또는 에테르의 형성;b) the substitution of leaving groups (halides, mesylates, tosylates, etc.) by functional groups such as, but not limited to, primary or secondary amines, thiols or alcohols, respectively, secondary or tertiary amines, thioethers or ethers Formation of;

c) 문헌 (Thavonekham, B et al. Synthesis (1997), 10, p1189)에서와 같이 페닐 (또는 치환된 페닐) 카바메이트를 일급 또는 이급 아민으로 처리하여 상응하 는 우레아를 형성;c) treating phenyl (or substituted phenyl) carbamate with primary or secondary amines to form the corresponding ureas, as in Thavononekham, B et al. Synthesis (1997), 10 , p1189;

d) 문헌 (Denmark, S.E.; Jones, T.K. J. Org. Chem. (1982) 47, 4595-4597; 또는 van Benthem, R.A.T.M.; Michels, J.J.; Speckamp, W.N. Synlett (1994), 368-370)에서와 같이 프로파질 또는 호모프로파질 알콜 또는 N-BOC 보호된 일급 아민을 나트륨 비스(2-메톡시에톡시)알루미늄 하이드라이드 (Red-Al)로 처리함으로써 상응하는 E-알릴 또는 E-호모알릴 유도체로 환원시킴;d) pro, as in Denmark, SE; Jones, TKJ Org. Chem. (1982) 47, 4595-4597; or van Benthem, RATM; Michels, JJ; Speckamp, WN Synlett (1994), 368-370). Reduction of the corresponding E-allyl or E-holy allyl derivatives by treatment of the phazyl or homopropazyl alcohol or N-BOC protected primary amine with sodium bis (2-methoxyethoxy) aluminum hydride (Red-Al) ;

e) 문헌 (Tomassy, B. et.al. Synth. Commun. (1998), 28, p.1201)에서와 같이 알킨을 수소 가스 및 Pd 촉매로 처리함으로써 상응하는 Z-알켄 유도체로 환원시킴;e) reduction of the alkyne to the corresponding Z-alkene derivative by treatment with hydrogen gas and a Pd catalyst as in Tomassy, B. et.al. Synth.Commun. (1998), 28 , p. 1201;

f) 일급 및 이급 아민을 이소시아네이트, 산 클로라이드 (또는 그 밖의 다른 활성화된 카복실산 유도체), 알킬/아릴 클로로포르메이트 또는 설포닐 클로라이드로 처리하여 상응하는 우레아, 아미드, 카바메이트 또는 설폰아미드를 제공함;f) treating the primary and secondary amines with isocyanates, acid chlorides (or other activated carboxylic acid derivatives), alkyl / aryl chloroformates or sulfonyl chlorides to provide the corresponding ureas, amides, carbamates or sulfonamides;

g) 알데히드 또는 케톤 및 적절한 환원시약을 사용한 일급 또는 이급 아민의 환원적 아미노화;g) reductive amination of primary or secondary amines with aldehydes or ketones and appropriate reducing reagents;

h) 알콜을 이소시아네이트, 산 클로라이드 (또는 그 밖의 다른 활성화된 카복실산 유도체), 알킬/아릴 클로로포르메이트 또는 설포닐 클로라이드로 처리하여 상응하는 카바메이트, 에스테르, 카보네이트 또는 설폰산 에스테르를 제공함.h) Treatment of the alcohol with isocyanates, acid chlorides (or other activated carboxylic acid derivatives), alkyl / aryl chloroformates or sulfonyl chlorides to give the corresponding carbamate, ester, carbonate or sulfonic acid esters.

화학식 9의 아민은 직접 구입하여 사용할 수 있거나, 또는 통상적인 화학적 변형방법을 사용하여 본 기술분야에서 숙련된 전문가에 의해서 제조될 수 있다. 예를 들어, 아릴알킬아민 또는 헤테로아릴알킬아민은 Pd/C 또는 라니 니켈 (Raney Nickel)과 같은 촉매를 사용한 촉매적 수소화반응에 의해서, 또는 리튬 알루미늄 하이드라이드 환원반응에 의해서 상응하는 니트릴로부터 제조될 수 있다 (참조: Rylander, Catalytic Hydrogenation in Organic Synthesis, Academic Press, 1979).The amines of formula 9 can be purchased directly or used by those skilled in the art using conventional chemical modification methods. For example, arylalkylamines or heteroarylalkylamines can be prepared from the corresponding nitriles by catalytic hydrogenation with a catalyst such as Pd / C or Raney Nickel, or by lithium aluminum hydride reduction. (Rylander, Catalytic Hydrogenation in Organic Synthesis, Academic Press, 1979).

Figure 112006082893189-PCT00017
Figure 112006082893189-PCT00017

니트릴 출발물질은 구입할 수 있거나, 문헌 (Tschaen, D.W., et. al. Synthetic Communications (1994), 24, 6, pp 887-890)에 기술된 Pd 커플링 조건을 사용하여 상응하는 아릴/헤테로아릴 브로마이드, 요오다이드 또는 트리플레이트 및 Zn(CN)2로부터 제조될 수 있다.Nitrile starting materials can be purchased or the corresponding aryl / heteroaryl bromide using the Pd coupling conditions described in Tschaen, DW, et.al. Synthetic Communications (1994), 24, 6, pp 887-890. , Iodide or triflate and Zn (CN) 2 .

Figure 112006082893189-PCT00018
Figure 112006082893189-PCT00018

대안적으로, 벤질아민 또는 헤테로아릴메틸아민은 적절한 아릴알킬 또는 헤테로아릴알킬 할라이드 및 (BOC)2NH (기준)의 칼륨염과 반응시키고, 이어서 BOC 기를 산으로 제거함으로써 제조될 수 있다.Alternatively, benzylamine or heteroarylmethylamine can be prepared by reacting with a suitable arylalkyl or heteroarylalkyl halide and potassium salt of (BOC) 2 NH (reference), followed by removal of the BOC group with acid.

Figure 112006082893189-PCT00019
Figure 112006082893189-PCT00019

화학식 9의 아민, 아민의 보호된 형태, 아민에 대한 전구체 및 아민의 보호된 형태에 대한 전구체는 문헌 (Tsuji, J.; Palladium Reagents and Catalysts, John Wiley and Sons 1999) 및 이 문헌에 인용된 문헌에서 기술된 바와 같은 Pd 커 플링 조건을 사용하여 적절한 알킨 또는 알케닐 스타난, 알케닐 보란, 알케닐 보론산, 보론산 에스테르를 적절한 아릴 또는 헤테로아릴 브로마이드, 요오다이드 또는 트리플레이트와 결합시킴으로써 제조될 수 있다.Amines of formula (9), protected forms of amines, precursors to amines and precursors to protected forms of amines are described in Tsuji, J .; Palladium Reagents and Catalysts, John Wiley and Sons 1999 and references cited therein. Prepared by combining the appropriate alkyne or alkenyl stanan, alkenyl borane, alkenyl boronic acid, boronic ester with the appropriate aryl or heteroaryl bromide, iodide or triflate using Pd coupling conditions as described in Can be.

Figure 112006082893189-PCT00020
Figure 112006082893189-PCT00020

화학식 9의 적절하게 보호된 아민은 본 기술분야에서 숙련된 전문가에게 친숙한 방법, 예를 들어, 이하의 방법에 따라서 화학식 9의 상이한 아민으로 전환될 수 있다:Appropriately protected amines of formula 9 can be converted to different amines of formula 9 according to methods familiar to those skilled in the art, for example,

(a) 티오에테르의 설폭사이드 또는 설폰으로의 산화반응:(a) Oxidation of thioether to sulfoxide or sulfone:

Figure 112006082893189-PCT00021
Figure 112006082893189-PCT00021

(b) 설파닐리드의 N-알킬화 반응은 문헌 (Brehme, R. "Synthesis", (1976), pp 113-114)에 기술된 조건을 사용하여 상전이 하에서 달성될 수 있다:(b) N-alkylation of sulfanilide can be achieved under phase transition using the conditions described in Brehme, R. "Synthesis", (1976), pp 113-114:

Figure 112006082893189-PCT00022
Figure 112006082893189-PCT00022

본 기술분야에서 숙련된 전문가에 의해서 이해되는 바와 같이, 아릴 할라이드 또는 트리플레이트 또는 헤테로아릴 할라이드 또는 트리플레이트의 방향족 또는 헤테로방향족 아민으로의 화학적 변형반응은 문헌 (참조: Hartwig, J.F.: "Angew. Chem. Int. ED." (1998), 37, pp. 2046-2067, Wolfe, J.P.; Wagaw, S.; Marcoux, J.F.; Buchwald, S.L.; "Acc. Chem. Res.", (1998), 31, pp 805-818, Wolfe, J.P.; Buchwald, S.L.; "J. Org. Chem.", (2000), 65, pp 1144-1157, Muci, A.R.; Buchwald, S.L.; "Topics in Current Chemistry" (2002), pp. 131-209, 및 이들 문헌에 인용된 문헌)에 현재 개략적으로 기술된 조건을 사용하여 수행될 수 있다. 추가로, 본 기술분야에서 숙련된 전문가에 의해서 이해되는 바와 같이, 이들 동일한 아릴 또는 헤테로아릴 아미노화 화학적 변형반응은 니트릴 (또는 일급 아미드) 전구체에 대해서 수행되어, 니트릴 (또는 아미드) 환원시킨 후에 화학식 5의 아민을 제공할 수 있다. 화학식 5의 보호된 아민은 본 기술분야에서 숙련된 전문가에게 친숙한 방법에 따라서 화학식 5의 상이한 아민으로 더 전환될 수 있다.As will be appreciated by those skilled in the art, chemical modification of aryl halides or triflate or heteroaryl halides or triflate to aromatic or heteroaromatic amines is described in Hartwig, JF: "Angew. Chem. Int. ED. "(1998), 37, pp. 2046-2067, Wolfe, JP; Wagaw, S .; Marcoux, JF; Buchwald, SL;" Acc. Chem. Res. ", (1998), 31, pp 805-818, Wolfe, JP; Buchwald, SL; "J. Org. Chem.", (2000), 65, pp 1144-1157, Muci, AR; Buchwald, SL; "Topics in Current Chemistry" (2002) , pp. 131-209, and references cited therein). In addition, as understood by those skilled in the art, these same aryl or heteroaryl amination chemical modifications are carried out on nitrile (or primary amide) precursors, followed by the reduction of nitrile (or amide) 5 amines may be provided. Protected amines of formula (5) may be further converted to different amines of formula (5) according to methods familiar to those skilled in the art.

Figure 112006082893189-PCT00023
Figure 112006082893189-PCT00023

화학식 1의 화합물의 시험관내 활성은 이하의 방법에 의해서 측정될 수 있다. 더욱 특히, 이하의 시험은 화학식 1의 화합물이 촉매적 구조물 FAK(410-689)의 타이로신 키나제 활성을 억제하는지 여부를 측정하는 방법을 제공한다. 이 시험은 FAK(410-689)에 의한 폴리-glu-tyr 포스포릴화의 억제를 측정하는 ELISA-기재 형식이다.In vitro activity of the compound of formula 1 can be measured by the following method. More particularly, the following test provides a method of determining whether a compound of Formula 1 inhibits tyrosine kinase activity of the catalytic construct FAK (410-689). This test is an ELISA-based format that measures the inhibition of poly-glu-tyr phosphorylation by FAK (410-689).

시험 프로토콜은 다음의 3 부분을 갖는다:The test protocol has three parts:

I. His-FAK(410-689)의 정제 및 분해I. Purification and Degradation of His-FAK (410-689)

II. FAK410-689 (a.k.a. FAKcd) 활성화II. Activating FAK410-689 (a.k.a.FAKcd)

III. FAKcd 키나제 ELISAIII. FAKcd kinase ELISA

재료:material:

- Ni-NTA 아가로즈 (Qiagen)Ni-NTA agarose (Qiagen)

- XK-16 칼럼 (Amersham-Pharmacia)XK-16 column (Amersham-Pharmacia)

- 300 mM 이미다졸300 mM imidazole

- 슈퍼덱스 2000 하이로드 (Superdex 2000 HiLoad) 16/60 정제등급 (prep grade) 칼럼 (Amersham Biotech.)Superdex 2000 HiLoad 16/60 prep grade column (Amersham Biotech.)

- 항체: 항-포스포타이로신 HRP-컨쥬게이트된 Py20 (Transduction Labs.)Antibodies: anti-phosphotyrosine HRP-conjugated Py20 (Transduction Labs.)

- FAKcd: 자가 정제 및 활성화됨FAKcd: self-purified and activated

- TMB 마이크로웰 퍼옥시다제 기질 (Oncogene Research Products #CL07)TMB microwell peroxidase substrate (Oncogene Research Products # CL07)

- BSA: Sigma #P1379-BSA: Sigma # P1379

- DMSO: Sigma #D-5879DMSO: Sigma # D-5879

- D-PBS: Gibco #14190-037-D-PBS: Gibco # 14190-037

정제용 시약:Purifying Reagents:

- 완충액 A: 50 mM HEPES pH 7.0, 500 mM NaCl, 0.1 mM TCEP, 완전 TM 프로테아제 억제제 칵테일 정제 (cocktail tablets)(Roche)Buffer A: 50 mM HEPES pH 7.0, 500 mM NaCl, 0.1 mM TCEP, full TM protease inhibitor cocktail tablets (Roche)

- 완충액 B: 25 mM HEPES pH 7.0, 400 mM NaCl, 0.1 mM TCEPBuffer B: 25 mM HEPES pH 7.0, 400 mM NaCl, 0.1 mM TCEP

- 완충액 C: 10 mM HEPES pH 7.5, 200 mM 황산암모늄, 0.1 mM TCEP.Buffer C: 10 mM HEPES pH 7.5, 200 mM ammonium sulfate, 0.1 mM TCEP.

활성화용 시약Activation reagent

- FAK(410-689): 1.48 ㎎/㎖로 총 450 ㎕에 대하여 150 ㎕/튜브씩으로 3개의 튜브의 동결된 분취액 (660 ㎍)FAK (410-689): frozen aliquots of three tubes (660 μg) at 150 μl / tube for a total of 450 μl at 1.48 mg / ml

- His-Src(249-524): 10 mM HEPES, 200 mM (NH4)2SO4 중의 ~0.74 ㎎/㎖ 원액His-Src (249-524): 10 mM HEPES, 200 mM (NH 4 ) 2 SO 4 -0.74 mg / ml stock solution in

- Src 반응 완충액 (Upstate Biotech): 100 mM 트리스-HCl pH 7.2, 125 mM MgCl2, 25 mM MnCl2, 2 mM EDTA, 250 μM Na3VO4, 2 mM DTTSrc reaction buffer (Upstate Biotech): 100 mM Tris-HCl pH 7.2, 125 mM MgCl 2 , 25 mM MnCl 2 , 2 mM EDTA, 250 μM Na 3 VO 4 , 2 mM DTT

- Mn2 +/ATP 칵테일 (Upstate Biotech): 75 mM MnCl2, 500 μM ATP, 20 mM MOPS pH 7.2, 1 mM Na3VO4, 25 mM □-글리세롤 포스페이트, 5 mM EGTA, 1 mM DTT- Mn 2 + / ATP cocktail (Upstate Biotech): 75 mM MnCl 2, 500 μM ATP, 20 mM MOPS pH 7.2, 1 mM Na 3 VO 4, 25 mM □ - glycerol phosphate, 5 mM EGTA, 1 mM DTT

- ATP: 150 mM 원액ATP: 150 mM stock solution

- MgCl2: 1 mM 원액MgCl 2 : 1 mM stock solution

- DTT: 1 M 원액-DTT: 1 M stock

FAKcdFAKcd 키나제Kinase ELISAELISA 용 시약:Reagent for:

- 포스포릴화 완충액: 50 mM HEPES, pH 7.5, 125 mM NaCl, 48 mM MgCl2 Phosphorylation buffer: 50 mM HEPES, pH 7.5, 125 mM NaCl, 48 mM MgCl 2

- 세척 완충액: TBS + 0.1％ 트윈-20Wash buffer: TBS + 0.1% Tween-20

- 차단 완충액: 트리스 완충 식염수, 3％ BSA, 0.05％ 트윈-20, 여과됨.Blocking buffer: Tris buffered saline, 3% BSA, 0.05% Tween-20, filtered.

- 플레이트 코팅 완충액: 포스페이트 완충 식염수 (DPBS) 중의 50 ㎎/㎖ 폴리-Glu-Tyr (Sigma #P0275)Plate coating buffer: 50 mg / ml poly-Glu-Tyr (Sigma # P0275) in phosphate buffered saline (DPBS)

- ATP: H2O 또는 HEPES 중의 0.1 M ATP, pH 7ATP: 0.1 M ATP in H 2 O or HEPES, pH 7

주) ATP 시험 완충액: 120 ㎕ 반응용적 중의 80 ㎕가 50 μM 최종 ATP 농도가 되도록 PBS 중에서 75 μM ATP로 만든다.NOTE ATP Test Buffer: Make 75 μM ATP in PBS so that 80 μl in 120 μl reaction volume is at 50 μM final ATP concentration.

I. I. HisHis -- FAKcdFAKcd (410-689)의 정제(410-689) tablets

1. 3 용적 (400 ㎖)의 완충액 A 중에 과발현된 His-FAKcd410-689 재조합 단백질을 함유하는 130 g의 바큘로바이러스 세포 페이스트를 재현탁시킨다.1. Resuspend 130 g of baculovirus cell paste containing His-FAKcd410-689 recombinant protein overexpressed in 3 volumes (400 mL) of Buffer A.

2. 세포를 마이크로유동화기 (microfluidizer) 상에 1회 통과시켜 용해시킨다.2. The cells are lysed once through a microfluidizer.

3. 소르발 (Sorval) SLA-1500 회전자 (rotor)에서 35분 동안 14,000 rpm으로 4℃에서 원심분리하여 세포 파편을 제거한다.3. Sorval Remove cell debris by centrifugation at 4 ° C. at 14,000 rpm for 35 minutes on a SLA-1500 rotor.

4. 상등액을 깨끗한 튜브에 옮기고, 6.0 ㎖의 Ni-NTA 아가로즈 (Qiagen)를 첨가한다.4. Transfer the supernatant to a clean tube and add 6.0 ml Ni-NTA agarose (Qiagen).

5. 현탁액을 4℃에서 1시간 동안 온화하게 진동시키면서 배양한다.5. Incubate the suspension at 4 ° C. with gentle vibration for 1 hour.

6. 현탁액을 날개 회전자 (swinging bucket rotor)에서 700×g으로 원심분리한다.6. Centrifuge the suspension at 700 × g on a swinging bucket rotor.

7. 상등액을 버리고, 아가로즈 비드를 20.0 ㎖의 완충액 A에 재현탁시킨다.7. Discard the supernatant and resuspend agarose beads in 20.0 mL Buffer A.

8. 비드를 FPLCTM에 연결된 XK-16 칼럼 (Amersham-Pharmacia)에 옮긴다.8. Transfer the beads to an XK-16 column (Amersham-Pharmacia) connected to FPLC ™.

9. 아가로즈-비드를 5 칼럼 용적의 완충액 A로 세척하고, 칼럼을 300 mM 이미다졸을 함유하는 완충액 A의 단계적 구배 (step gradient)로 용출시킨다.9. Agarose-beads are washed with 5 column volumes of Buffer A and the column is eluted with a step gradient of Buffer A containing 300 mM imidazole.

10. 용출된 분획을 완충액 B로 완충액 교환을 수행한다.10. Buffer exchange of the eluted fractions with buffer B.

11. 완충액 교환한 후에, 분획을 모아서 트롬빈을 1:300 (w/w) 비로 첨가하고, 밤새 13℃에서 배양하여 N-말단 His-tag (His-FAK410-698→FAK410-689 (a.k.a. FAKcd))를 제거한다.11. After buffer exchange, the fractions were collected and thrombin added at a ratio of 1: 300 (w / w) and incubated at 13 ° C. overnight to allow N-terminal His-tag (His-FAK410-698 → FAK410-689 (aka FAKcd) ).

12. 반응혼합물을 완충액 B로 평형화된 Ni-NTA 칼럼 상에 다시 첨가하고, 플로우-스로우 (flow-through)를 수거한다.12. The reaction mixture is added again on a Ni-NTA column equilibrated with Buffer B and the flow-through is collected.

13. 플로우-스로우를 1.7 ㎖로 농축시키고, 완충액 C로 평형화된 슈퍼덱스 200 하이로드 16/60 정제등급 칼럼 상에 직접 부하시킨다. 목적하는 단백질은 85-95 ㎖ 사이에서 용출한다.13. Concentrate the flow-throw to 1.7 ml and load directly onto the Superdex 200 High Rod 16/60 Purification Grade column equilibrated with Buffer C. The desired protein elutes between 85-95 ml.

14. FAKcd 단백질을 분취하여 -80℃에서 동결 저장한다.14. Aliquot FAKcd protein and store frozen at -80 ° C.

IIII . . FAKFAK 활성화 Activation

1. 1.48 ㎎/㎖의 FAK(410-689) 450 ㎕ (660 ㎍)에 30 ㎕의 0.037 ㎎/㎖ (1 μM) His-Src(249-524), 30 ㎕의 7.5 mM ATP, 12 ㎕의 20 mM MgCl2, 10 ㎕의 Mn2+/ATP 칵테일 (UpState Biotech.), 4 ㎕의 6.7 mM DTT 및 60 ㎕의 Src 반응완충액 (UpState Biotech.)을 첨가한다.1.450 mg (660 μg) of 1.48 mg / mL FAK (410-689) to 30 μl of 0.037 mg / mL (1 μM) His-Src (249-524), 30 μl of 7.5 mM ATP, 12 μl 20 mM MgCl 2 , 10 μl Mn 2+ / ATP cocktail (UpState Biotech.), 4 μl 6.7 mM DTT and 60 μl Src Reaction Buffer (UpState Biotech.) Are added.

2. 반응액을 실온에서 적어도 3시간 동안 배양한다.2. Incubate the reaction solution for at least 3 hours at room temperature.

시간 t0에서 FAK(410-689)의 거의 모두는 단일 포스포릴화된다. 두번째 포스포릴화는 느리다. t120 (t = 120분)에서 10 ㎕의 150 mM ATP를 첨가한다.At time t 0 almost all of the FAK 410-689 is monophosphorylated. The second phosphorylation is slow. Add 10 μl of 150 mM ATP at t 120 (t = 120 min).

T0 = (시작) 90％ 단일 포스포릴화된 FAK(410-689) (1-PO4)T 0 = (Start) 90% single phosphorylated FAK (410-689) (1-PO 4 )

T43 = (43분) 65％ 단일 포스포릴화되고 (1 PO4), 35％ 이중 포스포릴화된다 (2 PO4)T 43 = (43 min) 65% monophosphorylated (1 PO 4 ), 35% double phosphorylated (2 PO 4 )

T90 = (90분) 45％ 1 PO4, 55％ 2 PO4 T 90 = (90 minutes) 45% 1 PO 4 , 55% 2 PO 4

T210 = < 10％ 1 PO4, > 90％ 2 PO4 탈염된 샘플T 210 = <10% 1 PO 4 ,> 90% 2 PO 4 Desalted Sample

3. 탈염된 물질의 180 ㎕ 분취액을 NiNTA 스핀 칼럼 (spin column)에 첨가하고, 스핀 칼럼 상에서 배양한다.3. Add 180 μl aliquots of desalted material to the NiNTA spin column and incubate on the spin column.

4. 10k rpm (microfuge)에서 5분 동안 회전시켜 플로우 스로우 (활성화된 FAK(410-689))를 분리하여 수거하고, His-Src (칼럼상에 포획됨)를 제거한다.4. Rotate for 5 minutes at 10k rpm (microfuge) to separate and collect the flow throw (activated FAK 410-689) and remove His-Src (captured on column).

IIIIII . . FAKcdFAKcd 키나제Kinase ELISAELISA

1. 96-웰 눈크 맥시소르프 플레이트 (Nunc MaxiSorp plate)를 10 ㎍/웰의 폴리-glu-tyr (pGT)로 코팅한다; PBS 중의 10 ㎍/㎖의 pGT를 제조하고, 100 ㎕/웰을 분취한다. 플레이트를 37℃에서 밤새 배양하고, 상등액을 흡인하고, 플레이트를 세척 완충액으로 3 회 세척하고, 4℃에서 저장하기 전에 가볍게 털어서 건조시킨다.1. Coat a 96-well Nunc MaxiSorp plate with 10 μg / well of poly-glu-tyr (pGT); Prepare 10 μg / ml pGT in PBS and aliquot 100 μl / well. The plate is incubated overnight at 37 ° C., the supernatant is aspirated and the plate washed three times with wash buffer and lightly shaken to dry before storage at 4 ° C.

2. 100％ DMSO 중의 2.5 mM의 화합물 원용액을 제조한다. 이어서 원액을 100％ DMSO 중에서 최종 농도의 60×로 희석하고, 키나제 포스포릴화 완충액 중에서 1:5 희석한다.2. Prepare 2.5 mM stock solution in 100% DMSO. The stock is then diluted to 60 × final concentration in 100% DMSO and diluted 1: 5 in kinase phosphorylation buffer.

3. 키나제 포스포릴화 완충액 중의 75 μM 작업 ATP 용액을 제조한다. 50 μM의 최종 ATP 농도를 위해서 각각의 웰에 80 ㎕를 첨가한다.3. Prepare 75 μM working ATP solution in kinase phosphorylation buffer. Add 80 μL to each well for a final ATP concentration of 50 μM.

4. pGT 시험 플레이트의 각각의 웰에 10 ㎕의 희석된 화합물 (0.5log 계열 희석액)을 옮기고, 각각의 화합물은 동일한 플레이트 상에서 3회 주행시킨다.4. Transfer 10 μl of diluted compound (0.5log series dilution) to each well of the pGT test plate and run each compound three times on the same plate.

5. 얼음 상에서 FAKcd 단백질을 키나제 포스포릴화 완충액 중에서 1:1000으로 희석한다. 웰당, 30 ㎕를 분배한다.5. Dilute FAKcd protein 1: 1000 in kinase phosphorylation buffer on ice. Dispense 30 μl per well.

6. 주) 직선성 (linearity) 및 적절한 희석도는 단백질의 각각의 배취에 대하여 미리 결정되어야 한다. 선택된 효소 농도는 효소 시그날의 정량화가 OD450 및 반응속도의 선형 범위에서 대략 0.8-1.0일 것이다.6. NOTE Linearity and appropriate dilution should be predetermined for each batch of protein. The enzyme concentration chosen will be approximately 0.8-1.0 in the linear range of OD450 and reaction rate for quantification of the enzyme signal.

7. 무-ATP 대조군 (노이즈 (noise)) 및 무-화합물 대조군 (시그날) 둘 다를 준비한다.7. Prepare both an ATP-free control (noise) and a compound-free control (signal).

8. (노이즈) 하나의 블랭크 열 (blank row)에는 DMSO 중에서 1:5 희석된 화합물 10 ㎕, 80 ㎕의 포스포릴화 완충액 (- ATP) 및 30 ㎕의 FAKcd 용액을 첨가한다.8. (Noise) To one blank row is added 10 μl of compound diluted 1: 5 in DMSO, 80 μl of phosphorylation buffer (-ATP) and 30 μl of FAKcd solution.

9. (시그날) 대조 웰에는 키나제 포스포릴화 완충액 중에서 1:5 희석된 DMSO (- 화합물) 10 ㎕, 80 ㎕의 75 μM ATP 및 30 ㎕의 1:1000 FAKcd 효소를 첨가한다.9. To (Signal) control wells add 10 μl of DMSO (-compound) diluted 1: 5 in kinase phosphorylation buffer, 80 μl of 75 μM ATP and 30 μl of 1: 1000 FAKcd enzyme.

10. 반응액을 플레이트 진탕기 상에서 온화하게 진탕하면서 실온에서 15분 동안 배양한다.10. Incubate the reaction solution for 15 minutes at room temperature with gentle shaking on a plate shaker.

11. 반응혼합물을 흡인하고, 세척 완충액으로 2회 세척함으로써 반응을 종결시킨다.11. The reaction is terminated by aspirating the reaction mixture and washing twice with wash buffer.

12. 포스포-타이로신 HRP-컨쥬게이트된 (pY20HRP) 항체를 차단 완충액 중에서 0.250 ㎍/㎖ (원액의 1:1000)로 희석한다. 웰당, 100 ㎕씩을 분배하고, 진탕하면서 실온에서 30분 동안 배양한다.12. Dilute phospho-tyrosine HRP-conjugated (pY20HRP) antibody to 0.250 μg / ml (1: 1000 of stock) in blocking buffer. Dispense 100 μl per well and incubate for 30 minutes at room temperature with shaking.

13. 상등액을 흡인하고, 플레이트를 세척 완충액으로 3 회 세척한다.13. Aspirate the supernatant and wash the plate three times with wash buffer.

14. 웰당, 100 ㎕의 실온 TMB 용액을 첨가하여 색상 발현을 개시시킨다. 색상 발현은 웰당, 100 ㎕의 0.09 M H2SO4를 첨가함으로써 대략 15-30초 후에 종결된다.14. Per well, 100 μl of room temperature TMB solution is added to initiate color development. Color development is terminated after approximately 15-30 seconds by adding 100 μl of 0.09 MH 2 SO 4 per well.

15. 시그날은 바이오래드 마이크로플레이트 판독기 (BioRad microplate reader) 또는 OD450에서 판독할 수 있는 마이크로플레이트 판독기 상에서 450 nm에서의 흡광도를 측정함으로써 정량한다.15. Signals are quantified by measuring absorbance at 450 nm on a BioRad microplate reader or a microplate reader that can be read on an OD450.

16. 타이로신 키나제 활성의 억제는 감소된 흡광도 시그날로 나타날 수 있다. 시그날은 일반적으로 0.8-1.0 OD 유니트이다. 이 값은 IC50 μM 농도로 보고된다.16. Inhibition of tyrosine kinase activity may be manifested by reduced absorbance signals. Signals are typically 0.8-1.0 OD units. This value is reported as an IC 50 μM concentration.

FAKFAK 유도성 세포-기재 ELISA: 최종 프로토콜 Inducible Cell-Based ELISA: Final Protocol

재료:material:

리액티-바인드 (Reacti-Bind) 염소 항-토끼 플레이트 96-웰 (Pierce Product#15135ZZ @115.00 USD)Reacti-Bind Goat Anti-Rabbit Plate 96-well (Pierce Product # 15135ZZ @ 115.00 USD)

FAKpY397 토끼 폴리클로날 항체 (Biosource #44624 @315.00 USD)FAKpY397 Rabbit Polyclonal Antibody (Biosource # 44624 @ 315.00 USD)

크롬퓨어 (ChromePure) 토끼 IgG, 전분자 (Jackson Laboratories #001-000-003 @60/25 ㎎ USD)ChromePure Rabbit IgG, Starch (Jackson Laboratories # 001-000-003 @ 60/25 mg USD)

UBI αFAK 클론 2A7 마우스 모노클로날 항체 (Upstate#05-182 @289.00 USD)UBI αFAK Clone 2A7 Mouse Monoclonal Antibody (Upstate # 05-182 @ 289.00 USD)

퍼옥시다제-컨쥬게이트된 아파니퓨어 (AffiniPure) 염소 항-마우스 IgG (Jackson Labs #115-035-146 @95/1.5 ㎖ USD)Peroxidase-conjugated ApiniPure goat anti-mouse IgG (Jackson Labs # 115-035-146 @ 95 / 1.5 ml USD)

슈퍼블럭 (SuperBlock) TBS (Pierce Product#37535ZZ @99 USD)SuperBlock TBS (Pierce Product # 37535ZZ @ 99 USD)

소혈청알부민 (Sigma #A-9647 @117.95/100 g USD)Bovine Serum Albumin (Sigma # A-9647 @ 117.95 / 100 g USD)

TMB 퍼옥시다제 기질 (Oncogene Research Products #CL07-100 ㎖ @40.00 USD)TMB peroxidase substrate (Oncogene Research Products # CL07-100 ml @ 40.00 USD)

Na3VO4 나트륨 오르토바나데이트 (Sigma #S6508 @43.95/50 g USD)Na 3 VO 4 Sodium Orthovanadate (Sigma # S6508 @ 43.95 / 50 g USD)

MTT 기질 (Sigma # M-2128 @25.95/500 ㎎ USD)MTT Substrate (Sigma # M-2128 @ 25.95 / 500 mg USD)

성장배지: DMEM + 10％ FBS, P/S, Glu, 750 ㎍/㎖ 제오신 (Zeocin) 및 50 ㎍/㎖ 하이그로마이신 (Hygromycin; Zeocin InVitrogen #R250-05 @725 USD 및 Hygromycon InVitrogen #R220-05 @150 USD)Growth medium: DMEM + 10% FBS, P / S, Glu, 750 μg / ml Zeocin and 50 μg / ml Hygromycin (Zyocin InVitrogen # R250-05 @ 725 USD and Hygromycon InVitrogen # R220- 05 @ 150 USD)

미페프리스톤 인비트로젠 (Mifepristone InVitrogen) #H110-01 @125 USDMifepristone InVitrogen # H110-01 @ 125 USD

완전 TM EDTA-부재 프로테아제 억제제 펠릿 베링거 만하임 (Boehringer Mannheim) #1873580Full TM EDTA-Free Protease Inhibitor Pellet Boehringer Mannheim # 1873580

키나제-의존성 포스포FAKY397의 선택성을 위한 FAK 세포-기재 프로토콜FAK cell-based protocol for selectivity of kinase-dependent phosphoFAKY397

절차:step:

타이로신 키나제 특이성 억제제를 확인하기 위한 화학적 물질의 스크리닝을 위해서 ELISA 형식의 유도성 FAK 세포-기재 분석이 개발되었다. 세포-기재 분석은 FAK의 발현 및 포스포릴화, 및 잔기 Y397에서의 키나제-의존성 자가포스포릴화 잔기를 외래적으로 조절하기 위하여 진스위치티엠 (GeneSwitchTM) 시스템 (InVitrogen)의 기전을 이용한다.Inducible FAK cell-based assays in ELISA format have been developed for the screening of chemicals to identify tyrosine kinase specific inhibitors. Cell-based assays utilize the mechanism of the GeneSwitch ™ system (InVitrogen) to exogenously regulate the expression and phosphorylation of FAK and kinase-dependent autophosphorylated residues at residue Y397.

Y397에서 키나제-의존성 자가포스포릴화의 억제는 OD450에서 감소된 흡광도 시그날을 나타낸다. 시그날은 일반적으로 0.08 내지 0.1 OD450 유니트의 범위에 속하는 노이즈를 갖는 0.9 내지 1.5 OD450 유니트이다. 이 값은 IC50, μM 농도로 보고된다.Inhibition of kinase-dependent autophosphorylation at Y397 indicates a reduced absorbance signal at OD450. The signal is typically 0.9 to 1.5 OD450 units with noise in the range of 0.08 to 0.1 OD450 units. This value is reported as IC50, μM concentration.

1일에는 T175 플라스크 내에서 A431ㆍFAKwt를 성장시킨다. FAK 세포-시험을 수행하기 전날에 96-웰 U-바닥 플레이트 상의 성장배지에 A431ㆍFAKwt 세포를 접종한다. 세포는 FAK 도입시키기 전에 37℃, 5％ CO2에서 6 내지 8시간 동안 정치시킨다. 100％ 에탄올 중의 10 μM의 미페프리스톤 원용액을 제조한다. 이어서 원용액을 성장배지 내에서 최종 농도의 10×로 희석한다. 10 ㎕의 이 희석액 (0.1 nM 미페프리스톤의 최종 농도)을 각각의 웰에 옮긴다. 세포를 37℃, 5％ CO2에서 밤새 (12 내지 16시간) 정치시킨다. 또한, FAK 발현 및 포스포릴화의 미페프리스톤 유도가 없는 대조 웰을 준비한다.On day 1, A431.FAKwt is grown in a T175 flask. The day before the FAK cell-test, growth medium on 96-well U-bottom plates is inoculated with A431.FAKwt cells. Cells are allowed to stand for 6-8 hours at 37 ° C., 5% CO 2 before FAK introduction. Prepare 10 μM mifepristone stock solution in 100% ethanol. The stock solution is then diluted to 10 × of the final concentration in the growth medium. 10 μl of this dilution (final concentration of 0.1 nM mifepristone) is transferred to each well. The cells are left overnight (12-16 hours) at 37 ° C., 5% CO 2 . In addition, control wells without mifepristone induction of FAK expression and phosphorylation are prepared.

2일째에 염소 항-토끼 플레이트(들)를 슈퍼블럭 TBS 완충액 내에서 제조된 포스포특이적 FAKpY397 폴리클로날 항체 3.5 ㎍/㎖로 코팅하고, 플레이트(들)를 실온에서 2시간 동안 플레이트 진탕기 상에서 진탕한다. 임의로, 대조 웰을 슈퍼블럭 TBS 내에서 제조된 대조 캡쳐 (Capture) 항체 (전체 토끼 IgG 분자) 3.5 ㎍/㎖로 코팅할 수 있다. 과잉의 FAKpY397 항체를 완충액을 사용하여 3회 씻어낸다. 항-FAKpY397 코팅된 플레이트를 플레이트 진탕기 상의 실온에서 1시간 동안 웰당, 200 ㎕의 3％ BSA/0.5％ 트윈 차단 완충액으로 차단한다. 플레이트(들)를 차단하는 한편, 100％ DMSO 중의 5 mM의 화합물 원용액을 제조한다. 이어서 원용액을 100％ DMSO 중에서 최종 농도의 100×로 계열희석한다. 성장배지 내에서 100× 용액을 사용하여 1:10 희석액을 만들고, 10 ㎕의 적절한 화합물 희석액을 37℃, 5％ CO2에서 30분 동안 FAK 유도되거나 비유도된 대조 A431 세포를 함유하는 각각의 웰에 옮긴다. RIPA 용해 완충액 (50 ㎖ 용액당, 50 mM 트리스-HCl, pH 7.4, 1％ NP-40, 0.25％ Na-데옥시콜레이트, 150 mM NaCl, 1 mM EDTA, 1 mM Na3VO4, 1 mM NaF, 및 하나의 완전 TM EDTA-부재 프로테아제 억제제 펠릿)을 제조한다. 30분의 화합물 처리가 종료된 후에, 화합물을 TBS-T 세척 완충액을 사용하여 3 회 세척한다. 세포를 100 ㎕/웰의 RIPA 완충액으로 용해시킨다.On day 2 the goat anti-rabbit plate (s) was coated with 3.5 μg / ml of phosphospecific FAKpY397 polyclonal antibody prepared in superblock TBS buffer and the plate (s) was plate shaker for 2 hours at room temperature. Shake on the stomach. Optionally, control wells can be coated with 3.5 μg / ml control capture antibody (whole rabbit IgG molecule) prepared in superblock TBS. Excess FAKpY397 antibody is washed three times with buffer. Anti-FAKpY397 coated plates are blocked with 200 μl of 3% BSA / 0.5% twin blocking buffer per well for 1 hour at room temperature on a plate shaker. While blocking the plate (s), prepare 5 mM compound stock in 100% DMSO. The original solution is then serially diluted to 100 × of the final concentration in 100% DMSO. Make a 1:10 dilution using a 100 × solution in the growth medium and add 10 μl of the appropriate compound dilution to each well containing FAK induced or underived control A431 cells for 30 minutes at 37 ° C., 5% CO 2 . Move on. RIPA lysis buffer (50 mL solution, 50 mM Tris-HCl, pH 7.4, 1% NP-40, 0.25% Na-deoxycholate, 150 mM NaCl, 1 mM EDTA, 1 mM Na 3 VO 4 , 1 mM NaF , And one complete TM EDTA-free protease inhibitor pellet). After 30 minutes of compound treatment is complete, the compound is washed three times with TBS-T wash buffer. Cells are lysed with 100 μl / well of RIPA buffer.

코팅된 플레이트에 대해서 차단 완충액을 제거하고, TBS-T 세척 완충액을 사용하여 3 회 세척한다. 96-웰 자동화 마이크로디스펜서 (automated microdispenser)를 사용하여 100 ㎕의 전세포-용해물 (단계 6으로부터 유래)을 염소 항-토끼 FAKpY397 코팅된 플레이트(들)에 옮겨 포스포FAKY397 단백질을 포획한다. 실온에서 2시간 동안 진탕한다. 비결합된 단백질을 TBS-T 세척 완충액을 사용하여 3 회 세척한다. 3％ BSA/0.5％ 트윈 차단 완충액 중에서 0.5 ㎍/㎖ (1:2000 희석액)의 UBI αFAK 검출 항체를 제조한다. 웰당, 100 ㎕의 UBI αFAK 용액을 분배하고, 실온에서 30분 동안 진탕한다. TBS-T 세척 완충액을 사용하여 과잉의 UBI αFAK 항체를 3 회 세척한다. 0.08 ㎍/㎖ (1:5000 희석액)의 이차 항- 마우스 퍼옥시다제 (항-2MHRP) 컨쥬게이트된 항체를 제조한다. 웰당, 100 ㎕의 항-2MHRP 용액을 분배하고, 살온에서 30분 동안 진탕한다. 과잉의 항-2MHRP 항체를 TBS-T 세척 완충액을 사용하여 3 회 세척한다. 웰당, 100 ㎕의 실온 TMB 기질용액을 첨가하여 색상이 발현하도록 한다. 웰당, 100 ㎕의 TMB 정지용액 (0.09 M H2SO4)으로 TMB 반응을 종결시키고, 바이오래드 마이크로플레이트 판독기 상에서 450 nm에서의 흡광도를 측정함으로써 시그날을 정량한다.The blocking buffer is removed for the coated plate and washed three times using TBS-T wash buffer. 100 μl of whole cell-lysate (from step 6) is transferred to goat anti-rabbit FAKpY397 coated plate (s) to capture phosphoFAKY397 protein using a 96-well automated microdispenser. Shake for 2 hours at room temperature. Unbound protein is washed three times using TBS-T wash buffer. Prepare 0.5 μg / ml (1: 2000 dilution) of UBI αFAK detection antibody in 3% BSA / 0.5% twin blocking buffer. Per well, dispense 100 μl of UBI αFAK solution and shake for 30 minutes at room temperature. Wash excess UBI αFAK antibody three times using TBS-T wash buffer. Prepare 0.08 μg / mL (1: 5000 dilution) of secondary anti-mouse peroxidase (anti-2MHRP) conjugated antibody. Per well, dispense 100 μl of anti-2MHRP solution and shake for 30 minutes at salon. Excess anti-2MHRP antibody is washed three times with TBS-T wash buffer. Per well, 100 μl of room temperature TMB substrate solution is added to allow color to develop. Per well, the signal is quantified by terminating the TMB reaction with 100 μl of TMB stop solution (0.09 MH 2 SO 4 ) and measuring the absorbance at 450 nm on a Biorad microplate reader.

추가의 FAK 세포시험은 본 발명에서 참고로 포함되어 있다 (Pfizer Attorney Docket No. PC11699 entitled "INDUCIBLE FOCAL ADHESION KINASE CELL ASSAY").Additional FAK cell tests are incorporated herein by reference (Pfizer Attorney Docket No. PC11699 entitled "INDUCIBLE FOCAL ADHESION KINASE CELL ASSAY").

바람직한 구체예에서, 본 발명의 화합물은 예를 들어, 본 명세서에 기술된 것과 같은 키나제 시험에 의해서 측정된 것으로서 500 nM 미만의 시험관내 활성을 갖는다. 바람직하게는, 화합물은 키나제 시험에서 25 nM 미만, 더욱 바람직하게는 10 nM 미만의 IC50을 갖는다. 추가의 바람직한 구체예에서, 화합물은 예를 들어, 본 명세서에 기술된 것과 같은 FAK 세포 기본시험에서 1 μM 미만, 더욱 바람직하게는 100 nM 미만, 가장 바람직하게는 25 nM 미만의 IC50을 나타낸다.In a preferred embodiment, the compounds of the present invention have an in vitro activity of less than 500 nM as measured by, for example, a kinase test as described herein. Preferably, the compound has an IC 50 of less than 25 nM, more preferably less than 10 nM in the kinase test. In a further preferred embodiment, the compound exhibits an IC 50 of less than 1 μM, more preferably less than 100 nM and most preferably less than 25 nM, for example, in a FAK cell basic test as described herein.

더욱 추가로, 이하의 시험(들)을 사용하여 상술한 바와 같은 골다공증 및/또는 저골량을 억제하는 본 발명의 화합물의 능력을 평가할 수 있다.Still further, the following test (s) can be used to assess the ability of a compound of the invention to inhibit osteoporosis and / or low bone mass as described above.

(1) 노화된 온전하고 난소적출된 암컷 (1) Aged, Intact and Ovarian Females 랫트에서In rats 체중,  weight, 체조성Gymnastics 및 골밀도에 대한 시험화합물의 영향 Effect of Test Compounds on Bone and Bone Mineral Density

본 시험을 사용하여 노화된 온전하거나 난소적출된 (OVX) 암컷 랫트 모델에서 시험화합물의 영향을 시험할 수 있다.This test can be used to test the effects of test compounds in aging intact or ovarian isolated (OVX) female rat models.

시험 프로토콜Test protocol

스프라그-도울리 (Sprague-Dawley) 암컷 랫트는 18개월령에서 모의-수술하거나 OVX하는 한편, 랫트의 하나의 군은 기준선 대조군으로서 0일에 부검한다. 수술후 1일에 랫트를 비히클이나 시험화합물로 처리한다. 비히클 또는 시험화합물은 피하주사 (s.c.)에 의해서 1주일에 2회 (화요일 및 금요일) 투여하는데, 시험화합물은 1일에 체중 킬로그램당, 10 밀리그램의 평균 용량으로 투여된다 (10 ㎎/㎏/일).Sprague-Dawley female rats are mock-operated or OVX at 18 months of age, while one group of rats is necropsied on day 0 as a baseline control. One day after surgery, rats are treated with vehicle or test compound. Vehicle or test compound is administered twice a week (Tuesday and Friday) by subcutaneous injection (sc), where the test compound is administered at an average dose of 10 mg per kilogram of body weight per day (10 mg / kg / day) ).

모든 랫트에게 부검하기 2 및 12일 전에 형광성 골 라벨을 위해서 10 ㎎/㎏의 칼세인 (Sigma, St. Louis, MO)을 s.c. 주사로 투여한다. 부검하는 날에 케타민/크실라진 마취 하의 모든 랫트의 체중을 측정하고, 마르고 비만인 체질량 측정을 위한 랫트 전신 스캔 소프트웨어 (Rat Whole Body Scan software)가 장치된 이중-에너지 X-선 흡수측정 (DXA, QDR-4500/W, Hologic Inc., Waltham, MA)을 수행한다. 랫트를 부검한 다음에, 검시하고 심장천자에 의해서 혈액을 수득한다. 각각의 랫트로부터의 원위 대퇴 골간단 (distal femoral metaphysis) 및 대퇴 골간 (shaft)을 말초 정량적 컴퓨터화 단층촬영 (pQCT)에 의해서 분석하고, 용량측정상의 총, 소주성 및 피질성 골 무기질 함량 및 밀도를 측정한다.10 mg / kg calcein (Sigma, St. Louis, Mo.) for fluorescein bone labeling 2 and 12 days prior to necropsy on all rats. Administration by injection. On the day of necropsy, all rats under ketamine / xylazine anesthesia are weighed and dual-energy X-ray absorptiometry (DXA, equipped with Rat Whole Body Scan software for dry and obese body mass determination) QDR-4500 / W, Hologic Inc., Waltham, Mass.). Rats are necropsied, then examined and blood is obtained by cardiac puncture. Distal femoral metaphysis and femoral shaft from each rat were analyzed by peripheral quantitative computed tomography (pQCT), and capacitive total, fibrotic and cortical bone mineral content and density Measure

말초 정량적 컴퓨터화 단층촬영 (pQCT) 분석: 절제된 대퇴골을 소프트웨어 버젼 5.40이 장치된 pQCT X-선 기계 (Stratec XCT Research M, Norland Medical Systems, Fort Atkinson, WI)에 의해서 스캐닝한다. 대퇴골 골간단의 1 밀리미터 (㎜) 두께의 단면을 0.10 ㎜의 복셀 (voxel) 크기를 가지고 원위말단으로부터 5.0 ㎜ (근위 대퇴 골간단, 일차 망상조직성 골위치) 및 13 ㎜ (대퇴 골간, 피질성 골부위) 가까운 위치에서 취한다. 피질성 뼈는 콘투어 모드 (contour mode) 2 및 피질성 모드 4를 사용하여 정의 및 분석한다. 340 ㎎/㎤의 외부 역치 셋팅을 사용하여 연조직으로부터 피질성 외피를 구별하며, 529 ㎎/㎤의 내부 역치를 사용하여 내피질 표면 (endocortical surface)을 따라서 피질성 뼈를 구별한다. 소주성 뼈는 망상조직성 뼈로부터 피질(하)를 구별하기 위하여 655 ㎎/㎤의 역치로 외피모드 (peel mode) 4를 사용하여 결정된다. 규정된 망상조직성 뼈의 1％의 추가의 동심성 외피를 사용하여 피질(하) 뼈가 분석으로부터 배제되는 것을 보장한다. 용량측정성 함량, 밀도 및 면적은 소주성 및 피질성 뼈 둘 다에 대해서 측정된다 (Jamsa T. et al., Bone 23:155-161, 1998; Ke, H.Z. et al., Journal of Bone and Mineral Research, 16:765-773, 2001).Peripheral Quantitative Computed Tomography (pQCT) Analysis: The excised femur is scanned by a pQCT X-ray machine (Stratec XCT Research M, Norland Medical Systems, Fort Atkinson, WI) equipped with software version 5.40. The 1 mm thick section of the femoral metaphyseal has a voxel size of 0.10 mm and 5.0 mm (proximal femoral metaphyseal, primary reticular bone location) and 13 mm (femoral interosseous, cortical) from the distal end. Bone area) Cortical bones are defined and analyzed using contour mode 2 and cortical mode 4. An external threshold setting of 340 mg / cm 3 is used to distinguish cortical envelopes from soft tissues, and an internal threshold of 529 mg / cm 3 is used to distinguish cortical bones along the endocortical surface. Suzhou bones are determined using the Peel Mode 4 with a threshold of 655 mg / cm 3 to distinguish cortex (bottom) from reticular bone. An additional 1% concentric envelope of defined reticular bone is used to ensure that subcortical bone is excluded from the analysis. Dosageable content, density and area are measured for both fibrotic and cortical bone (Jamsa T. et al., Bone 23: 155-161, 1998; Ke, HZ et al., Journal of Bone and Mineral Research , 16: 765-773, 2001).

질의 조직학: 질조직을 파라핀 내에 고정 및 포매시킨다. 5 미크론 절편을 절단하고, 알시안 블루 (Alcian Blue) 염색에 의해서 염색한다. 질내강 상피 두께 및 뮤코폴리사카라이드 (분비된 세포)의 조직학 검사를 수행한다.Histology of the vagina: Vaginal tissue is fixed and embedded in paraffin. 5 micron sections are cut and stained by Alcian Blue staining. Vaginal epithelial thickness and histological examination of mucopolysaccharides (secreted cells) are performed.

프로토콜을 위한 실험군은 다음과 같다:The experimental group for the protocol is as follows:

I 군: 기준선 대조군Group I: baseline control

II 군: 모의 + 비히클Group II: Mock + Vehicle

III 군: OVX + 비히클Group III: OVX + Vehicle

IV 군: OVX + 시험화합물 10 ㎎/㎏/일 (비히클 중에서)Group IV: OVX + Test Compound 10 mg / kg / day (in vehicle)

(2) 골절 치유시험(2) fracture healing test

(a) 전신적 투여 후의 골절 치유에 대한 효과에 대한 시험(a) Test for effect on fracture healing after systemic administration

골절 기술: 3개월령의 스프라그-도울리 랫트를 케타민으로 마취시킨다. 1 ㎝ 절개를 오른쪽 경골 또는 대퇴골의 근위부의 전내측면 상에 만든다. 이하에는 경골 수술기술을 기술하였다. 절개는 뼈를 관통하여 수행되며, 1 ㎜ 구멍을 전릉에 대해서 2 ㎜ 중앙의 경골조면의 원위면에 대하여 4 ㎜ 근접하게 뚫는다. 척수내 못고정 (nailing)은 0.8 ㎜ 스테인레스 스틸 튜브 (최대부하 36.3 N, 최대 강성 (stiffness) 61.8 N/㎜, 뼈와 동일한 조건 하에서 시험됨)를 사용하여 수행된다. 수관의 리밍 (reaming)은 수행되지 않는다. 표준화된 폐쇄골절은 무딘 조우 (jaws)를 갖는 특별히 고안된 조정가능한 겸자를 사용한 3-점 벤딩 (bending)에 의해서 경비골 접합부 2 ㎜ 위에서 생성된다. 연조직 손상을 최소화하기 위하여 골절을 편위시키지 않도록 주의를 기울여야 한다. 피부를 모노필라멘트 나일론 봉합사로 폐쇄시킨다. 수술은 무균조건 하에서 수행된다. 모든 골절의 방사성사진은 못고정한 직후에 찍고, 명시된 골간 영역 외부의 골절을 갖거나, 편위된 못을 갖는 랫트는 제외된다. 나머지 동물은 골절 치유를 시험하는 시점당, 각각의 서브그룹당, 10-12 마리의 동물이 포함되도록 다음의 군들로 무작위적으로 나눈다. 제 1군은 매일 1 ㎖/랫트로 비히클 (물:100％ 에탄올 = 95:5)의 가바즈 (gavage)를 공급받았으며, 그 반면에 다른 군들은 0.01 내지 100 ㎎/㎏/일의 시험할 화합물 (1 ㎖/ 랫트)로부터의 가바즈를 10, 20, 40 및 80일 동안 매일 공급받는다. Fracture technique : Sprague-Dawley rats at 3 months of age are anesthetized with ketamine. A 1 cm incision is made on the anterior medial side of the proximal portion of the right tibia or femur. The tibial surgery technique is described below. The incision is made through the bone and a 1 mm hole is drilled 4 mm close to the distal surface of the tibial surface at the center of 2 mm for the tomb. Intramedullary nailing is performed using a 0.8 mm stainless steel tube (maximum load 36.3 N, maximum stiffness 61.8 N / mm, tested under the same conditions as bone). Reaming of the canal is not performed. Normalized closed fractures are created 2 mm above the nasal medullary joint by 3-point bending using specially designed adjustable forceps with blunt jaws. Care should be taken not to bias the fracture to minimize soft tissue damage. The skin is closed with monofilament nylon sutures. Surgery is performed under aseptic conditions. Radiographs of all fractures are taken immediately after nailing, with the exception of rats with fractures outside the specified interosseous area, or with biased nails. The remaining animals are randomly divided into the following groups to include 10-12 animals, at each time point for testing fracture healing. The first group received daily Gavage (water: 100% ethanol = 95: 5) with 1 ml / rat, while the other groups received 0.01 to 100 mg / kg / day of the compound to be tested. Gabbaz from (1 ml / rat) is fed daily for 10, 20, 40 and 80 days.

10, 20, 40 및 80일에, 각 군으로부터 10-12 마리의 랫트를 케타민으로 마취시키고, 방혈시킴으로써 치사시킨다. 경비골 뼈 모두를 해부하여 제거하고, 모든 연조직을 벗겨낸다. 각 군에 대해서 5-6 마리의 랫트로부터 수득한 뼈를 조직학적 분석을 위해서 70％ 에탄올 중에서 저장하고, 각 군에 대해서 또 다른 5-6 마리의 랫트로부터 수득한 뼈는 방사성사진 및 수행되는 생체역학적 시험을 위해서 완충된 링거용액 (+4℃, pH 7.4) 중에서 저장한다.On days 10, 20, 40 and 80, 10-12 rats from each group are anesthetized with ketamine and killed by bleeding. Dissect and remove all the nasal bones, and remove all soft tissue. Bone from 5-6 rats for each group was stored in 70% ethanol for histological analysis, and bones from another 5-6 rats for each group were radiographed and biopsied performed. Store in buffered Ringer's solution (+ 4 ° C., pH 7.4) for mechanical testing.

조직학적 분석: 골절된 뼈의 조직학적 분석을 위한 방법은 모세킬드 (Mosekilde)와 배크 (Bak)에 의해서 이미 공개되었다 (The Effects of Growth Hormone on Fracture Healing in Rats: A Histological Description. Bone, 14:19-27, 1993). 간략하면, 골절 부위를 골절선의 양쪽까지 8 ㎜를 톱질하고, 메틸메타크릴레이트 중에 포매하여 탈회되지 않게 하고, 라이허트-정 폴리컷트 마이크로톰 (Reichert-Jung Polycut microtome) 상에서 전두 절편을 8 ㎛ 두께로 절단한다. 치료의 존재 및 부재 하에서 골절 치유에 대한 세포성 및 조직 반응을 가시화시키기 위하여 매송-트리크롬 (Masson-Trichrome) 염색된 전두-중앙 절편 (경골 및 비골 둘 다를 포함)을 사용한다. 시리우스 레드 (Sirius red) 염색된 절편을 사용하여 가골구조의 특성을 입증하고, 골절 부위에서 무층골과 층상골 사이를 구분한다. 이하의 측정이 수행된다: (1) 골절 갭 (gap) - 골절에서 피질성 골말단 사이의 최단 간격으로 측정됨, (2) 가골 길이 및 기골 직경, (3) 가골의 총 골용적 면적, (4) 가골 영역 내부의 조직 면적당 뼈조직, (5) 가골 내의 섬유상 조직, 및 (6) 가 골 내의 연골 면적. Histological analysis : Methods for histological analysis of fractured bone have already been published by Mosekilde and Bak (The Effects of Growth Hormone on Fracture Healing in Rats: A Histological Description.Bone, 14: 19-27, 1993). Briefly, the fracture site is sawed 8 mm to both sides of the fracture line, embedded in methylmethacrylate so as not to demineralize, and the frontal section being 8 μm thick on a Reichert-Jung Polycut microtome. Cut. Masson-Trichrome stained frontal-center sections (including both tibia and fibula) are used to visualize cellular and tissue responses to fracture healing in the presence and absence of treatment. Sirius red stained sections are used to demonstrate the characteristics of the callus structure and to distinguish between lamella and lamellar bone at the fracture site. The following measurements are made: (1) fracture gap—measured at the shortest gap between the cortical end of the bone in the fracture, (2) the bone length and the pubic diameter, (3) the total bone volume area of the bone, ( 4) bone tissue per tissue area inside the bone area, (5) fibrous tissue in the bone, and (6) cartilage area in the bone.

생체역학적 분석: 생체역학적 분석을 위한 방법은 배크 (Bak) 및 안드레아센 (Andreassen)에 의해서 이미 공개되었다 (The Effects of Aging on Fracture Healing in Rats. Calcif Tissue Int 45:292-297, 1989). 간략하면, 생체역학적 시험 전에 모든 골절의 방사성사진을 찍는다. 치유 골절의 기계적 특성은 파괴성 3- 또는 4-점 벤딩방법에 의해서 분석한다. 최대 부하, 강성, 최대 부하에서의 에너지, 최대 부하에서의 편향, 및 최대 응력을 측정한다. Biomechanical Analysis : Methods for biomechanical analysis have already been published by Bak and Andreassen (The Effects of Aging on Fracture Healing in Rats.Calcif Tissue Int 45: 292-297, 1989). In brief, radiographs of all fractures are taken before biomechanical testing. Mechanical properties of healing fractures are analyzed by destructive 3- or 4-point bending methods. Maximum load, stiffness, energy at maximum load, deflection at maximum load, and maximum stress are measured.

(b) 국소 투여 후의 골절 치유에 대한 효과에 대한 시험(b) Test for effect on fracture healing after topical administration

골절 기술: 약 2년령의 암컷 및 수컷 비글 개를 시험에서 마취 하에 사용한다. 횡방사상 골절은 레니한 (Lenehan) 등에 의해서 기술된 바와 같이 3-점 벤딩에서 느리고 연속적인 부하를 줌으로써 생성시킨다 (Lenehan, T.M.; Balligand, M.; Nunamaker, D.M.; Wood, F.E.; Effects of EHDP on Fracture Healing in Dogs. J Orthop Res 3:499-507; 1985). 골절 부위를 통해서 와이어 (wire)를 잡아당겨서 뼈의 완전한 해부학적 붕괴를 보장한다. 그 후에, 골절 부위에 대한 프로스타글란딘 작용제의 국소적 송달은 서방성 펠릿에 의해 송달된 화합물의 느린 방출에 의해서, 또는 페이스트 겔 용액 또는 현탁액과 같은 적합한 제제로 화합물을 10, 15 또는 20주일 동안 투여함으로써 달성된다. Fracture technique : Female and male beagle dogs about 2 years of age are used under anesthesia in the trial. Lateral fractures are created by slow and continuous loading at three-point bending as described by Lenhan et al. (Lenehan, TM; Balligand, M .; Nunamaker, DM; Wood, FE; Effects of EHDP on Fracture Healing in Dogs.J Orthop Res 3: 499-507; 1985). The wire is pulled through the fracture site to ensure complete anatomical collapse of the bone. Thereafter, local delivery of the prostaglandin agonist to the fracture site may be achieved by slow release of the compound delivered by the sustained release pellet, or by administering the compound for 10, 15 or 20 weeks in a suitable formulation such as a paste gel solution or suspension. Is achieved.

조직학적 분석: 골절된 뼈의 조직학적 분석을 위한 방법은 피터 (Peter) 등 (Peter, C.P.; Cook, W.O.; Nunamaker, D.M.; Provost, M.T.; Seedor, J.G.; Rodan, G.A. Effects of alendronate on fracture healing and bone remodeling in dogs. J. Orthop. Res. 14:74-70, 1996) 및 모세킬드 (Mosekilde)와 배크 (Bak) (The Effects of Growth Hormone on Fracture Healing in Rats: A Histological Description. Bone, 14:19-27, 1993)에 의해서 이미 공개되었다. 간략하면, 치사시킨 후에 골절 부위를 골절선의 양쪽까지 3 ㎝를 톱질하고, 메틸메타크릴레이트 중에 포매하여 탈회되지 않게 하고, 라이허트-정 폴리컷트 마이크로톰 상에서 전두 절편을 8 ㎛ 두께로 절단한다. 치료의 존재 및 부재 하에서 골절 치유에 대한 세포성 및 조직 반응을 가시화시키기 위하여 매송-트리크롬 염색된 전두-중앙 절편 (경골 및 비골 둘 다를 포함)을 사용한다. 시리우스 레드 염색된 절편을 사용하여 가골구조의 특성을 입증하고, 골절 부위에서 무층골과 층상골 사이를 구분한다. 이하의 측정이 수행된다: (1) 골절 갭 - 골절에서 피질성 골말단 사이의 최단 간격으로 측정됨, (2) 가골 길이 및 기골 직경, (3) 가골의 총 골용적 면적, (4) 가골 영역 내부의 조직 면적당 뼈조직, (5) 가골 내의 섬유상 조직, 및 (6) 가골 내의 연골 면적. Histological analysis : Methods for histological analysis of fractured bones include Peter, CP; Cook, WO; Nunamaker, DM; Provost, MT; Seedor, JG; Rodan, GA Effects of alendronate on fracture healing and bone remodeling in dogs.J. Orthop.Res. 14: 74-70, 1996) and Mosekilde and Bak (The Effects of Growth Hormone on Fracture Healing in Rats: A Histological Description.Bone, 14 : 19-27, 1993). Briefly, the fracture site is sawed 3 cm to both sides of the fracture line after lethal, embedded in methylmethacrylate so as not to demineralize, and the frontal sections are cut to 8 μm thickness on a Reichert-coated polycut microtome. Maesong-Trichrome stained frontal-central sections (including both tibia and fibula) are used to visualize cellular and tissue responses to fracture healing in the presence and absence of treatment. Sirius red stained sections are used to demonstrate the characteristics of the callus structure and to distinguish between the stratum corneum and lamellar bone at the fracture site. The following measurements are made: (1) fracture gap—measured at the shortest distance between the cortical end of the bone in fracture, (2) bone length and bone diameter, (3) total bone volume area of the bone, (4) bone Bone tissue per area of tissue inside the area, (5) fibrous tissue in the bone, and (6) cartilage area in the bone.

생체역학적 분석: 생체역학적 분석을 위한 방법은 배크 (Bak) 및 안드레아센 (Andreassen) (The Effects of Aging on Fracture Healing in Rats. Calcif Tissue Int 45:292-297, 1989) 및 피터 (Peter) 등 (Peter, C.P.; Cook, W.O.; Nunamaker, D.M.; Provost, M.T.; Seedor, J.G.; Rodan, G.A. Effects of alendronate on fracture healing and bone remodeling in dogs. J. Orthop. Res. 14:74-70, 1996)에 의해서 이미 공개되었다. 간략하면, 생체역학적 시험 전에 모든 골절의 방사성사진을 찍는다. 치유 골절의 기계적 특성은 파괴성 3- 또는 4-점 벤딩방법에 의해 서 분석한다. 최대 부하, 강성, 최대 부하에서의 에너지, 최대 부하에서의 편향, 및 최대 응력을 측정한다. Biomechanical Analysis : Methods for biomechanical analysis include Bak and Andreassen (The Effects of Aging on Fracture Healing in Rats.Calcif Tissue Int 45: 292-297, 1989) and Peter et al. Peter, CP; Cook, WO; Nunamaker, DM; Provost, MT; Seedor, JG; Rodan, GA Effects of alendronate on fracture healing and bone remodeling in dogs.J. Orthop.Res. 14: 74-70, 1996). Has already been published. In brief, radiographs of all fractures are taken before biomechanical testing. The mechanical properties of the healing fractures are analyzed by destructive 3- or 4-point bending methods. Maximum load, stiffness, energy at maximum load, deflection at maximum load, and maximum stress are measured.

본 발명의 화합물 (이하에서는 "활성화합물(들)"이라 함)의 투여는 작용부위에 화합물을 송달할 수 있는 어떤 방법에 의해서도 이루어질 수 있다. 이들 방법에는 경구적 경로, 십이지장내 경로, 비경구적 주사 (정맥내, 피하, 근육내, 혈관내 또는 주입을 포함), 국소 및 직장 투여가 포함된다.Administration of the compounds of the present invention (hereinafter referred to as "active compound (s)") may be by any method capable of delivering the compound to the site of action. These methods include oral route, intraduodenal route, parenteral injection (including intravenous, subcutaneous, intramuscular, endovascular or infusion), topical and rectal administration.

투여되는 활성화합물의 양은 치료할 대상, 질환 또는 상태의 중증도, 투여의 비율, 화합물의 기질, 및 처방의 판단에 따라서 좌우될 것이다. 그러나, 유효 투약량은 단일 또는 분할용량으로 1일에 체중 ㎏당, 약 0.001 내지 약 100 ㎎, 바람직하게는 약 1 내지 약 35 ㎎/㎏/일의 범위이다. 70 ㎏ 인체의 경우에, 이것은 약 0.05 내지 약 7 g/일, 바람직하게는 약 0.2 내지 약 2.5 g/일에 해당한다. 일부의 경우에, 전술한 범위의 하한선 이하의 투약량 레벨이 더 적절할 수 있지만, 다른 경우에는 더 대용량이 어떤 유해한 부작용도 야기하지 않으면서 이용될 수 있지만, 단 이러한 대용량은 우선 하루 전체에 걸친 투여를 위해서 몇개의 소용량으로 분할된다.The amount of active compound administered will depend on the subject to be treated, the severity of the disease or condition, the rate of administration, the substrate of the compound, and the judgment of the prescription. However, effective dosages range from about 0.001 to about 100 mg, preferably about 1 to about 35 mg / kg / day, per kg body weight per day in single or divided doses. In the case of a 70 kg human body, this corresponds to about 0.05 to about 7 g / day, preferably about 0.2 to about 2.5 g / day. In some cases, dosage levels below the lower limit of the aforementioned ranges may be more appropriate, while in other cases larger doses may be used without causing any adverse side effects, provided that such a large dose is first used for administration throughout the day. It is divided into several small doses.

활성화합물은 유일한 치료법으로 사용될 수 있거나, 하나 또는 그 이상의 다른 항종양제, 예를 들어, 유사분열 억제제, 예를 들어, 빈블라스틴; 알킬화제, 예를 들어, 시스플라틴, 카르보플라틴 및 사이클로포스파마이드; 항대사물질, 예를 들어, 5-플루오로우라실, 사이토신 아라비노사이드 및 하이드록시우레아, 또는 예를 들어, N-(5-[N-(3,4-디하이드로-2-메틸-4-옥소퀴나졸린-6-일메틸)-N-메틸아미 노]-2-테노일)-L-글루탐산과 같은 유럽특허출원 제 239362 호에 기술된 바람직한 항대사물질 중의 하나; 성장인자 억제제; 세포주기 억제제; 삽입성 항생제, 예를 들어, 아드리아마이신 및 블레오마이신; 효소, 예를 들어, 인터페론; 및 항호르몬제, 예를 들어, 놀바덱스 (Nolvadex™; 타목시펜)과 같은 항에스트로겐제, 또는 예를 들어, 카소덱스 (Casodex™; (4'-시아노-3-(4-플루오로페닐설포닐)-2-하이드록시-2-메틸-3'-(트리플루오로메틸)프로피온아닐리드)와 같은 항안드로겐제로부터 선택된 항종양제를 포함할 수 있다. 이러한 공동치료는 치료의 각각의 성분을 동시, 연속 또는 별도로 투약하는 방법에 의해서 달성될 수 있다.The active compound may be used as the only treatment or may include one or more other antitumor agents, such as mitosis inhibitors such as vinblastine; Alkylating agents such as cisplatin, carboplatin and cyclophosphamide; Antimetabolites, for example 5-fluorouracil, cytosine arabinoside and hydroxyurea, or for example N- (5- [N- (3,4-dihydro-2-methyl-4 One of the preferred anti-metabolites described in European Patent Application No. 239362, such as -oxoquinazolin-6-ylmethyl) -N-methylamino] -2-tenoyl) -L-glutamic acid; Growth factor inhibitors; Cell cycle inhibitors; Intercalating antibiotics such as adriamycin and bleomycin; Enzymes such as interferon; And anti-hormonal agents such as antiestrogens such as Nolvadex ™, tamoxifen, or, for example, Casodex ™; (4′-cyano-3- (4-fluorophenylsul Anti-neoplastic agents selected from anti-androgens, such as polyvinyl) -2-hydroxy-2-methyl-3 '-(trifluoromethyl) propionanilide). It can be achieved by a simultaneous, continuous or separate dosing method.

약제학적 조성물은 예를 들어, 정제, 캅셀제, 환제, 분말, 서방성 제제, 용액, 현탁액으로서 경구 투여, 멸균 용액, 현탁액 또는 에멀전으로서 비경구용 주사, 연고제 또는 크림으로서 국소 투여, 또는 좌제로서 직장 투여하기에 적합한 형태일 수 있다. 약제학적 조성물은 정확한 투약량의 단일 투여에 적합한 단위 투약형일 수 있다. 약제학적 조성물은 통상적인 약제학적 담체 또는 부형제, 및 활성성분으로서 본 발명에 따르는 화합물을 포함할 수 있다. 또한, 이것은 그 밖의 다른 의학적 또는 약제학적 성분, 담체, 보조제 등을 포함할 수도 있다.Pharmaceutical compositions are, for example, oral administration as tablets, capsules, pills, powders, sustained release preparations, solutions, suspensions, parenteral injections as sterile solutions, suspensions or emulsions, topical administration as ointments or creams, or rectal administration as suppositories. It may be in a form suitable for the following. The pharmaceutical composition may be in unit dosage forms suitable for single administration of precise dosages. The pharmaceutical compositions may comprise conventional pharmaceutical carriers or excipients and the compounds according to the invention as active ingredients. It may also include other medical or pharmaceutical ingredients, carriers, adjuvants and the like.

비경구적 투여형태의 예로는 멸균 수용액, 예를 들어, 수성 프로필렌 글리콜 또는 덱스트로즈 용액 중의 활성화합물의 용액 또는 현탁액이 포함된다. 이러한 투약형은 적합하게는 필요에 따라서 완충될 수 있다.Examples of parenteral dosage forms include solutions or suspensions of the active compounds in sterile aqueous solutions such as aqueous propylene glycol or dextrose solutions. Such dosage forms may suitably be buffered as needed.

적합한 약제학적 담체는 불활성 희석제 또는 충진제, 물 및 다양한 유기용매를 포함한다. 약제학적 조성물은 필요한 경우에, 방향제, 결합제, 부형제 등과 같 은 추가의 성분들을 포함할 수 있다. 따라서, 경구 투여의 경우에는 시트르산과 같은 다양한 부형제를 함유하는 정제를 탈크, 알긴산 및 특정의 복합 실리케이트와 같은 다양한 붕해제 및 슈크로즈, 젤라틴 및 아카시아와 같은 결합제와 함께 사용될 수 있다. 또한, 마그네슘 스테아레이트, 나트륨 라우릴 설페이트 및 탈크와 같은 윤활제가 종종 정제화 목적에 유용하다. 유사한 타입의 고체 조성물은 또한, 연질 및 경질 충진된 젤라틴 캅셀제에서 사용될 수도 있다. 따라서, 바람직한 물질에는 락토즈 또는 유당 및 고분자량 폴리에틸렌 글리콜이 포함된다. 수용액 또는 엘릭서가 경구 투여에 바람직한 경우에, 그 안의 활성성분은 물, 에탄올, 프로필렌 글리콜, 글리세린 또는 이들의 배합물과 같은 희석제와 함께 다양한 감미제 또는 방향제, 착색제 또는 염료, 및 필요한 경우에 유화제 또는 현탁화제와 배합될 수 있다.Suitable pharmaceutical carriers include inert diluents or fillers, water and various organic solvents. The pharmaceutical composition may, if necessary, include additional ingredients such as fragrances, binders, excipients and the like. Thus, for oral administration, tablets containing various excipients such as citric acid can be used with various disintegrants such as talc, alginic acid and certain complex silicates and binders such as sucrose, gelatin and acacia. In addition, lubricants such as magnesium stearate, sodium lauryl sulfate and talc are often useful for tableting purposes. Solid compositions of a similar type may also be used in soft and hard filled gelatin capsules. Thus, preferred materials include lactose or lactose and high molecular weight polyethylene glycols. If aqueous solutions or elixirs are preferred for oral administration, the active ingredients therein are various sweetening or fragrances, colorants or dyes, and diluents such as water, ethanol, propylene glycol, glycerin or combinations thereof, and emulsifiers or suspending agents, if necessary. It can be combined with.

특정량의 활성화합물을 사용하여 다양한 약제학적 조성물을 제조하는 방법은 공지되어 있거나, 본 기술분야에서 숙련된 전문가에게 명백할 수 있을 것이다. 예를 들어, 문헌 (Remington's Pharmaceutical Sciences, Mack Publishing Company, Easter, Pa., 15th Edition (1975))을 참고로 한다.Methods of preparing various pharmaceutical compositions using specific amounts of active compounds are known or will be apparent to those skilled in the art. For example, Remington's Pharmaceutical Sciences , Mack Publishing Company, Easter, Pa., 15th Edition (1975).

이하에 제시된 실시예 및 제조예는 본 발명의 화합물 및 이러한 화합물을 제조하는 방법을 더 설명하고 예시하는 것이다. 본 발명의 범위는 이하의 실시예 및 제조예의 범위에 의해서 어떤 식으로든 제한되지 않는 것으로 이해되어야 한다. 이하의 실시예에서, 하나의 키랄 중심을 갖는 분자는 다른 식으로 언급되지 않는 한은 라세미 혼합물로서 존재한다. 두개 또는 그 이상의 키랄 중심을 갖는 이들 분자는 다른 식으로 언급되지 않는 한은 부분입체이성체의 라세미 혼합물로서 존재한다. 단일 에난티오머/부분입체이성체는 본 기술분야에서 숙련된 전문가에게 공지된 방법에 의해서 수득될 수 있다.The examples and preparations set forth below further illustrate and illustrate the compounds of the present invention and methods of making such compounds. It is to be understood that the scope of the present invention is not limited in any way by the scope of the following examples and preparations. In the examples below, molecules with one chiral center are present as racemic mixtures unless stated otherwise. These molecules with two or more chiral centers exist as racemic mixtures of diastereomers unless otherwise stated. Single enantiomers / diastereomers may be obtained by methods known to those skilled in the art.

이하의 제조예 및 실시예에서 HPLC 크로마토그라피가 언급되는 경우에, 사용되는 일반적인 조건은 다른 식으로 지시되지 않는 한은 다음과 같다. 사용된 칼럼은 150 ㎜ 거리 및 4.6 ㎜ 내경을 갖는 조르박스 (ZORVAX™) RXC18 칼럼 (Hewlett Packard에 의해서 제조됨)이다. 샘플은 휴렛 패카드 (Hewlett Packard)-1100 시스템 상에서 주행시킨다. 10분에 걸쳐서 100％ 암모늄 아세테이트/아세트산 완충액 (0.2 M)에서 100％ 아세토니트릴까지 주행하는 구배 용매방법이 사용된다. 그 후, 시스템은 1.5분 동안 100％ 아세토니트릴, 및 그 다음에 3분 동안 100％ 완충용액을 사용하는 세척 사이클을 진행시킨다. 이 기간에 걸친 유속은 일정한 3 ㎖/분이다.Where HPLC chromatography is mentioned in the preparations and examples below, the general conditions used are as follows unless otherwise indicated. The column used is a ZORVAX ™ RXC18 column (manufactured by Hewlett Packard) with a 150 mm distance and a 4.6 mm inner diameter. Samples are run on a Hewlett Packard-1100 system. A gradient solvent method is used which runs from 100% ammonium acetate / acetic acid buffer (0.2 M) to 100% acetonitrile over 10 minutes. The system then runs a wash cycle using 100% acetonitrile for 1.5 minutes and then 100% buffer for 3 minutes. The flow rate over this period is a constant 3 ml / min.

일반적 방법General method

5-니트로-5-nitro- 옥스인돌의Oxindole 제조: Produce:

-15℃에서 100 ㎖ 진환 황산 중의 옥스인돌 (26 g)의 용액에 발현 질산 (8.4 ㎖)을 적가하였다. 반응온도가 -15℃에서 유지되도록 조심스러운 주의를 기울였다. 첨가가 완료된 후에, 반응액을 30분 동안 교반한 다음, 얼음물에 부었다. 황색 침전이 형성되었으며, 이것을 여과에 의해 분리하여 34 g (98％)의 5-니트로 옥 스인돌을 제공하였다.Expressed nitric acid (8.4 mL) was added dropwise to a solution of oxindole (26 g) in 100 mL cyclohexane sulfuric acid at -15 ° C. Careful care was taken to keep the reaction temperature at -15 ° C. After the addition was completed, the reaction solution was stirred for 30 minutes and then poured into ice water. A yellow precipitate formed which was separated by filtration to give 34 g (98%) of 5-nitro oxindole.

5-아미노-5-amino- 옥스인돌Oxindole (2)의 제조: (2) Manufacture of:

파르 병 (Parr bottle) 내에서 120 ㎖의 디메틸아세트아미드 중의 5-니트로-옥스인돌 (25 g)의 용액에 10％ Pd/C (0.5 g)를 첨가하였다. 혼합물을 16시간 동안 수소화시켰다 (40 psi H2). 촉매를 여과에 의해서 제거하고, 여액을 에테르 (2 L)로 희석하여 5-아미노-옥스인돌 (10.5 g; 50％)을 제공하였다.To a solution of 5-nitro-oxindole (25 g) in 120 mL dimethylacetamide in a Parr bottle was added 10% Pd / C (0.5 g). The mixture was hydrogenated for 16 hours (40 psi H 2 ). The catalyst was removed by filtration and the filtrate was diluted with ether (2 L) to give 5-amino-oxindole (10.5 g; 50%).

2,4-2,4- 디클로로Dichloro -5--5- 트리플루오로메틸피리미딘의Of trifluoromethylpyrimidine 제조 (3): Manufacture (3):

5-트리플루오로메틸우라실 (250 g, 1.39 mol) 및 옥시염화인 (655 ㎖, 6.94 mol, 5 당량)을 오버헤드 교반기 (overhead stirrer), 환류냉각기, 첨가 깔때기 및 내부 열전기쌍이 장치된 3 L 4-구 플라스크에 충전하였다. 내용물을 질소 대기 하에서 유지시키면서 진한 인산 (85 wt％, 9.5 ㎖, 0.1 당량)을 슬러리에 한꺼번에 첨가하여 중등도의 발열을 야기시켰다. 그 후, 디이소프로필에틸아민 (245 ㎖, 1.39 mol, 1 당량)을 반응액의 내부 온도가 첨가의 말기까지 85-90℃에 도달하도록 하는 속도로 15분에 걸쳐서 적가하였다. 아민 첨가가 끝나면, 반응혼합물은 균질의 밝은 오렌지색 용액이었다. 가열을 개시하였으며, 오렌지색 용액을 20시간 동안 100℃에서 유지시켰으며, 이 시간에 반응혼합물의 HPLC 분석은 출발물질이 소비되었음을 나타내었다. 외부 가열을 제거하고, 플라스크의 내용물을 40℃로 냉각시킨 다음에 켄치 포트 (quench pot)의 온도를 10℃와 15℃ 사이에서 유지시키면서 3 N HCl (5 L, 10 당량) 및 디에틸 에테르 (2 L)의 냉각 혼합물에 적가하였다. 층을 분리시키고, 수층을 에테르 (1 L)로 1 회 추출하였다. 유기층을 합하고, 세척액이 중성이 될 때까지 (5×1.5 L 세척) 물로 세척하고, MgSO4로 건조시키고, 농축하여 순도 96％ (HPLC)의 밝은 황색-오렌지색 오일 288 g (95％ 수율)을 제공하였다. 이 물질을 증류 (79 mmHg에서 bp 109℃)시켜 더 정제하였다.5-trifluoromethyluracil (250 g, 1.39 mol) and phosphorus oxychloride (655 mL, 6.94 mol, 5 equiv) were charged with 3 L equipped with an overhead stirrer, reflux cooler, addition funnel and internal thermocouple Filled into a four-necked flask. Concentrated phosphoric acid (85 wt%, 9.5 mL, 0.1 equiv) was added to the slurry all at once while maintaining the contents under a nitrogen atmosphere, resulting in moderate exotherm. Thereafter, diisopropylethylamine (245 mL, 1.39 mol, 1 equiv) was added dropwise over 15 minutes at a rate such that the internal temperature of the reaction solution reached 85-90 ° C until the end of the addition. After the addition of the amine, the reaction mixture was a homogeneous bright orange solution. Heating was initiated and the orange solution was kept at 100 ° C. for 20 hours, at which time HPLC analysis of the reaction mixture showed that the starting material was consumed. External heating was removed, the contents of the flask was cooled to 40 ° C. and then 3 N HCl (5 L, 10 equiv) and diethyl ether (while maintaining the temperature of the quench pot between 10 ° C. and 15 ° C. 2 L) was added dropwise to the cooling mixture. The layers were separated and the aqueous layer was extracted once with ether (1 L). The organic layers were combined, washed with water until the wash was neutral (wash 5 × 1.5 L), dried over MgSO 4 and concentrated to give 288 g (95% yield) of a light yellow-orange oil of 96% purity (HPLC). Provided. This material was further purified by distillation (bp 109 ° C. at 79 mmHg).

5-(4-5- (4- 클로로Chloro -5--5- 트리플루오로메틸Trifluoromethyl -피리미딘-2--Pyrimidine-2- 일아미노Monoamino )-1,3-) -1,3- 디하이드로Dehydro -인돌-2-온 (4)의 제조:Preparation of Indole-2-one (4):

1:1 DCE/tBuOH (1.240 L) 중의 5-트리플루오로메틸-2,4-디클로로피리미딘 (214.8 g; 0.921 mol)의 용액에 에테르 중의 염화아연 1 M 용액 (1 당량; 0.921 L)을 첨가하였다. 0.5 시간 후에, 5-아미노-옥스인돌 (124 g; 0.837 mol)을 첨가하고, 이어서 온도를 25℃에서 유지시키면서 트리에틸아민 (129.4 ㎖; 0.921 mol)을 첨가하였다. 반응액을 실온에서 밤새 교반한 다음에 농축시키고, 생성물을 황색 고체 (224.3 g; 82％)로서 메탄올로부터 연마하였다. 1H NMR (DMSO-d6, 400 MHz) δ 3.29 (s, 2H), 6.76 (d, J= 7.9 Hz, 2H), 7.39 (d, J= 8.3 Hz), 7.51 (br s, 1H), 8.71 (s, 1H), 10.33 (s, 1H), 10.49 (s, 1H). 13C NMR (DMSO-d6, 100 MHz) δ 177.0, 161.3, 158.7 (br), 140.7, 132.8, 126.9, 123.7 (q, J= 268 Hz), 121.0, 118.7, 111.2 (q, J= 32 Hz), 109.6, 36.7; HPLC 체류시간: 5.759분. LRMS (M+) 329.1, 331.1.To a solution of 5-trifluoromethyl-2,4-dichloropyrimidine (214.8 g; 0.921 mol) in 1: 1 DCE / tBuOH (1.240 L) was added a 1M solution of zinc chloride in ether (1 equivalent; 0.921 L). Added. After 0.5 h, 5-amino-oxindole (124 g; 0.837 mol) was added, followed by triethylamine (129.4 mL; 0.921 mol) while maintaining the temperature at 25 ° C. The reaction was stirred at rt overnight then concentrated and the product was triturated from methanol as a yellow solid (224.3 g; 82%). 1 H NMR (DMSO-d 6 , 400 MHz) δ 3.29 (s, 2H), 6.76 (d, J = 7.9 Hz, 2H), 7.39 (d, J = 8.3 Hz), 7.51 (br s, 1H), 8.71 (s, 1 H), 10.33 (s, 1 H), 10.49 (s, 1 H). 13 C NMR (DMSO-d 6 , 100 MHz) δ 177.0, 161.3, 158.7 (br), 140.7, 132.8, 126.9, 123.7 (q, J = 268 Hz), 121.0, 118.7, 111.2 (q, J = 32 Hz ), 109.6, 36.7; HPLC retention time: 5.759 min. LRMS (M &lt; + &gt;) 329.1, 331.1.

실시예Example 1 One

5-[4-(R-1-5- [4- (R-1- 페닐Phenyl -- 에틸아미노Ethylamino )-5-) -5- 트리플루오로메틸Trifluoromethyl -피리미딘-2--Pyrimidine-2- 일아미노Monoamino ]-1,3-] -1,3- 디하이드로Dehydro -인돌-2-온Indole-2-one

Figure 112006082893189-PCT00024
Figure 112006082893189-PCT00024

1:1 DCE/t-BuOH 알콜 (1:1 비, 4 ㎖) 및 5-(4-클로로-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온 (0.15 g; 0.456 mmole)의 용액에 (R)(+) 알파 펜에틸 아민 (0.071 ㎖; 0.547 mmole) 및 디이소프로필 에틸 아민 (0.081 ㎖, 0.456 mmole)을 첨가하였다. 생성된 용액을 질소 하에서 교반하고, 16시간 동안 80℃로 가열하였다. 반응액을 실온으로 냉각시키고, ~10 ㎖의 디클로로메탄과 메탄올의 1:1 혼합물로 희석하고, 이어서 0.5 g의 MP-카보네이트를 첨가하였다. 생성된 혼합물을 교반하고, 여과하여, 농축시키고, 실리카겔 크로마토그라피 (클로로메탄/메탄올/진한 수산화암모늄의 97:2.8:0.3 비)에 의해서 정제하였다. 목적하는 표제화합물은 백색 고체 (0.021 g; 11％)로서 수득하였다. HPLC 체류시간: 6.46분. LRMS (M+) 413.4.1: 1 DCE / t-BuOH alcohol (1: 1 ratio, 4 mL) and 5- (4-chloro-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indole To a solution of 2-one (0.15 g; 0.456 mmole) was added (R) (+) alpha phenethyl amine (0.071 mL; 0.547 mmole) and diisopropyl ethyl amine (0.081 mL, 0.456 mmole). The resulting solution was stirred under nitrogen and heated to 80 ° C. for 16 h. The reaction was cooled to room temperature, diluted with ˜10 mL of a 1: 1 mixture of dichloromethane and methanol, followed by addition of 0.5 g MP-carbonate. The resulting mixture was stirred, filtered, concentrated and purified by silica gel chromatography (97: 2.8: 0.3 ratio of chloromethane / methanol / condensed ammonium hydroxide). The desired title compound was obtained as a white solid (0.021 g; 11%). HPLC retention time: 6.46 min. LRMS (M &lt; + &gt;) 413.4.

이하의 본 발명의 화합물은 실시예 1에서와 같이 클로로피리미딘 (4)과 적절한 아민을 가열함으로써 제조되었다. 이들 반응에서 사용된 아민은 시판품으로 수득하여 공급받은 대로 사용하거나, 또는 이들은 본 기술분야에서 숙련된 전문가에게 공지된 아민에 대한 통상적인 합성방법에 의해서 제조되었다. 다른 식으로 언 급되지 않는 한, 키랄 중심을 갖는 화합물은 라세미 혼합물로 제조되었다.The following compounds of the present invention were prepared by heating chloropyrimidine (4) and appropriate amines as in Example 1. The amines used in these reactions were obtained as commercially available products or used as supplied, or they were prepared by conventional synthetic methods for amines known to those skilled in the art. Unless stated otherwise, compounds with chiral centers were prepared in racemic mixtures.

실시예 1의 방법에 의해서 제조된 화합물Compounds Prepared By The Method Of Example 1 화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) N-(1-메틸-1-페닐-에틸)-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤젠설폰아미드N- (1-Methyl-1-phenyl-ethyl) -3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyri Midin-4-ylamino] -methyl} -benzenesulfonamide 6.466.46 597.5597.5 3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤젠설폰아미드3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -benzenesulfonamide 4.874.87 479.1479.1 5-{4-[3-(트리플루오로-메탄설포닐)-벤질아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [3- (trifluoro-methanesulfonyl) -benzylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 6.356.35 532.1532.1 5-{4-[(피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 3.743.74 407.3407.3 5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.215.21 485.2485.2 N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl) -methanesulfonamide 5.225.22 493.3493.3 3-옥소-3-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피페리딘-1-일)-프로피오니트릴3-oxo-3- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -piperidin-1-yl) -propionitrile 4.924.92 474.3474.3 5-{4-[3-(1,1-디옥소-1N6-이소티아졸리딘-2-일)-프로필아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [3- (1,1-Dioxo-1N 6 -isothiazolidin-2-yl) -propylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1 , 3-dihydro-indol-2-one 4.894.89 471.1471.1 5-[4-(2-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-Methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.536.53 380.3380.3 5-{4-[(1-메탄설포닐-피페리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-piperidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.175.17 485.3485.3 N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl} -methane Sulfonamide 4.384.38 431.2431.2 N-{4-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-부틸}-메탄설폰아미드N- {4- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -butyl} -methane Sulfonamide 4.784.78 459.3459.3 5-{4-[(1-메탄설포닐-피페리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-piperidin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.225.22 485.3485.3 N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -methanesulfonamide 4.814.81 445.1445.1 메탄설폰산 3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐 에스테르Methanesulfonic acid 3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl ester 5.675.67 494.1494.1 N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드N- {3- [2- (2-Oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl} -methane Sulfonamide 4.584.58 445.1445.1

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[(4-메탄설포닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-Methanesulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 4.874.87 487.2487.2 N-(4-플루오로-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (4-Fluoro-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide 5.295.29 511.1511.1 5-{4-[(5-옥소-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(5-oxo-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On 4.124.12 423.3423.3 N-(4-메톡시-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (4-methoxy-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide 5.385.38 523.2523.2 N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 5.305.30 507.2507.2 5-[4-(3-메탄설포닐메틸-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.145.14 492.2492.2 5-{4-[(4-트리플루오로아세틸-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-trifluoroacetyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.645.64 505.1505.1 5-{4-[(1-메탄설포닐-아제티딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-azetidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 4.764.76 457.2457.2 N-메틸-N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-methyl-N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide 6.666.66 521.3521.3 5-{4-[(1-메탄설포닐-피롤리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-pyrrolidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 4.974.97 471.2471.2 N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -methanesulfonamide 5.025.02 459.2459.2 5-{4-[2-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노]-프로필}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino] -propyl} -1,3 -Dihydro-indol-2-one 5.715.71 499.4499.4 5-{4-[(4-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 4.684.68 479.1479.1 {2,2-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-카밤산 tert-부틸 에스테르{2,2-Dimethyl-3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -carbamic acid tert-butyl ester 7.017.01 495.0495.0 5-[4-(3-이소프로폭시-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-isopropoxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.276.27 410.4410.4 5-{4-[(1-메틸-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 3.713.71 421.0421.0 5-{4-[(테트라하이드로-피란-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(tetrahydro-pyran-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.165.16 408.3408.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-[4-(2-에틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-ethyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.956.95 394.3394.3 5-{4-[(테트라하이드로-푸란-2R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(tetrahydro-furan-2R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.305.30 394.3394.3 5-{4-[(테트라하이드로-푸란-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(tetrahydro-furan-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.305.30 394.3394.3 5-{4-[(5-메틸-푸란-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(5-methyl-furan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.985.98 404.2404.2 5-{4-[(1-메탄설포닐-피롤리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-pyrrolidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 508508 471.3471.3 5-{4-[(아다만탄-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(adamantan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 7.897.89 458.3458.3 5-{4-[(아다만탄-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(adamantan-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.205.20 473.3473.3 5-[4-(2-메톡시-2-메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-methoxy-2-methyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.875.87 396.3396.3 5-{4-[(엔도-비사이클로[2.2.1]헵트-5-엔-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(endo-bicyclo [2.2.1] hept-5-en-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indol-2-one 6.746.74 416.3416.3 (3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-벤질)-포스폰산 디메틸 에스테르(3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -benzyl) -Phosphonic acid dimethyl ester 5.035.03 522.2522.2 5-[4-(3-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-Methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.876.87 380.2380.2 5-{4-[(2-하이드록시-사이클로헥실메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(2-hydroxycyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one 6.666.66 422.2422.2 N-(4-메톡시-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드N- (4-methoxy-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide 5.695.69 537.2537.2 5-{4-[(4-에탄설포닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-ethanesulfonyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 5.115.11 501.3501.3 5-(4-{[4-(프로판-2-설포닐)-모르폴린-2-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-{[4- (Propan-2-sulfonyl) -morpholin-2-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino) -1,3- Dihydro-indol-2-one 5.355.35 515.2515.2 5-{4-[(4-아세틸-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-acetyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On 4.434.43 451.2451.2 5-{4-[(4-프로피오닐-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-propionyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 4.744.74 465.2465.2

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-(4-{[4-(2,2-디메틸-프로피오닐)-모르폴린-2-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-{[4- (2,2-dimethyl-propionyl) -morpholin-2-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino) -1, 3-dihydro-indol-2-one 5.435.43 493.2493.2 2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-모르폴린-4-카복실산 메틸 에스테르2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -morpholine- 4-carboxylic acid methyl ester 5.045.04 467.2467.2 5-{4-[(4-메톡시아세틸-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-methoxyacetyl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 4.444.44 481.2481.2 5-[4-(3-에탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-ethanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.365.36 492.3492.3 5-{4-[(4-메탄설포닐-모르폴린-2R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-Methanesulfonyl-morpholine-2R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 4.844.84 487.3487.3 5-{4-[(4-메탄설포닐-모르폴린-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-Methanesulfonyl-morpholin-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 4.864.86 487.3487.3 5-{4-[(피리미딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(pyrimidin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 4.534.53 402.3402.3 5-{4-[(피라진-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(pyrazin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 4.424.42 402.1402.1 N-(4-플루오로-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드N- (4-Fluoro-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide 5.555.55 523.3523.3 5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.175.17 485.3485.3 5-{4-[(4-이소부티릴-모르폴린-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-isobutyryl-morpholin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 5.035.03 479.2479.2 5-[4-(3,3-디메틸-2-옥소-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3,3-dimethyl-2-oxo-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.006.00 408.2408.2 5-[4-(1,2-디메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1,2-Dimethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.656.65 380.3380.3 5-[4-(2-메톡시-1-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-methoxy-1-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.575.57 382.3382.3 5-{4-[2-(1,1-디옥소-1D6-이소티아졸리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1,1-Dioxo-1D 6 -isothiazolidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1 , 3-dihydro-indol-2-one 4.594.59 457.3457.3 5-[4-(3-메틸아미노-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-methylamino-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 3.473.47 381.3381.3 5-{4-[(피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 4.624.62 401.3401.3 5-{4-[(6-메탄설포닐-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(6-Methanesulfonyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 4.894.89 479.3479.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[3-(1,1-디옥소-1,1,6-이소티아졸리딘-2-일)-벤질아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [3- (1,1-Dioxo-1,1,6-isothiazolidin-2-yl) -benzylamino] -5-trifluoromethyl-pyrimidin-2-ylamino } -1,3-dihydro-indol-2-one 5.455.45 519.2519.2 5-[4-(1R-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1R-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.426.42 414.4414.4 5-(4-이소프로필아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-isopropylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 5.845.84 352.2352.2 5-(4R-sec-부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4R-sec-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.226.22 366.2366.2 5-(4S-sec-부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4S-sec-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.236.23 366.2366.2 5-[4-(2-메틸아미노-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-Methylamino-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1, 3-dihydro-indol-2-one 3.293.29 367.3367.3 5-[4-(1S-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1S-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.426.42 414.3414.3 5-{4-[(2-메탄설포닐메틸-티아졸-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(2-methanesulfonylmethyl-thiazol-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 4.724.72 499.3499.3 5-(4-프로필아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-propylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 5.915.91 352.2352.2 5-[4-(2-하이드록시-1-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-hydroxy-1-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.494.49 368.2368.2 5-[4-(1-하이드록시메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.854.85 382.2382.2 5-{4-[(5-메탄설포닐-피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(5-methanesulfonyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 4.554.55 479.4479.4 5-{4-[(피리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(pyridin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 4.494.49 401.2401.2 5-[4-(1,3-디메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1,3-Dimethyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.996.99 394.3394.3 N-이소프로필-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드N-isopropyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Propyl} -methanesulfonamide 5.125.12 487.3487.3 5-[4-(1S-하이드록시메틸-2-메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1S-hydroxymethyl-2-methyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.235.23 396.3396.3 N-사이클로헥실-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드N-cyclohexyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Propyl} -methanesulfonamide 6.246.24 527.2527.2 5-[4-(1,2,3,4-테트라하이드로-나프탈렌-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1,2,3,4-tetrahydro-naphthalen-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole- 2-on 440.4440.4 7.177.17 5-{4-[(1-메탄설포닐-피롤리딘-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-pyrrolidin-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.075.07 471.2471.2 5-{4-[(3-메틸-티오펜-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(3-methyl-thiophen-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On 6.186.18 420.4420.4

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[(1-메탄설포닐-피롤리딘-3R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-pyrrolidin-3R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 4.954.95 471.2471.2 5-[4-(2-하이드록시-1S-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-hydroxy-1S-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.285.28 430.3430.3 5-[4-(2-하이드록시-1S-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-hydroxy-1S-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.494.49 368.3368.3 5-[4-(1R-하이드록시메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1R-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.854.85 382.2382.2 5-[4-(1-피리미딘-4-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1-pyrimidin-4-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.844.84 416.3416.3 5-[4-(1,1-디옥소-테트라하이드로-1-티오펜-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1,1-Dioxo-tetrahydro-1-thiophen-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro- Indole-2-one 4.674.67 426.3426.3 5-{4-[(1H-이미다졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1H-imidazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 3.273.27 390.3390.3 5-[4-(2-피페리딘-2-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-piperidin-2-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 3.793.79 421.4421.4 5-[4-(이소부틸-메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (isobutyl-methyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1, 3-dihydro-indol-2-one 6.826.82 380.3380.3 N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 5.495.49 507.4507.4 N-에틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-ethyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 5.675.67 521.3521.3 5-[4-(2-메탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.475.47 478.2478.2 N-이소프로필-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-isopropyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide 5.815.81 535.3535.3 5-{4-[(3,4,5,6-테트라하이드로-2H-[1,2']비피리디닐-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidine-2 -Ylamino} -1,3-dihydro-indol-2-one 5.795.79 484.3484.3 5-{4-[(1-피리미딘-2-일-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-pyrimidin-2-yl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 6.176.17 485.3485.3 5-{4-[2R-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2R- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one 5.705.70 499.4499.4 5-{4-[2S-(1-메탄설포닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2S- (1-Methanesulfonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one 5.705.70 499.4499.4

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-[4-(3-메틸설파닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-methylsulfanyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.835.83 398.2398.2 5-[4-(1S-하이드록시메틸-3-메틸설파닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1S-hydroxymethyl-3-methylsulfanyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.025.02 428.2428.2 5-[4-(2-하이드록시-1R-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-hydroxy-1R-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.494.49 368.3368.3 5-[4-(1R-하이드록시메틸-2-메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1R-hydroxymethyl-2-methyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.235.23 396.4396.4 N-에틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드N-ethyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -methanesulfonamide 5.315.31 473.3473.3 5-{4-[(1-메탄설포닐-피롤리딘-3R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-pyrrolidin-3R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 4.944.94 471.4471.4 5-[4-(1S-하이드록시메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1S-hydroxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.864.86 382.3382.3 5-[4-(3,5-디니트로-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3,5-Dinitro-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.046.04 490.1490.1 N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl}- Phenyl) -methanesulfonamide 5.845.84 493.1493.1 N-이소프로필-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드N-isopropyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Ethyl} -methanesulfonamide 5.375.37 473.3473.3 5-[4-(2-하이드록시-1-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-hydroxy-1-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.295.29 430.3430.3 5-[4-(1R-하이드록시메틸-3-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1R-hydroxymethyl-3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.595.59 410.4410.4 5-[4-(1S-하이드록시메틸-3-메틸-부틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1S-hydroxymethyl-3-methyl-butylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.595.59 410.4410.4 5-{4-[(1-메탄설포닐-피페리딘-2S-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-piperidin-2S-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.165.16 485.3485.3 5-{4-[(1-메탄설포닐-피롤리딘-2R-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-pyrrolidin-2R-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.085.08 471.3471.3 5-[4-(메틸-피리딘-2-일메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (methyl-pyridin-2-ylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.375.37 415.3415.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[(3-메탄설포닐-벤질)-메틸-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(3-Methanesulfonyl-benzyl) -methyl-amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.665.66 492.3492.3 N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 5.635.63 507.3507.3 5-[4-(메틸-피리딘-3-일메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (Methyl-pyridin-3-ylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.255.25 415.4415.4 5-{4-[(1-메탄설포닐-피페리딘-3-일메틸)-메틸-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methanesulfonyl-piperidin-3-ylmethyl) -methyl-amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one 5.695.69 499.4499.4 5-[4-(메틸-피리딘-4-일메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (methyl-pyridin-4-ylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1, 3-dihydro-indol-2-one 5.125.12 415.3415.3 5-(4-사이클로펜틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-cyclopentylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.476.47 378.3378.3 5-[4-(2,6-디메톡시-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2,6-dimethoxy-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.786.78 460.3460.3 5-{4-[(1,5-디메틸-1H-피라졸-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1,5-Dimethyl-1H-pyrazol-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indole-2-one 4.994.99 418.3418.3 5-[4-(2-이미다졸-1-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-imidazol-1-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 3.583.58 404.2404.2 5-{4-[(피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 4.954.95 401.4401.4 5-[5-트리플루오로메틸-4-(2-트리플루오로메틸-벤질아미노)-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [5-Trifluoromethyl-4- (2-trifluoromethyl-benzylamino) -pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.576.57 468.2468.2 5-{4-[(3-메틸-피리딘-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(3-methyl-pyridin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 6.076.07 415.3415.3 5-[4-(3-메탄설포닐-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-methanesulfonyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.165.16 478.2478.2 5-{4-[2-(1-아세틸-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-acetyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.225.22 463.4463.4 5-{4-[2-(1-프로피오닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-propionyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indole-2-one 5.655.65 477.4477.4 5-{4-[2-(1-사이클로프로판카보닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-cyclopropanecarbonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 5.865.86 489.4489.4 5-{4-[2-(1-이소부티릴-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-Isobutyryl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one 6.076.07 491.3491.3 5-{4-[2-(1-부티릴-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-Butyryl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indole-2-one 5.995.99 491.4491.4 5-{4-[2-(1-메톡시아세틸-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-methoxyacetyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one 5.195.19 493.4493.4

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[2-(1-사이클로부탄카보닐-피페리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-cyclobutanecarbonyl-piperidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 6.316.31 503.4503.4 N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아세트아미드N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -acetamide 4.474.47 423.3423.3 N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-프로피온아미드N-Methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) 5-trifluoromethyl-pyrimidin-4-ylamino] -propyl } -Propionamide 4.894.89 437.45437.45 사이클로프로판카복실산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Cyclopropanecarboxylic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl }-amides 5.075.07 449.3449.3 N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-이소부티르아미드N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -isobutyramide 5.245.24 451.3451.3 N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-부티르아미드N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -butyramide 5.255.25 451.4451.4 2-메톡시-N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아세트아미드2-methoxy-N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -propyl} -acetamide 4.474.47 453.3453.3 사이클로부탄카복실산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Cyclobutanecarboxylic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl }-amides 5.485.48 463.4463.4 2,2,N-트리메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-프로피온아미드2,2, N-trimethyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -propyl} -propionamide 5.805.80 465.3465.3 2,N-디메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-부티르아미드2, N-dimethyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -butyramide 5.555.55 465.3465.3 N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-벤즈아미드N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -benzamide 5.385.38 485.3485.3 이속사졸-5-카복실산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Isoxazole-5-carboxylic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -amide 4.914.91 476.2476.2 모르폴린-4-카복실산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Morpholin-4-carboxylic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -amide 4.784.78 494.3494.3 에탄설폰산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Methyl ethanesulfonic acid- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl }-amides 5.295.29 473.3473.3 프로판-1-설폰산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Propane-1-sulfonic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -amide 5.715.71 487.3487.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 1,1,3-트리메틸-3-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-설포닐우레아1,1,3-trimethyl-3- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -propyl} -sulfonylurea 5.535.53 488.3488.3 2,2,2-트리플루오로-N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아세트아미드2,2,2-trifluoro-N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl -Pyrimidin-4-ylamino] -propyl} -acetamide 5.805.80 477.2477.2 N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아세트아미드N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -acetamide 4.234.23 409.2409.2 N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-프로피온아미드N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -propionamide 4.614.61 423.2423.2 사이클로프로판카복실산 메틸-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드Cyclopropanecarboxylic acid methyl- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl }-amides 4.774.77 435.2435.2 N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-이소부티르아미드N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -isobutyramide 4.944.94 437.2437.2 N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-부티르아미드N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -butyramide 4.954.95 437.2437.2 2-메톡시-N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아세트아미드2-methoxy-N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -ethyl} -acetamide 4.214.21 439.2439.2 사이클로부탄카복실산 메틸-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드Cyclobutanecarboxylic acid methyl- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl }-amides 5.175.17 449.3449.3 2,2,N-트리메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-프로피온아미드2,2, N-trimethyl-N- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -ethyl} -propionamide 5.575.57 451.4451.4 2,N-디메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-부티르아미드2, N-dimethyl-N- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -butyramide 5.265.26 451.4451.4 N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-벤즈아미드N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -benzamide 4.804.80 471.3471.3 이속사졸-5-카복실산 메틸-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드Isoxazole-5-carboxylic acid methyl- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -amide 4.514.51 462.3462.3 모르폴린-4-카복실산 메틸-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드Morpholin-4-carboxylic acid methyl- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -amide 4.414.41 480.3480.3 N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Ethyl} -methanesulfonamide 4.774.77 445.1445.1 에탄설폰산 메틸-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드Methyl ethanesulfonic acid- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl }-amides 5.035.03 459.2459.2

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 프로판-1-설폰산 메틸-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드Propane-1-sulfonic acid methyl- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -amide 5.445.44 473.3473.3 1,1,3-트리메틸-3-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-설포닐우레아1,1,3-trimethyl-3- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -ethyl} -sulfonylurea 5.495.49 474.2474.2 2,2,2-트리플루오로-N-메틸-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아세트아미드2,2,2-trifluoro-N-methyl-N- {2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl -Pyrimidin-4-ylamino] -ethyl} -acetamide 5.495.49 463.2463.2 5-[4-(2-하이드록시-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-hydroxy-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.054.05 354.3354.3 5-(4-사이클로프로필아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-cyclopropylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 5.415.41 350.3350.3 5-(4-사이클로부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-cyclobutylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.016.01 364.3364.3 5-[4-(1,4-디메틸-펜틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1,4-Dimethyl-pentylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 7.457.45 408.4408.4 5-[4-(3-이미다졸-1-일-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-imidazol-1-yl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 3.773.77 418.3418.3 5-[4-(2-페녹시-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-phenoxy-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.346.34 430.3430.3 5-[4-(1-사이클로헥실-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1-cyclohexyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 7.617.61 420.4420.4 5-[4-(1-하이드록시메틸-2,2-디메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1-hydroxymethyl-2,2-dimethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.645.64 410.4410.4 5-[4-(1-메톡시메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1-methoxymethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.965.96 396.3396.3 5-[4-(인단-2-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (Indan-2-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.786.78 426.4426.4 5-[4-(1,2,3,4-테트라하이드로-나프탈렌-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1,2,3,4-tetrahydro-naphthalen-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole- 2-on 7.167.16 440.3440.3 5-(4-사이클로헵틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-cycloheptylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 7.217.21 406.3406.3 5-{4-[2-(2-옥소-이미다졸리딘-1-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (2-oxo-imidazolidin-1-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indole-2-one 4.044.04 422.3422.3 4-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-부티르산 에틸 에스테르4- [2- (2-Oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -butyric acid ethyl ester 5.655.65 424.2424.2 5-[4-(2-하이드록시-1-하이드록시메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-hydroxy-1-hydroxymethyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 3.723.72 384.2384.2 5-[4-(3-하이드록시-2,2-디메틸-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-hydroxy-2,2-dimethyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.095.09 396.3396.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[(이소크로만-1-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(isochromen-1-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 6.366.36 456.3456.3 5-[4-(4-하이드록시-1,1-디옥소-테트라하이드로-1&-티오펜-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (4-hydroxy-1,1-dioxo-tetrahydro-1 & -thiophen-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1, 3-dihydro-indol-2-one 4.424.42 442.2442.2 5-[4-(2-메톡시-1-메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-methoxy-1-methyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.585.58 382.3382.3 5-[(트랜스-4-메틸설파닐-테트라하이드로-푸란-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5-[(trans-4-methylsulfanyl-tetrahydro-furan-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2- On 5.375.37 426.3426.3 5-{4-[트랜스-2-(피리미딘-2-일설파닐)-사이클로펜틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [trans-2- (pyrimidin-2-ylsulfanyl) -cyclopentylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 6.326.32 488.3488.3 5-[4-(인단-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (Indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.866.86 426.3426.3 5-{4-[2-(2-하이드록시-에틸설파닐)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (2-hydroxy-ethylsulfanyl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On 4.664.66 414.3414.3 5-{4-[2-(피리딘-3-일옥시)-프로필아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (pyridin-3-yloxy) -propylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.205.20 445.3445.3 5-{4-[2-(6-메틸-피리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (6-Methyl-pyridin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 5.005.00 429.3429.3 5-{4-[(2,3-디하이드로-벤조[1,4]디옥신-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(2,3-dihydro-benzo [1,4] dioxin-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one 5.015.01 458.2458.2 5-{4-[(1-메틸-1H-피라졸-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-Methyl-1H-pyrazol-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 4.604.60 404.3404.3 5-{4-[(4,5,6,7-테트라하이드로-벤조티아졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4,5,6,7-tetrahydro-benzothiazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indol-2-one 5.935.93 461.2461.2 5-[4-(1-페닐-3-[1,2,4]트리아졸-1-일-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1-phenyl-3- [1,2,4] triazol-1-yl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3- Dihydro-indol-2-one 5.245.24 495.2495.2 5-(4-이소부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-isobutylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.126.12 366.4366.4 5-[4-(2-사이클로헥실-1-하이드록시메틸-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-cyclohexyl-1-hydroxymethyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.416.41 450.4450.4 2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로피온산 메틸 에스테르2- [2- (2-Oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propionic acid methyl ester 5.265.26 396.3396.3 5-(4-사이클로헥실아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-cyclohexylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.826.82 392.3392.3 5-[4-(3-하이드록시-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-hydroxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.244.24 368.3368.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[2-(4-메틸-1H-이미다졸-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (4-Methyl-1H-imidazol-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indole-2-one 3.543.54 418.3418.3 5-[4-(테트라하이드로-푸란-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (tetrahydro-furan-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.894.89 380.3380.3 5-[4-(디사이클로프로필메틸-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (Dicyclopropylmethyl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.596.59 404.3404.3 5-{4-[2-(5-메틸-4H-[1,2,4]트리아졸-3-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (5-methyl-4H- [1,2,4] triazol-3-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino}- 1,3-dihydro-indol-2-one 4.004.00 419.3419.3 5-[4-(2-에틸설파닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- [4- (2-ethylsulfanyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.995.99 398.3398.3 5-[4-(2-페녹시-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-phenoxy-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.576.57 444.2444.2 5-{4-[(1-에틸-5-옥소-피롤리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-ethyl-5-oxo-pyrrolidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro Indole-2-one 4.574.57 435.2435.2 5-(4-{[1-(2-메톡시-에틸)-5-옥소-피롤리딘-3-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-{[1- (2-methoxy-ethyl) -5-oxo-pyrrolidin-3-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 4.444.44 465.2465.2 5-[4-(벤즈하이드릴-아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (benzhydryl-amino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 7.267.26 476.2476.2 5-{4-[2-(1-메틸1H-피라졸-4-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1-methyl1H-pyrazol-4-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 4.904.90 418.3418.3 5-{4-[(4-메틸-1H-이미다졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-Methyl-1H-imidazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 3.403.40 404.2404.2 5-{4-[(5-사이클로프로필-1H-피라졸-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(5-cyclopropyl-1H-pyrazol-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.005.00 430.2430.2 5-{4-[2-(4-메틸-티아졸-5-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (4-Methyl-thiazol-5-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 5.185.18 435.2435.2 5-{4-[2-(1H-벤조이미다졸-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (1H-Benzoimidazol-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 4.394.39 454.2454.2 5-{4-[(5-메틸-[1,3,4]옥사디아졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(5-methyl- [1,3,4] oxadiazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indol-2-one 4.254.25 406.3406.3 5-{4-[(5-페닐-4H-[1,2,4]트리아졸-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(5-phenyl-4H- [1,2,4] triazol-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one 4.924.92 467.3467.3 5-{4-[(1H-인돌-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1H-Indol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 6.106.10 439.3439.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) MS 데이타 (M+H)MS data (M + H) 5-{4-[(1,5-디메틸-1H-피라졸-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1,5-Dimethyl-1H-pyrazol-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro- Indole-2-one 4.774.77 418.3418.3 5-{4-[(벤조티아졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(benzothiazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.775.77 457.2457.2 5-{4-[(3-메틸-이속사졸-5-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(3-methyl-isoxazol-5-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On 5.025.02 405.3405.3 5-{4-[(4-메틸-티아졸-2-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(4-methyl-thiazol-2-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On 5.125.12 421.2421.2 5-{4-[1-(4-메틸-티아졸-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [1- (4-Methyl-thiazol-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 5.625.62 435.2435.2 5-{5-트리플루오로메틸-4-[(1,3,5-트리메틸-1H-피라졸-4-일메틸)-아미노]-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {5-trifluoromethyl-4-[(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl) -amino] -pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 4.954.95 432.2432.2 5-{4-[1-(2-메틸-티아졸-4-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [1- (2-Methyl-thiazol-4-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 5.695.69 435.3435.3 5-{4-[(3-메틸-이미다조[2,1-b]티아졸-6-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(3-methyl-imidazo [2,1-b] thiazol-6-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one 5.035.03 460.3460.3 5-{4-[1-(5-메틸-4H-[1,2,4]트리아졸-3-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [1- (5-Methyl-4H- [1,2,4] triazol-3-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino}- 1,3-dihydro-indol-2-one 4.204.20 419.3419.3 5-{4-[1-(3,5-디메틸-1H-피라졸-4-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [1- (3,5-Dimethyl-1H-pyrazol-4-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 5.025.02 432.3432.3 5-{4-[2-(3,5-디메틸-1H-피라졸-4-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (3,5-Dimethyl-1H-pyrazol-4-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 4.854.85 432.4432.4 5-{4-[2-(4,6-디메틸-피리미딘-2-일)-에틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (4,6-Dimethyl-pyrimidin-2-yl) -ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.175.17 444.4444.4 5-{4-[2-(4-메틸-5,6,7,8-테트라하이드로-퀴나졸린-2-일)-에틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2- (4-Methyl-5,6,7,8-tetrahydro-quinazolin-2-yl) -ethylamino-5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.885.88 484.4484.4 5-[4-(2-티아졸-4-일-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- [4- (2-thiazol-4-yl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.185.18 421.3421.3 5-(4-디메틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-dimethylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 5.605.60 338.3338.3 5-{4-[(1-피리미딘-2-일-피페리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-pyrimidin-2-yl-piperidin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 6.176.17 485.4485.4 5-[4-(인단-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (Indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 6.856.85 426.3426.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) LRMS (MH+)LRMS (MH +) N-메틸-N-{3-[({메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노})-메틸]-페닐}-메탄설폰아미드N-methyl-N- {3-[({methyl- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Yl] -amino})-methyl] -phenyl} -methanesulfonamide 6.086.08 521.3521.3 N-메틸-N-{4-메틸-3-[({메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노})-메틸]-페닐}-메탄설폰아미드N-methyl-N- {4-methyl-3-[({methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl- Pyrimidin-4-yl] -amino})-methyl] -phenyl} -methanesulfonamide 6.246.24 535.8535.8 N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 6.236.23 507.2507.2 N-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 6.286.28 507.2507.2 N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 6.126.12 507.3507.3 N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (2-Methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 5.715.71 507.3507.3 5-[4-(3-메탄설포닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (3-methanesulfonyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 4.424.42 430.4430.4 N-메틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-methyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide 5.955.95 521.2521.2 N-(3-메탄설포닐아미노-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N- (3-methanesulfonylamino-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -methanesulfonamide 4.854.85 586.2586.2 N-메틸-N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-methyl-N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide 5.875.87 521.3521.3 N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide 5.865.86 521.3521.3 N-메틸-N-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-Methyl-N- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide 5.975.97 521.3521.3 5-{4-[((1S,2R)-2-하이드록시-사이클로헥실메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[((1S, 2R) -2-hydroxy-cyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-on 5.565.56 422.3422.3 5-[4-((1R,2S)-2-하이드록시-인단-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4-((1R, 2S) -2-hydroxy-indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole- 2-on 5.665.66 442.4442.4 5-[4-((S)-1-하이드록시메틸-2-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4-((S) -1-hydroxymethyl-2-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2 -On 5.545.54 444.3444.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) LRMS (MH+)LRMS (MH +) N-(3-(메탄설포닐-메틸-아미노)-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드N- (3- (methanesulfonyl-methyl-amino) -5-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl- Pyrimidin-4-ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide 5.365.36 614.2614.2 5-{4-[(1-하이드록시-사이클로펜틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 5.25.2 408.2408.2 N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페리딘-2-일)-메탄설폰아미드N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -ferridin-2-yl) -methanesulfonamide 5.265.26 508.2508.2 N-(3-플루오로-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드N- (3-fluoro-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide 5.865.86 525.2525.2 5-{4-[2-((S)-1-메탄설포닐-피롤리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2-((S) -1-Methanesulfonyl-pyrrolidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one 5.325.32 485.4485.4 5-{4-[(1-하이드록시-사이클로부틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(1-hydroxy-cyclobutylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one 4.914.91 394.3394.3 5-{4-[(2-((R)-1-메탄설포닐-피롤리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(2-((R) -1-Methanesulfonyl-pyrrolidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1 , 3-dihydro-indol-2-one 5.325.32 485.4485.4 N-(2-플루오로-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드N- (2-Fluoro-6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide 5.925.92 525.2525.2 N-(4-플루오로-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드N- (4-fluoro-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide 5.785.78 525.3525.3 N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide 5.175.17 508.1508.1 N-{2,2-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-N-메틸-메탄설폰아미드N- {2,2-dimethyl-3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -N-methyl-methanesulfonamide 5.75.7 487.3487.3 N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide 5.615.61 508.2508.2 N-(2,4-디플루오로-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드N- (2,4-difluoro-6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide 5.985.98 543.2543.2 5-[4-((R)-1-메탄설포닐-피페리딘-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4-((R) -1-methanesulfonyl-piperidin-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole 2-on 5.245.24 471.3471.3 N-메틸-N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드N-Methyl-N- (6-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide 5.585.58 522.2522.2

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) LRMS (MH+)LRMS (MH +) N-메틸-N-(5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드N-methyl-N- (5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide 4.794.79 508.2508.2 5-[4-(1-메탄설포닐-피페리딘-4-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (1-Methanesulfonyl-piperidin-4-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.265.26 471.2471.2 5-{4-[메틸-((R)-1-페닐-에틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [Methyl-((R) -1-phenyl-ethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On 7.237.23 428.3428.3 5-(4-벤질아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-benzylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.056.05 400.3400.3 N-(4,6-디메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-N-메틸-메탄설폰아미드N- (4,6-dimethyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amino] -methyl} -pyridin-2-yl) -N-methyl-methanesulfonamide 6.16.1 536.3536.3 5-(4-tert-부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-tert-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one 6.496.49 366.2366.2 5-[4-((1R,5S,6S)-3-메탄설포닐-3-아자-비사이클로[3.1.0]헥스-6-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4-((1R, 5S, 6S) -3-methanesulfonyl-3-aza-bicyclo [3.1.0] hex-6-ylamino) -5-trifluoromethyl-pyrimidine-2 -Ylamino] -1,3-dihydro-indol-2-one 4.994.99 469.3469.3 N-메틸-N-{3-메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-부틸}-메탄설폰아미드N-Methyl-N- {3-methyl-3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -butyl} -methanesulfonamide 5.75.7 487.2487.2 N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드N- (6-Methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide 5.275.27 508.2508.2 5-{4-[(2-메탄설포닐-피리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(2-methanesulfonyl-pyridin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On 4.794.79 479479 2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 아미드2- [2- (2-Oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid amide 4.194.19 417.1417.1 N-(3-메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노}-프로필)-메탄설폰아미드N- (3-Methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -amino}- Propyl) -methanesulfonamide 5.075.07 459.3459.3 N-(2-{메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노}-에틸)-메탄설폰아미드N- (2- {methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -amino} -Ethyl) -methanesulfonamide 4.894.89 445.3445.3 5-[4-(2-메탄설포닐메틸-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온5- [4- (2-methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one 5.385.38 492.3492.3 2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 디메틸아미드2- [2- (2-Oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid dimethylamide 5.095.09 445.2445.2 N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrazin-2-yl) -methanesulfonamide 5.495.49 509.2509.2 에탄설폰산 메틸-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Methyl ethanesulfonic acid- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -phenyl) -amide 5.965.96 521.3521.3

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) LRMS (MH+)LRMS (MH +) 에탄설폰산 (2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Ethanesulfonic acid (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -Phenyl) -amide 6.236.23 507.2507.2 N-에틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드N-ethyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide 5.545.54 522.2522.2 N-{1,1-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드N- {1,1-dimethyl-3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide 5.185.18 473.1473.1 N-(5,6-디메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-N-메틸-메탄설폰아미드N- (5,6-dimethyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amino] -methyl} -pyrazin-2-yl) -N-methyl-methanesulfonamide 6.316.31 537.1537.1 5-{4-[((R)-4-메탄설포닐-모르폴린-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[((R) -4-methanesulfonyl-morpholin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indole-2-one 4.624.62 487.2487.2 프로판-1-설폰산 (2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Propane-1-sulfonic acid (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -amide 6.66.6 521.2521.2 5-{4-[2-((R)-4-메탄설포닐-모르폴린-3-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4- [2-((R) -4-methanesulfonyl-morpholin-3-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indol-2-one 4.994.99 501.1501.1 에탄설폰산 메틸-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-아미드Methyl ethanesulfonic acid- (3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -pyridin-2-yl) -amide 5.645.64 522.2522.2 트리플루오로-N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드Trifluoro-N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -propyl} -methanesulfonamide 6.426.42 513.3513.3 사이클로프로판설폰산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Cyclopropanesulfonic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -amide 5.55.5 485.3485.3 N-에틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-ethyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide 5.945.94 521.2521.2 에탄설폰산 메틸-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Methane-ethanesulfonic acid- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide 에탄설폰산 에틸-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Ethanesulfonic acid ethyl- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -phenyl) -amide 6.226.22 535535 에탄설폰산 에틸-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Ethanesulfonic acid ethyl- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide 6.556.55 549549 N-에틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-ethyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide 6.276.27 535.1535.1 에탄설폰산 (5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Ethanesulfonic acid (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -amide 6.596.59 521.1521.1

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) LRMS (MH+)LRMS (MH +) 에탄설폰산 (3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Ethanesulfonic acid (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -amide 6.76.7 521.3521.3 에탄설폰산 메틸-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드Methyl ethanesulfonic acid- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide 6.336.33 535.2535.2 2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 메틸아미드2- [2- (2-Oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid methylamide 4.64.6 431.1431.1 에탄설폰산 {3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드Ethanesulfonic acid {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl}- amides 4.874.87 459.1459.1 C-메탄설포닐-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드C-methanesulfonyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide 4.844.84 523523 에탄설폰산 {2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드Ethanesulfonic acid {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl}- amides 4.654.65 445.2445.2 C-메탄설포닐-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드C-methanesulfonyl-N- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -methanesulfonamide 4.624.62 509509 N-메틸-N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드N-methyl-N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide 5.635.63 522.1522.1 5-(4-{[1-(2,2,2-트리플루오로-아세틸)-피페리딘-3-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온5- (4-{[1- (2,2,2-Trifluoro-acetyl) -piperidin-3-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino ) -1,3-dihydro-indol-2-one 6.046.04 503.1503.1 2,2,2-트리플루오로-에탄설폰산 {3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드2,2,2-trifluoro-ethanesulfonic acid {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine -4-ylamino] -propyl} -amide 5.565.56 513.2513.2 N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-2-일)-메탄설폰아미드N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-2-yl) -methanesulfonamide 5.215.21 509.3509.3 N-사이클로프로필-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드N-cyclopropyl-N- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide 6.016.01 533.3533.3 N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) -methanesulfonamide 4.954.95 509.2509.2 N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrazin-2-yl) -methanesulfonamide 5.35.3 509.4509.4 N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide 5.545.54 508.3508.3 N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노))-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-4-일)-메탄설폰아미드N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino))-5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -pyridin-4-yl) -methanesulfonamide 5.555.55 508.4508.4

화합물 명칭Compound name HPLC 체류시간 (분)HPLC retention time (minutes) LRMS (MH+)LRMS (MH +) N-사이클로프로필-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드N-cyclopropyl-N- (3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -pyridin-2-yl) -methanesulfonamide 5.65.6 534.1534.1 N-메틸-N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드N-Methyl-N- (6-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide 5.935.93 523.4523.4 5-{4-[(2-메탄설포닐메틸-피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온5- {4-[(2-Methanesulfonylmethyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-on 5.45.4 493.2493.2 N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide 4.774.77 508.2508.2

본 발명은 본 명세서에 기술된 특정의 구체예에 의해서 범주가 제한되지 않는다. 실제로, 본 명세서에 기술된 것 이외에도 본 발명의 다양한 변형예는 전술한 설명 및 첨부된 도면으로부터 본 기술분야에서 숙련된 전문가에게 자명할 것이다. 이러한 구체예도 첨부된 특허청구범위에 속하는 것이다.The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will be apparent to those skilled in the art from the foregoing description and the accompanying drawings. Such embodiments are also within the scope of the appended claims.

본 명세서에서 인용된 모든 특허, 특허공보, 시험방법 및 그 밖의 다른 물질은 온전히 본 명세서에 참고로 포함된다.All patents, patent publications, test methods, and other materials cited herein are hereby incorporated by reference in their entirety.

Claims (12)

하기 화학식 1의 화합물, 또는 그의 약제학적으로 허용되는 염, 용매화물, 수화물 또는 프로드럭.A compound of Formula 1, or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof. [화학식 1][Formula 1]
Figure 112006082893189-PCT00025
Figure 112006082893189-PCT00025
 상기 식에서,Where n은 1 내지 3의 정수이며;n is an integer from 1 to 3; 각각의 R1은 수소, 하이드록시, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -NR5R6, -SR7, -SOR7, -SO2R7, -CO2R12, -CONR5R6, -SO2NR5R6, -NHCOR12, -NR12CONR5R6, 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택되는 치환체이고, 여기에서 상기 R1 치환체인 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -NR5R6, -SR7, -SOR7, -SO2R7, -CO2R12, -CONR5R6, -SO2NR5R6, -NHCOR12, -NR12CONR5R6, 및 -NR12SO2R7은 수소, 할로겐, 하이드록시, -CF3, -CN, -(C1-C6)알킬, -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며;Each R 1 is hydrogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -O (C 1 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -NR 5 R 6 , -SR 7 , -SOR 7 , -SO 2 R 7 ,- A substituent independently selected from the group consisting of CO 2 R 12 , -CONR 5 R 6 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 , and -NR 12 SO 2 R 7 , Wherein the R 1 substituent is-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -O (C 1 -C 6 ) alkyl , -O (C 3 -C 7 ) cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -NR 5 R 6 , -SR 7 , -SOR 7 , -SO 2 R 7 , -CO 2 R 12 , -CONR 5 R 6 , -SO 2 NR 5 R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 , and -NR 12 SO 2 R 7 are hydrogen, halogen, hydroxy, -CF 3 , -CN ,-(C 1 -C 6 ) alkyl, -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , Consisting of -CONR 5 R 6 and -CONR 5 R 8 Optionally substituted by one to three residues independently selected from the group; 각각의 R2는 수소, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12 및 -CONR5R6로 구성된 군으로부터 독립적으로 선택되는 치환체이고, 여기에서 상기 R2 치환체인 -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12 및 -CONR5R6은 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선 택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 R2 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있거나;Each R 2 is hydrogen,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 and -CONR 5 R 6 is a substituent independently selected from the group consisting of the R 2 substituents-(C 1 -C 6 ) alkyl ,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 and -CONR 5 R 6 are hydrogen, halogen, hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl ,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -CONR 5 R 6 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 5 Optionally substituted by 1 to 3 residues independently selected from the group consisting of R 6 , -NHCOR 12 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 , wherein said-(C 2 -C 6) Unknown Carbonyl, and - (C 2 -C 6) alkynyl R 2 moieties may be optionally substituted by one to three groups R 12; R1 및 R2는 이들이 부착된 원자(들)과 함께 사이클릭 기, -(C3-C10)사이클로알킬 또는 -(C2-C9)헤테로사이클릴을 형성할 수 있고, 여기에서 상기 사이클릭 기는 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR5R6, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR5R6, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR5R6, -NHCOR12, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 상기 사이클릭 기의 상기 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R12 기에 의해서 임의로 치환될 수 있고, 상기의 사이클릭 기는 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재되며;R 1 and R 2 together with the atom (s) to which they are attached may form a cyclic group, — (C 3 -C 10 ) cycloalkyl or — (C 2 -C 9 ) heterocyclyl, wherein Cyclic groups are hydrogen, halogen, hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) Alkynyl, -C = N-OH, -C = NO ((C 1 -C 6 ) alkyl), -NR 5 R 6 , -OR 12 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9) heterocyclyl, -CO 2 R 12, -CONR 5 R 6, -CONR 5 R 8, -SR 7, -SOR 7, -SO 2 R 7, -SO 2 NR 5 R 6, -NHCOR 12 , -NR 12 CONR 5 R 6 and -NR 12 SO 2 R 7 is optionally substituted with 1 to 3 residues independently selected from the above-(C 2 -C 6 of the cyclic group ) Alkenyl and-(C 2 -C 6 ) alkynyl moieties may be optionally substituted by one to three R 12 groups, wherein the cyclic groups are-(C═O), —SO 2 , —S—, A line from the group consisting of -O-, -N-, -NH-, and -NR 12 Optionally one to three selected elements are interposed; R3는 (a) 수소; R 3 is (a) hydrogen; (b) 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C6-C10)아릴 또는 -(C1-C9)헤테로아릴 (여기에서, 상기의 -(C6-C10)아릴 또는 -(C1-C9)헤테로아릴은 -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다); (b) halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl) 2 ,-(C 3- C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 1- C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ( (C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl,- O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3 -C 10 ) cycloalkyl,-( CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl,- (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) alkyl, -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3 , -SO 2 NH 2 , -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1 -C 6 ) alkyl) ((C 3 -C 6 ) cyclo -(C 6 -C optionally substituted by 1 to 3 residues independently selected from the group consisting of alkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 10 ) aryl or-(C 1 -C 9 ) heteroaryl (wherein-(C 6 -C 10 ) aryl or-(C 1 -C 9 ) heteroaryl is -S-, -O-,- Optionally interrupted by 1 to 3 elements selected from the group consisting of N—, —NH— and —NR 12 ); (c) 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1-C6)알킬-(C2-C9)헤테로사이클릴 (여기에서, 상기의 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1- C6)알킬-(C2-C9)헤테로사이클릴은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다); 및 (c) halogen, hydroxy, - (C 1 -C 6) alkyl, - (C 1 -C 6) alkyl, -P (O) (O (C 1 -C 6) alkyl) 2, - (C 3 - C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 1- C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ( (C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl,- O-SO 2 (C 1 -C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-( CO) (C 3 -C 10 ) cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl, - (CO) O (C 1 -C 6) alkyl, - (CO) O (C 3 -C 10) cycloalkyl, - (CO) O (C 6 -C 10) aryl, - (CO ) O (C 2 -C 9 ) heterocyclyl,-(CO) O (C 1 -C 9 ) heteroaryl,-(CO) (C 1 -C 6 ) alkyl -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3, -SO 2 NH 2, -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1- C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 are independently selected from the group consisting of -(C 3 -C 10 ) cycloalkyl, optionally substituted by three residues,-(C 2 -C 9 ) heterocyclyl and-(C 1 -C 6 ) alkyl- (C 2 -C 9 ) heterocycle Reel (wherein-(C 3 -C 10 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl and-(C 1 -C 6 ) alkyl- (C 2 -C 9 ) heterocyclyl Is optionally interrupted by 1 to 3 elements selected from the group consisting of — (C═O), —SO 2 , —S—, —O—, —N—, —NH—, and —NR 12 ); And (d) 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬 (여기에서, 상기의 -(C1-C6)알킬은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)로 구성된 군으로부터 선택된 치환체이고,(d) halogen, hydroxy, - (C 1 -C 6) alkyl, - (C 1 -C 6) alkyl, -P (O) (O (C 1 -C 6) alkyl) 2, - (C 3 - C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ((C 1- C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) alkyl), -N ( (C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl,- O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3 -C 10 ) cycloalkyl,-( CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl,- (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) alkyl, -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3 , -SO 2 NH 2 , -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1 -C 6 ) alkyl) ((C 3 -C 6 ) cyclo -(C 1 -C 6 ) optionally substituted by 1 to 3 residues selected from the group consisting of alkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 Alkyl, wherein — (C 1 -C 6 ) alkyl is a group consisting of — (C═O), —SO 2 , —S—, —O—, —N—, —NH—, and —NR 12 1 to 3 elements selected from are optionally interposed), a substituent selected from the group consisting of 여기에서, 각각의 R3 (b)-(d) 치환체, 잔기 또는 원소는 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴, -(C1-C9)헤테로아릴, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -C=N-OH, -C=N-O(C1-C6 알킬), -NR5R6, -SR7, -SOR7, -SO2R7, -CO2R12, -CONR5R6, -SO2NR5R6, -NHCOR5, -NR12CONR5R6 및 -NR12SO2R7로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 래디칼에 의해서 임의로 치환되며;Wherein each R 3 (b)-(d) substituent, residue or element is hydrogen, halogen, hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-( C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) Aryl,-(C 1 -C 9 ) heteroaryl, -O (C 1 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -C = N-OH, -C = NO (C 1 -C 6 alkyl), -NR 5 R 6 , -SR 7 , -SOR 7 , -SO 2 R 7 , -CO 2 R 12 , -CONR 5 R 6 , —SO 2 NR 5 R 6 , —NHCOR 5 , —NR 12 CONR 5 R 6 and —NR 12 SO 2 R 7 optionally substituted with 1 to 3 radicals independently selected from the group consisting of; R4는 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴로 구성된 군으로부터 선택된 치환체이고, 여기에서 상기의 -(C1-C6)알킬, -(C3-C7)사이클로알킬 및 -(C2-C9)헤테로사이클릴 R4 치환체는 수소, 할로겐, 하이드록시, -(C1-C6)알킬, -CN, -NR5R6, -OR5, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -SO2NR5R6, -NR12SO2R7, -SO2R7 및 -CONR5R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 상기 -CONR5R8 기의 R5 및 R8은 이들이 부착된 원자와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있고;R 4 is a substituent selected from the group consisting of hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl, wherein C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl and-(C 2 -C 9 ) heterocyclyl R 4 substituents are hydrogen, halogen, hydroxy,-(C 1 -C 6 ) alkyl , -CN, -NR 5 R 6 , -OR 5 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 12 , -SO 2 NR 5 R 6 , -NR 12 SO 2 R 7 , -SO 2 R 7 and -CONR 5 R 8 are optionally substituted with 1 to 3 residues independently selected from the group consisting of R 5 of the above-CONR 5 R 8 groups And R 8 together with the atoms to which they are attached may form — (C 2 -C 9 ) heterocyclyl; R5 및 R6는 각각 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴, -(C1-C9)헤테로아릴, -COR12 및 -SO2R12로 구성된 군으로부터 독립적으로 선택된 치환체이며, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴, -(C1-C9)헤테로아릴, -COR12 및 -SO2R12인 R5 또는 R6 치환체는 수소, 할로겐, -CF3, -CN, -(C1-C6)알킬, -NH(C1-C6)알킬, -NH(C3-C7)사이클로알킬, -NH(C2-C9)헤테로사이클릴, -NH(C6-C10)아릴, -NH(C1-C9)헤테로아릴, -N((C1-C6)알킬)2, -N((C3-C7)사이클로알킬)2, -N((C2-C9)헤테로사이클릴)2, -N((C6-C10)아릴)2, -N((C1-C9)헤테로아릴)2, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -O(C6-C10)아릴, -O(C1-C9)헤테로아릴, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R7, -SO2NR5R6, -NR12SO2R7, -SO2R7, -CONH2, -CONHR7 및 -CONR7R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되고, 여기에서 상기 -CONR7R8의 R7 및 R8은 이들이 부착된 질소와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있거나;R 5 and R 6 are each hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) Aryl,-(C 1 -C 9 ) heteroaryl, -COR 12 and -SO 2 R 12 is a substituent independently selected from the group consisting of-(C 1 -C 6 ) alkyl,-(C 3- C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl,-(C 1 -C 9 ) heteroaryl, -COR 12 and -SO 2 R 12 5 or R 6 substituents are hydrogen, halogen, -CF 3 , -CN,-(C 1 -C 6 ) alkyl, -NH (C 1 -C 6 ) alkyl, -NH (C 3 -C 7 ) cycloalkyl, -NH (C 2 -C 9 ) heterocyclyl, -NH (C 6 -C 10 ) aryl, -NH (C 1 -C 9 ) heteroaryl, -N ((C 1 -C 6 ) alkyl) 2 , -N ((C 3 -C 7 ) cycloalkyl) 2 , -N ((C 2 -C 9 ) heterocyclyl) 2 , -N ((C 6 -C 10 ) aryl) 2 , -N ((C 1 -C 9 ) heteroaryl) 2 , -O (C 1 -C 6 ) alkyl, -O (C 3 -C 7 ) cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -O (C 6 -C 10) aryl, -O (C 1 -C 9) heteroaryl, - (C 3 -C 7) used Claw-alkyl, - (C 2 -C 9) heterocyclyl, -CO 2 R 7, -SO 2 NR 5 R 6, -NR 12 SO 2 R 7, -SO 2 R 7, -CONH 2, -CONHR 7 And-1 to 3 residues independently selected from the group consisting of -CONR 7 R 8 , wherein R 7 and R 8 of -CONR 7 R 8 together with the nitrogen to which they are attached-(C 2- C 9 ) may form heterocyclyl; R5 및 R6가 이들이 부착된 원자(들)와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있으며, 여기에서 상기 -(C2-C9)헤테로사이클릴 기는 수소, 할로겐, 하이드록시, -CF3, -NO2, -CN, -(C1-C6)알킬, -(C2-C6)알케닐, -(C2-C6)알키닐, -C=N-OH, -C=N-O((C1-C6)알킬), -NR7R8, -OR12, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R12, -CONR7R8, -CONR5R8, -SR7, -SOR7, -SO2R7, -SO2NR7R8, -NHCOR12, -NR12CONR7R8 및 -NR12SO2R7로 구성된 군으로부터 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되고, 여기에서 상기 -(C2-C9)헤테로사이클릴 기의 -(C2-C6)알케닐 및 -(C2-C6)알키닐 잔기는 1 내지 3개의 R7 기에 의해서 임의로 치환되고, 상기의 -(C2-C9)헤테로사이클릴 기는 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재되며;R 5 and R 6 together with the atom (s) to which they are attached may form-(C 2 -C 9 ) heterocyclyl, wherein the-(C 2 -C 9 ) heterocyclyl group is hydrogen, halogen , Hydroxy, -CF 3 , -NO 2 , -CN,-(C 1 -C 6 ) alkyl,-(C 2 -C 6 ) alkenyl,-(C 2 -C 6 ) alkynyl, -C = N-OH, -C = NO ( (C 1 -C 6) alkyl), -NR 7 R 8, -OR 12, - (C 3 -C 7) cycloalkyl, - (C 2 -C 9) heterocyclyl Reel, -CO 2 R 12 , -CONR 7 R 8 , -CONR 5 R 8 , -SR 7 , -SOR 7 , -SO 2 R 7 , -SO 2 NR 7 R 8 , -NHCOR 12 , -NR 12 CONR 7 R 8, and -NR 12 SO 2 R 7 is optionally substituted by one to three moieties selected from the group consisting of, where the - (C 2 -C 9) heterocyclyl group of - (C 2 -C 6 ) Alkenyl and-(C 2 -C 6 ) alkynyl residues are optionally substituted by one to three R 7 groups, wherein the-(C 2 -C 9 ) heterocyclyl group is-(C═O),- 1 to 3 selected from the group consisting of SO 2 , -S-, -O-, -N-, -NH- and -NR 12 An element is optionally interposed; R7은 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10) 아릴 및 -(C1-C9)헤테로아릴로 구성된 군으로부터 선택된 치환체이고, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 R7 치환체는 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NR12 2 및 -O(C1-C6)알킬로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며;R 7 is — (C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl is a substituent selected from the group consisting of wherein-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl R 7 substituents are hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NR 12 2 and- Optionally substituted by 1 to 3 residues independently selected from the group consisting of O (C 1 -C 6 ) alkyl; R8은 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴로 구성된 군으로부터 선택된 치환체이고, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 R8 치환체는 수소, 할로겐, 하이드록시, -CN, -(C1-C6)알킬, -NH2, -NHR9, -NR9 2, -OR9, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R10, -CONH2, -CONHR10 및 -CONR10R11로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 -CONR10R11의 R10 및 R11은 이들이 부착된 질소 원자와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있고;R 8 is hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl and-( C 1 -C 9 ) heteroaryl and a substituent selected from the group consisting of wherein-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocycle Aryl,-(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl R 8 substituents are hydrogen, halogen, hydroxy, -CN,-(C 1 -C 6 ) alkyl, -NH 2 , -NHR 9 , -NR 9 2 , -OR 9 ,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl, -CO 2 R 10 , -CONH 2 , -CONHR 10 and -CONR 10 R 11 and optionally by one to three moieties independently selected from the group consisting of substitution, where in R 10 and R 11 of -CONR 10 R 11 together with the nitrogen atom to which they are attached a - (C 2 -C 9 ) can form heterocyclyl; R9 및 R10은 각각 -(C1-C6)알킬이며;R 9 and R 10 are each-(C 1 -C 6 ) alkyl; R11은 수소 또는 -(C1-C6)알킬이고;R 11 is hydrogen or-(C 1 -C 6 ) alkyl; R12는 수소, -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴로 구성된 군으로부터 선택된 치환체이며, 여기에서 상기 -(C1-C6)알킬, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 R12 치환체는 수소, 할로겐, -CF3, -CN, -(C1-C6)알킬, -NH(C1-C6)알킬, -NH(C3-C7)사이클로알킬, -NH(C2-C9)헤테로사이클릴, -NH(C6-C10)아릴, -NH(C1-C9)헤테로아릴, -N((C1-C6)알킬)2, -N((C3-C7)사이클로알킬)2, -N((C2-C9)헤테로사이클릴)2, -N((C6-C10)아릴)2, -N((C1-C9)헤테로아릴)2, -O(C1-C6)알킬, -O(C3-C7)사이클로알킬, -O(C2-C9)헤테로사이클릴, -O(C6-C10)아릴, -O(C1-C9)헤테로아릴, -(C3-C7)사이클로알킬, -(C2-C9)헤테로사이클릴, -CO2R7, -CONH2, -CONHR7 및 -CONR7R8로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환되며, 여기에서 -CONR7R8의 R7 및 R8은 이들이 부착된 질소 원자와 함께 -(C2-C9)헤테로사이클릴을 형성할 수 있다.R 12 is hydrogen,-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl,-(C 6 -C 10 ) aryl and-( C 1 -C 9 ) heteroaryl, wherein the substituent is selected from the group consisting of-(C 1 -C 6 ) alkyl,-(C 3 -C 7 ) cycloalkyl,-(C 2 -C 9 ) heterocycle The aryl,-(C 6 -C 10 ) aryl and-(C 1 -C 9 ) heteroaryl R 12 substituents are hydrogen, halogen, -CF 3 , -CN,-(C 1 -C 6 ) alkyl, -NH ( C 1 -C 6 ) alkyl, -NH (C 3 -C 7 ) cycloalkyl, -NH (C 2 -C 9 ) heterocyclyl, -NH (C 6 -C 10 ) aryl, -NH (C 1- C 9 ) heteroaryl, -N ((C 1 -C 6 ) alkyl) 2 , -N ((C 3 -C 7 ) cycloalkyl) 2 , -N ((C 2 -C 9 ) heterocyclyl) 2 , -N ((C 6 -C 10 ) aryl) 2 , -N ((C 1 -C 9 ) heteroaryl) 2 , -O (C 1 -C 6 ) alkyl, -O (C 3 -C 7 ) Cycloalkyl, -O (C 2 -C 9 ) heterocyclyl, -O (C 6 -C 10 ) aryl, -O (C 1 -C 9 ) heteroaryl,-(C 3 -C 7 ) cycloalkyl, -(C 2 -C 9 ) heterocyclyl, -CO 2 R 7 , -CONH 2 , -CONHR 7 and- Optionally substituted by one to three residues independently selected from the group consisting of CONR 7 R 8 , wherein R 7 and R 8 of -CONR 7 R 8 together with the nitrogen atom to which they are attached-(C 2 -C 9 Heterocyclyl can be formed. 제 1 항에 있어서, R3가 수소인 화합물.The compound of claim 1, wherein R 3 is hydrogen. 제 1 항에 있어서, R3가 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6 로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C6-C10)아릴 및 -(C1-C9)헤테로아릴 (여기에서, 상기의 -(C6-C10)아릴 또는 -(C1-C9)헤테로아릴은 -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)로 구성된 군으로부터 선택되는 화합물.The compound of claim 1, wherein R 3 is halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl) 2 ,-(C 3 -C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl) , -N ((C 1 -C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) Alkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1- C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3 -C 10 ) Cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl, - (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) Al -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3, -SO 2 NH 2, -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1- C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO 2 NR 5 R 6 are independently selected from the group consisting of the by 3 residues, optionally substituted - (C 6 -C 10) aryl, and - (C 1 -C 9) heteroaryl (wherein said - (C 6 -C 10) aryl or - (C 1 -C 9 ) heteroaryl is selected from the group consisting of one to three elements optionally selected from the group consisting of -S-, -O-, -N-, -NH- and -NR 12 ). 제 1 항에 있어서, R3가 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3- C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 독립적으로 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1-C6)알킬-(C2-C9)헤테로사이클릴 (여기에서, 상기의 -(C3-C10)사이클로알킬, -(C2-C9)헤테로사이클릴 및 -(C1-C6)알킬-(C2-C9)헤테로사이클릴은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)로 구성된 군으로부터 선택되는 화합물.The compound of claim 1, wherein R 3 is halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl) 2 ,-(C 3 -C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl) , -N ((C 1 -C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) Alkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1- C 6 ) alkyl, -O-SO 2 (C 1 -C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO ) CF 3 ,-(CO) (C 3 -C 10 ) cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl, - (CO) O (C 2 -C 9) heterocyclyl, - (CO) O (C 1 -C 9) heteroaryl Reel, - (CO) (C 1 -C 6) alkyl, -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 - C 6) cycloalkyl, -SO 2 CF 3 , -SO 2 NH 2 , -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) Alkyl) 2 , -SO 2 N ((C 1 -C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2 and -SO -(C 3 -C 10 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl and-(C 1- ), optionally substituted by 1 to 3 residues independently selected from the group consisting of 2 NR 5 R 6 C 6 ) alkyl- (C 2 -C 9 ) heterocyclyl, wherein-(C 3 -C 10 ) cycloalkyl,-(C 2 -C 9 ) heterocyclyl and-(C 1 -C 6 ) alkyl- (C 2 -C 9 ) heterocyclyl is selected from the group consisting of — (C═O), —SO 2 , —S—, —O—, —N—, —NH—, and —NR 12 ; 1 to 3 elements are optionally interrupted). 제 1 항에 있어서, R3가 할로겐, 하이드록시, -(C1-C6)알킬, -(C1-C6)알킬-P(O)(O(C1-C6)알킬)2, -(C3-C10)사이클로알킬, -(C6-C10)아릴, -(C2-C9)헤테로사이클릴, -(C1-C9)헤테로아릴, -NR5R6, -NHSO2(C1-C6)알킬, -NHSO2(C3-C6)사이클로알킬, -N((C1-C6)알킬)(SO2-C1-C6)알킬), -N((C1-C6)알킬)(SO2(C3-C6)사이클로알킬), -N((C3-C6)사이클로알킬)(SO2-C1-C6)알킬), -N((C3-C6)사이클로알킬)(SO2(C3-C6)사이클로알킬), -O(C1-C6)알킬, -O-SO2(C1-C6)알킬, -O-SO2(C3-C6)사이클로알킬, -(CO)(C1-C6)알킬, -(CO)CF3, -(CO)(C3-C10)사이클로알킬, -(CO)(C6-C10)아릴, -(CO)(C2-C9)헤테로사이클릴, -(CO)(C1-C9)헤테로아릴, -(CO)O(C1-C6)알킬, -(CO)O(C3-C10)사이클로알킬, -(CO)O(C6-C10)아릴, -(CO)O(C2-C9)헤테로사이클릴, -(CO)O(C1-C9)헤테로아릴, -(CO)(C1-C6)알킬-O(C1-C6)알킬, -SO2(C1-C6)알킬, -SO2(C3-C6)사이클로알킬, -SO2CF3, -SO2NH2, -SO2NH(C1-C6)알킬, -SO2NH(C3-C6)사이클로알킬, -SO2N((C1-C6)알킬)2, -SO2N((C1-C6)알킬)((C3-C6)사이클로알킬), -SO2N((C3-C6)사이클로알킬)2 및 -SO2NR5R6로 구성된 군으로부터 선택된 1 내지 3개의 잔기에 의해서 임의로 치환된 -(C1-C6)알킬 (여기에서, 상기의 -(C1-C6)알킬은 -(C=O), -SO2, -S-, -O-, -N-, -NH- 및 -NR12로 구성된 군으로부터 선택된 1 내지 3개의 원소가 임의로 개재된다)인 화합물.The compound of claim 1, wherein R 3 is halogen, hydroxy,-(C 1 -C 6 ) alkyl,-(C 1 -C 6 ) alkyl-P (O) (O (C 1 -C 6 ) alkyl) 2 ,-(C 3 -C 10 ) cycloalkyl,-(C 6 -C 10 ) aryl,-(C 2 -C 9 ) heterocyclyl,-(C 1 -C 9 ) heteroaryl, -NR 5 R 6 , -NHSO 2 (C 1 -C 6 ) alkyl, -NHSO 2 (C 3 -C 6 ) cycloalkyl, -N ((C 1 -C 6 ) alkyl) (SO 2 -C 1 -C 6 ) alkyl) , -N ((C 1 -C 6 ) alkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 -C 1 -C 6 ) Alkyl), -N ((C 3 -C 6 ) cycloalkyl) (SO 2 (C 3 -C 6 ) cycloalkyl), -O (C 1 -C 6 ) alkyl, -O-SO 2 (C 1- C 6 ) alkyl, -O-SO 2 (C 3 -C 6 ) cycloalkyl,-(CO) (C 1 -C 6 ) alkyl,-(CO) CF 3 ,-(CO) (C 3 -C 10 ) Cycloalkyl,-(CO) (C 6 -C 10 ) aryl,-(CO) (C 2 -C 9 ) heterocyclyl,-(CO) (C 1 -C 9 ) heteroaryl,-(CO) O (C 1 -C 6 ) alkyl,-(CO) O (C 3 -C 10 ) cycloalkyl,-(CO) O (C 6 -C 10 ) aryl,-(CO) O (C 2 -C 9 ) heterocyclyl, - (CO) O (C 1 -C 9) heteroaryl, - (CO) (C 1 -C 6) Al -O (C 1 -C 6) alkyl, -SO 2 (C 1 -C 6 ) alkyl, -SO 2 (C 3 -C 6 ) cycloalkyl, -SO 2 CF 3, -SO 2 NH 2, -SO 2 NH (C 1 -C 6 ) alkyl, -SO 2 NH (C 3 -C 6 ) cycloalkyl, -SO 2 N ((C 1 -C 6 ) alkyl) 2 , -SO 2 N ((C 1- 1 to 3 selected from the group consisting of C 6 ) alkyl) ((C 3 -C 6 ) cycloalkyl), -SO 2 N ((C 3 -C 6 ) cycloalkyl) 2, and -SO 2 NR 5 R 6 -(C 1 -C 6 ) alkyl optionally substituted by a moiety, wherein-(C 1 -C 6 ) alkyl is-(C═O), —SO 2 , —S—, —O—, Is optionally interrupted by 1 to 3 elements selected from the group consisting of -N-, -NH-, and -NR 12 ). 제 1 항 내지 5 항 중의 어느 한 항에 있어서, 하기 화학식 2로 표시되는 화합물.The compound according to any one of claims 1 to 5, represented by the following formula (2). [화학식 2][Formula 2]
Figure 112006082893189-PCT00026
Figure 112006082893189-PCT00026
 상기 식에서,Where A는 하기 화학식의 기로 구성된 군으로부터 선택되며,A is selected from the group consisting of groups of the formula
Figure 112006082893189-PCT00027
Figure 112006082893189-PCT00027
Figure 112006082893189-PCT00028
Figure 112006082893189-PCT00028
 여기에서 m은 0 내지 3의 정수이고, R13은 수소, 할로겐, 하이드록시, (C1-C6)-알킬, (C3-C7)-사이클로알킬, (C6-C10)-아릴, (C1-C9)헤테로아릴, (C2-C9)-헤테로사이클릴, O-(C1-C6)-알킬, O-(C3-C7)-사이클로알킬, SO2-(C1-C6)알킬, SO2(C3-C7)-사이클로알킬, NHSO2(C1-C6)알킬, N((C1-C6)알킬)(SO2(C1-C6-알킬)), N((C3-C7)사이클로 알킬(SO2(C1-C6-알킬)), N(C1-C6-알킬)(SO2(C3-C7)사이클로알킬), N((C3-C7)사이클로알킬)(SO2(C3-C7)사이클로알킬), OSO2(C1-C6)알킬, SO2CF3, SO2NH2, SO2NH(C1-C6)알킬, SO2NH(C3-C7)사이클로알킬, SO2NR5R6, SO2N((C1-C6)알킬)2, CF3, CO-(C1-C6)알킬, CO-(C3-C7)사이클로알킬, COCF3, CO2(C1-C6)알킬,
Figure 112006082893189-PCT00029
및
Figure 112006082893189-PCT00030
로 구성된 군으로부터 선택된 치환체이다.Where m is an integer from 0 to 3, R 13 is hydrogen, halogen, hydroxy, (C 1 -C 6 ) -alkyl, (C 3 -C 7 ) -cycloalkyl, (C 6 -C 10 )- Aryl, (C 1 -C 9 ) heteroaryl, (C 2 -C 9 ) -heterocyclyl, O- (C 1 -C 6 ) -alkyl, O- (C 3 -C 7 ) -cycloalkyl, SO 2- (C 1 -C 6 ) alkyl, SO 2 (C 3 -C 7 ) -cycloalkyl, NHSO 2 (C 1 -C 6 ) alkyl, N ((C 1 -C 6 ) alkyl) (SO 2 ( C 1 -C 6 -alkyl)), N ((C 3 -C 7 ) cycloalkyl (SO 2 (C 1 -C 6 -alkyl)), N (C 1 -C 6 -alkyl) (SO 2 (C 3 -C 7 ) cycloalkyl), N ((C 3 -C 7 ) cycloalkyl) (SO 2 (C 3 -C 7 ) cycloalkyl), OSO 2 (C 1 -C 6 ) alkyl, SO 2 CF 3 , SO 2 NH 2 , SO 2 NH (C 1 -C 6 ) alkyl, SO 2 NH (C 3 -C 7 ) cycloalkyl, SO 2 NR 5 R 6 , SO 2 N ((C 1 -C 6 ) alkyl ) 2 , CF 3 , CO- (C 1 -C 6 ) alkyl, CO- (C 3 -C 7 ) cycloalkyl, COCF 3 , CO 2 (C 1 -C 6 ) alkyl,
Figure 112006082893189-PCT00029
And
Figure 112006082893189-PCT00030
Substituent selected from the group consisting of. 제 1 항 내지 6 항 중의 어느 한 항에 있어서, 하기 화학식 3으로 표시되는 화합물.The compound according to any one of claims 1 to 6, represented by the following formula (3). [화학식 3][Formula 3]
Figure 112006082893189-PCT00031
Figure 112006082893189-PCT00031
 상기 식에서, B는 하기 화학식의 기들로 구성된 군으로부터 선택된다:Wherein B is selected from the group consisting of groups of the formula:
Figure 112006082893189-PCT00032
Figure 112006082893189-PCT00032
 제 1 항 내지 7 항 중의 어느 한 항에 있어서, 하기 화학식 4로 표시되는 화합물.The compound according to any one of claims 1 to 7, represented by the following general formula (4). [화학식 4][Formula 4]
Figure 112006082893189-PCT00033
Figure 112006082893189-PCT00033
 상기 식에서, D는 하기 화학식의 기들로 구성된 군으로부터 선택되며,Wherein D is selected from the group consisting of groups of the formula
Figure 112006082893189-PCT00034
Figure 112006082893189-PCT00034
Figure 112006082893189-PCT00035
Figure 112006082893189-PCT00035
 여기에서 q는 1 내지 2의 정수이다.Q is an integer of 1 to 2 here. 제 1 항 내지 8 항 중의 어느 한 항에 있어서, 하기 화학식 5로 표시되는 화합물.The compound according to any one of claims 1 to 8, represented by the following formula (5). [화학식 5][Formula 5]
Figure 112006082893189-PCT00036
Figure 112006082893189-PCT00036
 상기 식에서, E는 하기 화학식의 기로 구성된 군으로부터 선택되며,Wherein E is selected from the group consisting of groups of the formula
Figure 112006082893189-PCT00037
Figure 112006082893189-PCT00037
 여기에서 R14는 (C1-C6)-알킬, (C3-C7)-사이클로알킬 및 (C2-C9)-헤테로사이클릴로 구성된 군으로부터 선택되고, R15는 수소, (C1-C6)-알킬, (C3-C7)-사이클로알킬 및 (C2-C9)-헤테로사이클릴로 구성된 군으로부터 선택된다.Where R 14 is (C 1 -C 6) - alkyl, (C 3 -C 7) - cycloalkyl and (C 2 -C 9) - is selected from the group consisting of heterocycle reels, R 15 is hydrogen, (C 1 -C 6 ) -alkyl, (C 3 -C 7 ) -cycloalkyl and (C 2 -C 9 ) -heterocyclyl. N-메틸-N-{3-[({메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노})-메틸]-페닐}-메탄설폰아미드;N-methyl-N- {3-[({methyl- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino})-methyl] -phenyl} -methanesulfonamide; N-메틸-N-{4-메틸-3-[({메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]아미노})-메틸]-페닐}-메탄설폰아미드;N-methyl-N- {4-methyl-3-[({methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl- Pyrimidin-4-yl] amino})-methyl] -phenyl} -methanesulfonamide; N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide; N-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide; N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide; N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (2-Methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide; 5-[4-(3-메탄설포닐-프로필아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (3-methanesulfonyl-propylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one; N-메틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide; N-(3-메탄설포닐아미노아미노-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N- (3-methanesulfonylaminoamino-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide; N-메틸-N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-methyl-N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide; N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide; N-메틸-N-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-Methyl-N- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide; 5-{4-[((1S,2R)-2-하이드록시-사이클로헥실메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[((1S, 2R) -2-hydroxy-cyclohexylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole 2-one; 5-[4-((1R,2S)-2-하이드록시-인단-1-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((1R, 2S) -2-hydroxy-indan-1-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole- 2-one; 5-[4-((S)-1-하이드록시메틸-2-페닐-에틸아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((S) -1-hydroxymethyl-2-phenyl-ethylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole-2 -On; N-(3-메탄설포닐-메틸-아미노)-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (3-methanesulfonyl-methyl-amino) -5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyri Midin-4-ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide; 5-{4-[(1-하이드록시-사이클로펜틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-hydroxy-cyclopentylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one; N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide; N-(3-플루오로-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (3-fluoro-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide; 5-{4-[2-((S)-1-메탄설포닐-피롤리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2-((S) -1-Methanesulfonyl-pyrrolidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one; 5-{4-[(1-하이드록시-사이클로부틸메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(1-hydroxy-cyclobutylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indol-2-one; 5-{4-[2-((R)-1-메탄설포닐-피롤리딘-2-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2-((R) -1-methanesulfonyl-pyrrolidin-2-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1, 3-dihydro-indol-2-one; N-(2-플루오로-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (2-Fluoro-6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide; N-(4-플루오로-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (4-fluoro-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -N-methyl-methanesulfonamide; N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오 로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide; N-{2,2-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-N-메틸-메탄설폰아미드;N- {2,2-dimethyl-3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -N-methyl-methanesulfonamide; N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide; N-(2,4-디플루오로-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-N-메틸-메탄설폰아미드;N- (2,4-difluoro-6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -N-methyl-methanesulfonamide; 5-[4-((R)-1-메탄설포닐-피페리딘-3-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((R) -1-methanesulfonyl-piperidin-3-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indole 2-one; N-메틸-N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide; 5-[4-(1-메탄설포닐-피페리딘-4-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (1-Methanesulfonyl-piperidin-4-ylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one ; 5-{4-[메틸-((R)-1-페닐-에틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [Methyl-((R) -1-phenyl-ethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2- On; 5-(4-벤질아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-benzylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one; N-(4,6-디메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플 루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-N-메틸-메탄설폰아미드;N- (4,6-dimethyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amino] -methyl} -pyridin-2-yl) -N-methyl-methanesulfonamide; 5-(4-tert-부틸아미노-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-tert-butylamino-5-trifluoromethyl-pyrimidin-2-ylamino) -1,3-dihydro-indol-2-one; 5-[4-((1R,5S,6S)-3-메탄설포닐-3-아자-비사이클로[3.1.0]헥스-6-일아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4-((1R, 5S, 6S) -3-methanesulfonyl-3-aza-bicyclo [3.1.0] hex-6-ylamino) -5-trifluoromethyl-pyrimidine-2 -Ylamino] -1,3-dihydro-indol-2-one; N-메틸-N-{3-메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-부틸}-메탄설폰아미드;N-Methyl-N- {3-methyl-3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -butyl} -methanesulfonamide; N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N- (6-Methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide; 5-{4-[(2-메탄설포닐-피리딘-4-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-methanesulfonyl-pyridin-4-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole-2 -On; 2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 아미드;2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid amide; N-(3-{메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노}-프로필)-메탄설폰아미드;N- (3- {methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -amino} -Propyl) -methanesulfonamide; N-(2-{메틸-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일]-아미노}-에틸)-메탄설폰아미드;N- (2- {methyl- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl] -amino} -Ethyl) -methanesulfonamide; 5-[4-(2-메탄설포닐메틸-벤질아미노)-5-트리플루오로메틸-피리미딘-2-일아미노]-1,3-디하이드로-인돌-2-온;5- [4- (2-methanesulfonylmethyl-benzylamino) -5-trifluoromethyl-pyrimidin-2-ylamino] -1,3-dihydro-indol-2-one; 2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리 미딘-4-일아미노]-에탄설폰산 디메틸아미드;2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid dimethylamide; N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrazin-2-yl) -methanesulfonamide; 에탄설폰산 메틸-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Methyl ethanesulfonic acid- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -phenyl) -amide; 에탄설폰산 (2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -methyl} -Phenyl) -amide; N-에틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-ethyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -methanesulfonamide; N-{1,1-디메틸-3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;N- {1,1-dimethyl-3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide; N-(5,6-디메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-N-메틸-메탄설폰아미드;N- (5,6-dimethyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-yl Amino] -methyl} -pyrazin-2-yl) -N-methyl-methanesulfonamide; 5-{4-[((R)-4-메탄설포닐-모르폴린-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[((R) -4-methanesulfonyl-morpholin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-di Hydro-indol-2-ones; 프로판-1-설폰산 (2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Propane-1-sulfonic acid (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -amide; 5-{4-[2-((R)-4-메탄설포닐-모르폴린-3-일)-에틸아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4- [2-((R) -4-methanesulfonyl-morpholin-3-yl) -ethylamino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3 -Dihydro-indol-2-one; 에탄설폰산 메틸-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-아미드;Methane-ethanesulfonic acid- (3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-2-yl) -amide; 트리플루오로-N-메틸-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;Trifluoro-N-methyl-N- {3- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Ylamino] -propyl} -methanesulfonamide; 사이클로프로판설폰산 메틸-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;Cyclopropanesulfonic acid methyl- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Propyl} -amide; N-에틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-ethyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -phenyl) -methanesulfonamide; 에탄설폰산 메틸-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Methane-ethanesulfonic acid- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide; 에탄설폰산 에틸-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid ethyl- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino]- Methyl} -phenyl) -amide; 에탄설폰산 에틸-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid ethyl- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4- Monoamino] -methyl} -phenyl) -amide; N-에틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-ethyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -methanesulfonamide; 에탄설폰산 (5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -amide; 에탄설폰산 (3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Ethanesulfonic acid (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -amide; 에탄설폰산 메틸-(3-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미 노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-아미드;Methane-ethanesulfonic acid- (3-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -phenyl) -amide; 2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에탄설폰산 메틸아미드;2- [2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethanesulfonic acid methylamide; 에탄설폰산 {3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;Ethanesulfonic acid {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -propyl}- amides; C-메탄설포닐-N-{3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-메탄설폰아미드;C-methanesulfonyl-N- {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Propyl} -methanesulfonamide; 에탄설폰산 {2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-아미드;Ethanesulfonic acid {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -ethyl}- amides; C-메탄설포닐-N-{2-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-에틸}-메탄설폰아미드;C-methanesulfonyl-N- {2- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Ethyl} -methanesulfonamide; N-메틸-N-(4-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (4-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; 5-(4-{[1-(2,2,2-트리플루오로-아세틸)-피페리딘-3-일메틸]-아미노}-5-트리플루오로메틸-피리미딘-2-일아미노)-1,3-디하이드로-인돌-2-온;5- (4-{[1- (2,2,2-Trifluoro-acetyl) -piperidin-3-ylmethyl] -amino} -5-trifluoromethyl-pyrimidin-2-ylamino ) -1,3-dihydro-indol-2-one; 2,2,2-트리플루오로-에탄설폰산 {3-[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-프로필}-아미드;2,2,2-trifluoro-ethanesulfonic acid {3- [2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine -4-ylamino] -propyl} -amide; N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-2-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-2-yl) -methanesulfonamide; N-사이클로프로필-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5- 트리플루오로메틸-피리미딘-4-일아미노]-메틸}-페닐)-메탄설폰아미드;N-cyclopropyl-N- (2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -phenyl) -methanesulfonamide; N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrazin-2-yl) -methanesulfonamide; N-메틸-N-(2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-4-일)-메탄설폰아미드;N-methyl-N- (3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-4-yl) -methanesulfonamide; N-사이클로프로필-N-(3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-cyclopropyl-N- (3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino ] -Methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(6-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide; 5-{4-[(2-메탄설포닐메틸-피리딘-3-일메틸)-아미노]-5-트리플루오로메틸-피리미딘-2-일아미노}-1,3-디하이드로-인돌-2-온;5- {4-[(2-Methanesulfonylmethyl-pyridin-3-ylmethyl) -amino] -5-trifluoromethyl-pyrimidin-2-ylamino} -1,3-dihydro-indole- 2-one; N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(3-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (3-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(5-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(4-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (4-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(2-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (2-methyl-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(5-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(6-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (6-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(5-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (5-methyl-2-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(4-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (4-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(3-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-methyl-N- (3-methyl-4-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(5-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-2-yl) -methanesulfonamide; N-메틸-N-(6-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-5-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(6-메틸-2-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (6-methyl-2-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(5-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(2-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-4-일)-메탄설폰아미드;N-Methyl-N- (2-methyl-3-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-4-yl) -methanesulfonamide; N-메틸-N-(6-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-2-yl) -methanesulfonamide; N-메틸-N-(5-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-4-일)-메탄설폰아미드;N-methyl-N- (5-methyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-4-yl) -methanesulfonamide; N-메틸-N-(5-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(5-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (6-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(6-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-2-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-2-yl) -methanesulfonamide; N-메틸-N-(2-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-methyl-N- (2-methyl-4-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(6-메틸-4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리딘-3-일)-메탄설폰아미드;N-Methyl-N- (6-methyl-4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyridin-3-yl) -methanesulfonamide; N-메틸-N-(4-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-5-일)-메탄설폰아미드;N-methyl-N- (4-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidin-4-ylamino] -Methyl} -pyrimidin-5-yl) -methanesulfonamide; N-메틸-N-(2-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드;N-methyl-N- (2-methyl-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide; N-메틸-N-(4-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-5-일)-메탄설폰아미드;N-Methyl-N- (4-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-5-yl) -methanesulfonamide; N-메틸-N-(5-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-Methyl-N- (5-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide; N-메틸-N-(5-메틸-3-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드;N-methyl-N- (5-methyl-3-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide; N-메틸-N-(2-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-5-일)-메탄설폰아미드;N-Methyl-N- (2-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-5-yl) -methanesulfonamide; N-메틸-N-(3-메틸-6-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트 리플루오로메틸-피리미딘-4-일아미노]-메틸}-피라진-2-일)-메탄설폰아미드; 및N-Methyl-N- (3-methyl-6-{[2- (2-oxo-2,3-dihydro-1 H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine- 4-ylamino] -methyl} -pyrazin-2-yl) -methanesulfonamide; And N-메틸-N-(6-메틸-5-{[2-(2-옥소-2,3-디하이드로-1H-인돌-5-일아미노)-5-트리플루오로메틸-피리미딘-4-일아미노]-메틸}-피리미딘-4-일)-메탄설폰아미드N-methyl-N- (6-methyl-5-{[2- (2-oxo-2,3-dihydro-1H-indol-5-ylamino) -5-trifluoromethyl-pyrimidine-4 -Ylamino] -methyl} -pyrimidin-4-yl) -methanesulfonamide 로 구성된 군으로부터 선택되는 화합물.Compound selected from the group consisting of. 비정상적인 세포성장을 치료하는데 효과적인 양의 제 1 항의 화합물을 포유동물에게 투여하는 것을 포함하는, 포유동물에서 비정상적인 세포성장을 치료하는 방법.A method of treating abnormal cell growth in a mammal comprising administering to the mammal an amount of the compound of claim 1 effective to treat abnormal cell growth. 비정상적인 세포성장을 치료하는데 효과적인 양의 제 1 항의 화합물, 및 약제학적으로 허용되는 담체를 포함하는, 포유동물에서 비정상적인 세포성장을 치료하기 위한 약제학적 조성물.A pharmaceutical composition for treating abnormal cell growth in a mammal, comprising an amount of the compound of claim 1 effective to treat abnormal cell growth, and a pharmaceutically acceptable carrier.
KR1020067023767A 2004-05-14 2005-05-02 Pyrimidine derivatives for the treatment of abnormal cell growth KR100886990B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US57131204P 2004-05-14 2004-05-14
US60/571,312 2004-05-14
PCT/IB2005/001201 WO2005111023A1 (en) 2004-05-14 2005-05-02 Pyrimidine derivatives for the treatment of abnormal cell growth

Publications (2)

Publication Number Publication Date
KR20070012477A true KR20070012477A (en) 2007-01-25
KR100886990B1 KR100886990B1 (en) 2009-03-04

Family

ID=34966230

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020067023767A KR100886990B1 (en) 2004-05-14 2005-05-02 Pyrimidine derivatives for the treatment of abnormal cell growth

Country Status (27)

Country Link
EP (1) EP1751143A1 (en)
JP (1) JP4099212B2 (en)
KR (1) KR100886990B1 (en)
CN (2) CN102127058A (en)
AP (1) AP2241A (en)
AR (1) AR049097A1 (en)
AU (2) AU2005243397A1 (en)
BR (1) BRPI0511138A (en)
CA (1) CA2566707A1 (en)
CR (1) CR8749A (en)
EA (1) EA200601796A1 (en)
EC (1) ECSP066997A (en)
GE (1) GEP20104875B (en)
GT (1) GT200500113A (en)
IL (1) IL178828A0 (en)
MA (1) MA28583B1 (en)
MX (1) MXPA06011890A (en)
NL (2) NL1029045C2 (en)
NO (1) NO20064576L (en)
NZ (1) NZ550448A (en)
PA (1) PA8632601A1 (en)
PE (1) PE20060240A1 (en)
TN (1) TNSN06370A1 (en)
TW (1) TWI303635B (en)
UY (1) UY28894A1 (en)
WO (1) WO2005111023A1 (en)
ZA (1) ZA200608394B (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2566531A1 (en) * 2004-05-18 2005-12-15 Rigel Pharmaceuticals, Inc. Cycloalkyl substituted pyrimidinediamine compounds and their uses
US20070032514A1 (en) * 2005-07-01 2007-02-08 Zahn Stephan K 2,4-diamino-pyrimidines as aurora inhibitors
AU2006327871A1 (en) * 2005-12-21 2007-06-28 Pfizer Products Inc. Pyrimidine derivatives for the treatment of abnormal cell growth
MX2009011090A (en) * 2007-04-18 2009-11-02 Pfizer Prod Inc Sulfonyl amide derivatives for the treatment of abnormal cell growth.
KR20100049068A (en) * 2007-07-17 2010-05-11 리겔 파마슈티칼스, 인크. Cyclic amine substituted pyrimidinediamines as pkc inhibitors
WO2009071535A1 (en) * 2007-12-03 2009-06-11 Boehringer Ingelheim International Gmbh Diaminopyridines for the treatment of diseases which are characterised by excessive or anomal cell proliferation
CA2723961C (en) * 2008-05-21 2017-03-21 Ariad Pharmaceuticals, Inc. Phosphorous derivatives as kinase inhibitors
US8410126B2 (en) * 2009-05-29 2013-04-02 Boehringer Ingelheim International Gmbh Pyrimidine inhibitors of PKTK2
US8933227B2 (en) 2009-08-14 2015-01-13 Boehringer Ingelheim International Gmbh Selective synthesis of functionalized pyrimidines
JP5539518B2 (en) 2009-08-14 2014-07-02 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Regioselective preparation of 2-amino-5-trifluoromethylpyrimidine derivatives
US20120244141A1 (en) 2010-09-28 2012-09-27 Boehringer Ingelheim International Gmbh Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors
WO2014174745A1 (en) * 2013-04-26 2014-10-30 国立大学法人京都大学 Eg5 INHIBITOR
CN109608444B (en) * 2018-11-27 2022-02-11 中国药科大学 Isoindolinone-containing ERK inhibitor and preparation method and application thereof
CN111732548B (en) * 2020-06-11 2022-06-17 浙江大学 N2-carbamyl aromatic ring-2-aminopyrimidine derivatives and medical application thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9721437D0 (en) * 1997-10-10 1997-12-10 Glaxo Group Ltd Heteroaromatic compounds and their use in medicine
AR042586A1 (en) 2001-02-15 2005-06-29 Sugen Inc 3- (4-AMIDOPIRROL-2-ILMETILIDEN) -2-INDOLINONE AS INHIBITORS OF PROTEIN KINASE; YOUR PHARMACEUTICAL COMPOSITIONS; A METHOD FOR THE MODULATION OF THE CATALYTIC ACTIVITY OF PROTEINQUINASE; A METHOD TO TREAT OR PREVENT AN AFFECTION RELATED TO PROTEINQUINASE
WO2003030909A1 (en) * 2001-09-25 2003-04-17 Bayer Pharmaceuticals Corporation 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer
UA80767C2 (en) * 2002-12-20 2007-10-25 Pfizer Prod Inc Pyrimidine derivatives for the treatment of abnormal cell growth
WO2004056807A1 (en) * 2002-12-20 2004-07-08 Pfizer Products Inc. Pyrimidine derivatives for the treatment of abnormal cell growth

Also Published As

Publication number Publication date
NL1029045C2 (en) 2006-06-02
AP2241A (en) 2011-06-01
PA8632601A1 (en) 2006-06-02
EA200601796A1 (en) 2007-04-27
NL1031845A1 (en) 2006-07-31
ECSP066997A (en) 2007-02-28
CA2566707A1 (en) 2005-11-24
PE20060240A1 (en) 2006-04-01
GT200500113A (en) 2006-01-10
UY28894A1 (en) 2005-12-30
JP2007537234A (en) 2007-12-20
KR100886990B1 (en) 2009-03-04
JP4099212B2 (en) 2008-06-11
GEP20104875B (en) 2010-01-11
NO20064576L (en) 2006-11-07
MXPA06011890A (en) 2006-12-14
ZA200608394B (en) 2008-05-28
AP2006003790A0 (en) 2006-10-31
NZ550448A (en) 2010-11-26
MA28583B1 (en) 2007-05-02
AR049097A1 (en) 2006-06-28
NL1029045A1 (en) 2005-11-15
CR8749A (en) 2006-12-05
TWI303635B (en) 2008-12-01
NL1031845C2 (en) 2006-11-23
CN1953974A (en) 2007-04-25
CN102127058A (en) 2011-07-20
TNSN06370A1 (en) 2008-02-22
AU2005243397A1 (en) 2005-11-24
WO2005111023A1 (en) 2005-11-24
BRPI0511138A (en) 2007-11-27
TW200539871A (en) 2005-12-16
AU2009238255A1 (en) 2009-12-03
EP1751143A1 (en) 2007-02-14
IL178828A0 (en) 2007-03-08

Similar Documents

Publication Publication Date Title
KR100886990B1 (en) Pyrimidine derivatives for the treatment of abnormal cell growth
US7109337B2 (en) Pyrimidine derivatives for the treatment of abnormal cell growth
EP1625121B1 (en) Pyrimidine derivatives for the treatment of abnormal cell growth
KR101060051B1 (en) Pyrimidine Derivatives to Treat Abnormal Cell Growth
US7208499B2 (en) Pyrimidine derivatives for the treatment of abnormal cell growth
US7145008B2 (en) Pyrimidine derivatives for the treatment of abnormal cell growth
US20060205945A1 (en) Pyrimidine derivatives for the treatment of abnormal cell growth

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
E90F Notification of reason for final refusal
E701 Decision to grant or registration of patent right
GRNT Written decision to grant
FPAY Annual fee payment

Payment date: 20130305

Year of fee payment: 5

FPAY Annual fee payment

Payment date: 20140211

Year of fee payment: 6

FPAY Annual fee payment

Payment date: 20150224

Year of fee payment: 7

FPAY Annual fee payment

Payment date: 20160211

Year of fee payment: 8

FPAY Annual fee payment

Payment date: 20170221

Year of fee payment: 9

FPAY Annual fee payment

Payment date: 20180221

Year of fee payment: 10

FPAY Annual fee payment

Payment date: 20190212

Year of fee payment: 11

FPAY Annual fee payment

Payment date: 20200214

Year of fee payment: 12