KR20130115696A - Urea analogs as neuroprotective agents - Google Patents
Urea analogs as neuroprotective agents Download PDFInfo
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- KR20130115696A KR20130115696A KR1020120038239A KR20120038239A KR20130115696A KR 20130115696 A KR20130115696 A KR 20130115696A KR 1020120038239 A KR1020120038239 A KR 1020120038239A KR 20120038239 A KR20120038239 A KR 20120038239A KR 20130115696 A KR20130115696 A KR 20130115696A
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- JDIPNDGYSHYUHJ-UHFFFAOYSA-N CC(C)(C)NC(Nc(nccc1)c1OCc1cccc(F)c1)=O Chemical compound CC(C)(C)NC(Nc(nccc1)c1OCc1cccc(F)c1)=O JDIPNDGYSHYUHJ-UHFFFAOYSA-N 0.000 description 1
- DBBWIBFRWQTQIA-UHFFFAOYSA-N CC(C)NC(Nc(nccc1)c1OCc1ccccc1)=S Chemical compound CC(C)NC(Nc(nccc1)c1OCc1ccccc1)=S DBBWIBFRWQTQIA-UHFFFAOYSA-N 0.000 description 1
- LSHDVACGODZUFF-UHFFFAOYSA-N CCNC(Nc1ncccc1OCc1cc(F)ccc1)=O Chemical compound CCNC(Nc1ncccc1OCc1cc(F)ccc1)=O LSHDVACGODZUFF-UHFFFAOYSA-N 0.000 description 1
- SLHFTSROMBTURZ-UHFFFAOYSA-N CNC(Nc(nccc1)c1OCc1ccccc1Cl)=O Chemical compound CNC(Nc(nccc1)c1OCc1ccccc1Cl)=O SLHFTSROMBTURZ-UHFFFAOYSA-N 0.000 description 1
- WICRURHTJKGIEQ-UHFFFAOYSA-N Cc(cc1)ccc1NC(Nc(nccc1)c1OCc1ccccc1Cl)=O Chemical compound Cc(cc1)ccc1NC(Nc(nccc1)c1OCc1ccccc1Cl)=O WICRURHTJKGIEQ-UHFFFAOYSA-N 0.000 description 1
- NLRYVYDRXHPHRW-UHFFFAOYSA-N Cc(cc1)ccc1NC(Nc(nccn1)c1OCc(cc1)ccc1Cl)=O Chemical compound Cc(cc1)ccc1NC(Nc(nccn1)c1OCc(cc1)ccc1Cl)=O NLRYVYDRXHPHRW-UHFFFAOYSA-N 0.000 description 1
- PUYHZUNALXCKLU-UHFFFAOYSA-N Fc1cc(COc2c(NC(Nc3cccc(Cl)c3)=S)nccc2)ccc1 Chemical compound Fc1cc(COc2c(NC(Nc3cccc(Cl)c3)=S)nccc2)ccc1 PUYHZUNALXCKLU-UHFFFAOYSA-N 0.000 description 1
- JKGGFJLWYSMZKF-UHFFFAOYSA-N O=C(NC1CCCCCC1)Nc(nccc1)c1OCc1ccccc1Cl Chemical compound O=C(NC1CCCCCC1)Nc(nccc1)c1OCc1ccccc1Cl JKGGFJLWYSMZKF-UHFFFAOYSA-N 0.000 description 1
- QJUOCVYWLAMSRN-UHFFFAOYSA-N O=C(NC1CCCCCC1)Nc(nccn1)c1OCc(cc1)ccc1F Chemical compound O=C(NC1CCCCCC1)Nc(nccn1)c1OCc(cc1)ccc1F QJUOCVYWLAMSRN-UHFFFAOYSA-N 0.000 description 1
- SCBBSGKITKCIFE-UHFFFAOYSA-N O=C(NC1CCCCCC1)Nc(nccn1)c1OCc1cccc(F)c1 Chemical compound O=C(NC1CCCCCC1)Nc(nccn1)c1OCc1cccc(F)c1 SCBBSGKITKCIFE-UHFFFAOYSA-N 0.000 description 1
- BHGUTPRVUIIKRD-UHFFFAOYSA-N O=C(NC1CCCCCC1)Nc1ncc[n]c1OCc1cccc(Cl)c1 Chemical compound O=C(NC1CCCCCC1)Nc1ncc[n]c1OCc1cccc(Cl)c1 BHGUTPRVUIIKRD-UHFFFAOYSA-N 0.000 description 1
- YEORIFQYWAMHQI-UHFFFAOYSA-N O=C(NCCCl)Nc(nccc1)c1OCc(cc1)ccc1Cl Chemical compound O=C(NCCCl)Nc(nccc1)c1OCc(cc1)ccc1Cl YEORIFQYWAMHQI-UHFFFAOYSA-N 0.000 description 1
- VZQZLNKCEFGWCJ-UHFFFAOYSA-N O=C(NCCN1CCNCC1)Nc(nccc1)c1OCc1ccccc1Cl Chemical compound O=C(NCCN1CCNCC1)Nc(nccc1)c1OCc1ccccc1Cl VZQZLNKCEFGWCJ-UHFFFAOYSA-N 0.000 description 1
- DAEFTAVMIHGPEO-UHFFFAOYSA-N O=C(NCc1ccccc1)Nc(nccc1)c1OCc1cccc(Cl)c1 Chemical compound O=C(NCc1ccccc1)Nc(nccc1)c1OCc1cccc(Cl)c1 DAEFTAVMIHGPEO-UHFFFAOYSA-N 0.000 description 1
- GTHLFZUWKDRAPL-UHFFFAOYSA-N O=C(Nc(cc1Cl)ccc1Cl)Nc(nccc1)c1OCc1cccc(Cl)c1 Chemical compound O=C(Nc(cc1Cl)ccc1Cl)Nc(nccc1)c1OCc1cccc(Cl)c1 GTHLFZUWKDRAPL-UHFFFAOYSA-N 0.000 description 1
- RMRCNFZSWJEHDS-UHFFFAOYSA-N O=C(Nc(cc1Cl)ccc1Cl)Nc(nccc1)c1OCc1ccccc1Cl Chemical compound O=C(Nc(cc1Cl)ccc1Cl)Nc(nccc1)c1OCc1ccccc1Cl RMRCNFZSWJEHDS-UHFFFAOYSA-N 0.000 description 1
- GULVIFPDZSAEQB-UHFFFAOYSA-N O=C(Nc(cccc1)c1F)Nc(nccc1)c1OCc1ccccc1 Chemical compound O=C(Nc(cccc1)c1F)Nc(nccc1)c1OCc1ccccc1 GULVIFPDZSAEQB-UHFFFAOYSA-N 0.000 description 1
- OKJMGIKSKUXFRV-UHFFFAOYSA-N O=C(Nc1cccc(F)c1)Nc(nccc1)c1OCc1ccccc1 Chemical compound O=C(Nc1cccc(F)c1)Nc(nccc1)c1OCc1ccccc1 OKJMGIKSKUXFRV-UHFFFAOYSA-N 0.000 description 1
- CZPDYZXWKZDPOQ-UHFFFAOYSA-N O=C(Nc1cccc(F)c1)Nc(nccn1)c1OCc1cccc(F)c1 Chemical compound O=C(Nc1cccc(F)c1)Nc(nccn1)c1OCc1cccc(F)c1 CZPDYZXWKZDPOQ-UHFFFAOYSA-N 0.000 description 1
- CURJVQJGTFVFCJ-UHFFFAOYSA-N O=C(Nc1cccc2c1cccc2)Nc(nccn1)c1OCc1cccc(F)c1 Chemical compound O=C(Nc1cccc2c1cccc2)Nc(nccn1)c1OCc1cccc(F)c1 CURJVQJGTFVFCJ-UHFFFAOYSA-N 0.000 description 1
- LABKTFFQMIAICI-UHFFFAOYSA-N S=C(Nc1cccc(Cl)c1)Nc(nccc1)c1OCc1ccccc1Cl Chemical compound S=C(Nc1cccc(Cl)c1)Nc(nccc1)c1OCc1ccccc1Cl LABKTFFQMIAICI-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
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Abstract
Description
본 발명은 미토콘드리아에 작용하여 신경보호제로서 약학적 활성을 보이는 유레아 유도체 또는 이의 약제적으로 허용가능한 염, 이들 화합물의 제조방법, 그리고 이들 화합물이 유효성분으로 함유된 약학조성물에 관한 것이다.The present invention relates to urea derivatives or pharmaceutically acceptable salts thereof, which act on mitochondria and exhibit pharmacological activity as neuroprotective agents, methods for preparing these compounds, and pharmaceutical compositions containing these compounds as active ingredients.
알츠하이머병(Alzheimer's disease)은 대표적인 중추신경계 퇴행성 뇌질환으로 기억력, 사고력, 이해력, 계산력, 언어능력, 학습력 그리고 판단력이 점차 감소하여 환자가 치매에 이르게 되는 질병이다. 알츠하이머병의 호발 연령은 65세 이후이나 드물게 40~50대에서도 발생하며, 65세에서 85세 범위에서는 나이가 5세 증가할 때마다 발병률이 2배씩 증가하고, 85세 이상의 경우에는 거의 50%가 이 병에 걸린다고 알려져 있다. 더불어 과학의 발달로 점차 평균 수명이 증가함에 따라 알츠하이머병의 중요성이 두각되고 있다.Alzheimer's disease is a representative neurodegenerative brain disease that causes patients with dementia due to a gradual decrease in memory, thinking, understanding, computation, language, learning and judgment. The prevalence of Alzheimer's disease occurs after age 65, but rarely in the 40s and 50s.In the range of 65 to 85 years, the incidence increases by two times every five years, and nearly 50% of people over 85 years old It is known to have this disease. In addition, the importance of Alzheimer's disease is growing as the life expectancy increases gradually with the development of science.
알츠하이머병은 매우 서서히 발병하여 점진적으로 진행되는 되는 경과가 특징이며, 일단 발병한다면 계속 진행되고 근본적인 치료법이 없으며 연령대별 정상군에 비해 평균 기대수명이 단축된다. 알츠하이머병 초기에는 의욕이 저하되고 기억력이 감소하며, 병이 점차 진행됨에 따라 언어기능, 인지기능의 이상 또는 성격변화, 초조행동, 우울증, 망상, 환각, 공격성 증가, 수면 장애 등의 정신행동 증상이 동반되고, 말기에는 경직, 보행 이상 등 혼자 일상생활을 할 수 없다가 결국에는 대사기능이 떨어져 죽음을 맞이하게 된다.Alzheimer's disease is characterized by a gradual progression that progresses very slowly and, once developed, continues to progress and there is no underlying treatment, and the average life expectancy is shortened compared to normal age groups. In the early stages of Alzheimer's disease, motivation and memory decrease, and as the disease progresses, symptoms of mental behavior such as language function, cognitive function abnormalities or personality changes, anxiety, depression, delusions, hallucinations, increased aggression, and sleep disorders are observed. Accompanying, at the end of the day, such as stiffness, walking abnormalities can not live alone, but eventually the metabolic function falls and die.
이러한 알츠하이머병의 정확한 병인은 아직 밝혀지지 않았으며, 베타 아밀로이드와 같은 신경 독성물질의 축적으로 인한 양측 측두엽의 기능저하로 시작되어 점차 신경세포 밖에 베타 아밀로이드가 쌓여 비정상적으로 뭉쳐있는 특징적인 단백질 덩어리인 노인성 반과 신경세포 안에 비정상적인 타우단백질이 실타래처럼 꼬여 있는 신경섬유매듭 등이 전반적인 뇌의 피질부로 확산되면서 병이 진행된다고 보고되었다. 신경 독성물질인 베타 아밀로이드는 세포막을 관통해 있는 아밀로이드 전구체 단백질이 잘려 36-42개의 아미노산을 포함하는 단백질로써 이러한 베타 아밀로이드는 매우 독성이 있어 적은 양이라도 신경세포들에 손상을 주는 것으로 알려져 있다. 이와 같은 베타 아밀로이드의 독성은 미토콘드리아의 손상과 관계가 있다. The exact etiology of Alzheimer's disease is not yet known, and it begins with the deterioration of the bilateral temporal lobe due to the accumulation of neurotoxic substances such as beta amyloid, and gradually becomes a characteristic protein mass in which abnormally aggregated beta amyloid outside the neurons. It has been reported that the disease progresses as the nerve fiber knot, which is twisted like a skein of abnormal tau protein in half and nerve cells, spreads to the cortex of the general brain. Beta-amyloid, a neurotoxic substance, is a protein containing 36-42 amino acids because the amyloid precursor protein penetrates the cell membrane. These beta-amyloids are known to be very toxic and damage nerve cells even in small amounts. This toxicity of beta amyloid is associated with damage to mitochondria.
미토콘드리아는 산화적 인산화를 통해 ATP (adenosine triphosphate)를 생산하는 세포소기관으로 이의 기능의 변형은 알츠하이머병, 당뇨병, 파킨슨병, 허혈성질환, 헌팅톤병, 정신분열증 등과 같은 질환의 직접 또는 간접적인 원인이 되고 있다. 수용성 베타 아밀로이드는 미토콘드리아에 자리를 잡고 활성화 산소 (수퍼오사이드, 퍼옥시나이트라이트, 하이드록시 라디칼, 과산화소수 등)의 과다 생산을 초래하며 호흡과 ATP 생산을 방해하여 미토콘드리아의 구조에 손상을 주는 것으로 알려져 있다. 미토콘드리아에 대한 베타 아밀로이드의 독성은 세포 내 칼슘의 항상성과 그 신호 전달의 붕괴로 인한 것으로 알려졌으며, 비정상적으로 높은 세포 내 칼슘 농도와 칼슘 신호 기작의 조절 이상은 베타 아밀로이드 플라크 주변의 신경 세포에서 관찰되었다고 보고되었다. 또한 베타 아밀로이드 중합체는 신경 세포에서 대량의 칼슘 유입을 유도하여 미토콘드리아의 칼슘 과부하의 원인이 되고, 궁극적으로 신경 세포의 사멸을 유도한다 [Kroemer et al., FASEB J. 9:1277-87, 1995], [Newmeyer et al., Cell 70:353-64, 1994]. 미토콘드리아의 과부하는 미토콘드리아의 내부 막에 발현된 채널인 mPTP를 개방시켜 미토콘드리아의 작용과 구조를 붕괴시키며, mPTP의 작용을 억제함으로 치매 생쥐모델에서 인지 결합을 향상시키는데 성공하였다고 보고되었다 [Nat. Med. 2008, 1097-1105]. 이러한 연구를 통해 미토콘드리아에 베타 아밀로이드의 축적은 알츠하이머병의 동물모델에서의 미토콘드리아 기능장애와 밀접한 관계가 있다고 증명이 되었으나, 아직까지는 알츠하이머병에서의 미토콘드리아 기능장애를 예방하거나 치료하는 치료법은 개발되지 않은 상황이다. Mitochondria are organelles that produce ATP (adenosine triphosphate) through oxidative phosphorylation, and their alteration of function is a direct or indirect cause of diseases such as Alzheimer's disease, diabetes, Parkinson's disease, ischemic disease, Huntington's disease, and schizophrenia. have. Water-soluble beta amyloid occupies the mitochondria, leads to overproduction of activated oxygen (superoxide, peroxynitrite, hydroxy radicals, hydrogen peroxide, etc.), impairs respiratory and ATP production and damages the structure of mitochondria. Known. Beta amyloid toxicity to mitochondria is known to be due to intracellular calcium homeostasis and disruption of its signal transduction, and abnormally high intracellular calcium concentrations and abnormal control of calcium signaling mechanisms have been observed in neurons around beta amyloid plaques Reported. Beta amyloid polymers also induce large calcium influx in neurons, causing calcium overload in mitochondria and ultimately inducing neuronal death [Kroemer et al., FASEB J. 9: 1277-87, 1995] , Newmeyer et al., Cell 70: 353-64, 1994. Overloading of mitochondria has been reported to open mPTP, a channel expressed in the inner membrane of mitochondria, to disrupt the function and structure of mitochondria, and to inhibit the action of mPTP, thereby improving cognitive binding in demented mouse models [Nat. Med. 2008, 1097-1105. These studies have demonstrated that the accumulation of beta amyloid in mitochondria is closely related to mitochondrial dysfunction in animal models of Alzheimer's disease, but no treatments have been developed to prevent or treat mitochondrial dysfunction in Alzheimer's disease. to be.
본 발명이 이루고자하는 첫 번째 기술적 과제는, mPTP의 작용을 선택적으로 억제하여 미토콘드리아의 기능을 향상시켜 신경보호제로서 약학적 활성을 보이는 유레아 유도체를 제공하는 것이다.The first technical problem to be achieved by the present invention is to provide a urea derivative that exhibits pharmacological activity as a neuroprotective agent by selectively inhibiting the action of mPTP to improve the function of mitochondria.
본 발명이 이루고자 하는 두 번째 기술적 과제는 상기 유레아 유도체의 제조방법을 제공하는 것이다.The second technical problem to be achieved by the present invention is to provide a method for producing the urea derivative.
본 발명이 이루고자 하는 세 번째 기술적 과제는, 상기 유레아 유도체 또는 이의 약제적으로 허용 가능한 염이 유효성분으로 포함되어 있는 약학조성물을 제공하는 것이다.The third technical problem to be achieved by the present invention is to provide a pharmaceutical composition containing the urea derivative or a pharmaceutically acceptable salt thereof as an active ingredient.
상술한 첫 번째 과제를 해결하기 위하여, 본 발명은 하기 화학식 1로 표현되는 유레아 유도체를 제공한다:In order to solve the first problem described above, the present invention provides a urea derivative represented by the following formula (1):
<화학식 1>≪ Formula 1 >
상기 화학식 1에서, In Formula 1,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수조가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one tank of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
상기 두 번째 기술적 과제를 달성하기 위하여, 본 발명은 하기 화학식 2의 화합물과 아이소시아네이트 화합물 또는 아이소티오시아네이트 화합물을 반응시켜 하기 화학식 1의 화합물을 제조하는 단계를 포함하는 유레아 유도체의 제조방법을 제공한다:In order to achieve the second technical problem, the present invention provides a method for preparing a urea derivative comprising the step of preparing a compound of formula 1 by reacting a compound of formula 2 and an isocyanate compound or isothiocyanate compound do:
<화학식 2><Formula 2>
<화학식 1>≪ Formula 1 >
상기 화학식 1, 2에서, In Chemical Formulas 1 and 2,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수조가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one tank of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
본 발명의 일 실시예에 따르면, 상기 화학식 2의 화합물은 하기 화학식 3의 화합물과 벤질할라이드 화합물을 반응시킴으로써 제조될 수 있다:According to an embodiment of the present invention, the compound of Formula 2 may be prepared by reacting a compound of Formula 3 with a benzyl halide compound:
<화학식 3><Formula 3>
상기 화학식 3에서, In Formula 3,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
본 발명의 다른 일 실시예에 따르면, 상기 화학식 2의 화합물은 하기 화학식 4의 화합물과 벤질알콜 화합물을 반응시킴으로써 제조될 수 있다:According to another embodiment of the present invention, the compound of Formula 2 may be prepared by reacting a compound of Formula 4 with a benzyl alcohol compound:
<화학식 4>≪ Formula 4 >
상기 화학식 4에서, In Chemical Formula 4,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
또한, 본 발명의 다른 일 실시예에 따르면, 하기 화학식 5의 화합물과 벤질할라이드 화합물 또는 벤질알콜 화합물을 반응시켜 상기 화학식 1의 화합물을 제조하는 단계를 포함하는 유레아 유도체의 제조방법을 제공한다:In addition, according to another embodiment of the present invention, a method of preparing a urea derivative comprising the step of preparing a compound of Formula 1 by reacting a compound of Formula 5 and a benzyl halide compound or benzyl alcohol compound:
<화학식 5>≪ Formula 5 >
상기 화학식 5에서, In Formula 5,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수조가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one tank of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
본 발명의 또 다른 일 실시예에 따르면, 상기 화학식 5의 화합물은 하기 화학식 3의 화합물과 아이소시아네이트 화합물 또는 아이소티오시아네이트 화합물을 반응시킴으로써 제조될 수 있다:According to another embodiment of the present invention, the compound of Formula 5 may be prepared by reacting a compound of Formula 3 with an isocyanate compound or isothiocyanate compound:
<화학식 3><Formula 3>
상기 화학식 3에서, In Formula 3,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
본 발명의 또 다른 일 실시예에 따르면, 상기 화학식 5의 화합물은 하기 화학식 6의 화합물을 탈벤질화 시킴으로써 제조될 수 있다:According to another embodiment of the present invention, the compound of Formula 5 may be prepared by debenzylating the compound of Formula 6:
<화학식 6>(6)
상기 화학식 6에서, In Formula 6,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수조가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one tank of the ethyl piperazil group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
본 발명의 또 다른 일 실시예에 따르면, 상기 화학식 6의 화합물은 하기 화학식 7의 화합물과 아이소시아네이트 화합물 또는 아이소티오시아네이트 화합물을 반응시켜 제조될 수 있다:According to another embodiment of the present invention, the compound of Formula 6 may be prepared by reacting a compound of Formula 7 with an isocyanate compound or isothiocyanate compound:
<화학식 7>≪ Formula 7 >
상기 화학식 7에서, In Formula 7,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
상기 세 번째 기술적 과제를 달성하기 위하여, 본 발명은 상기 화학식 1로 표시되는 유레아 유도체 또는 이의 약제학적 허용가능한 염을 유효성분으로 포함하는 약학조성물을 제공한다.In order to achieve the third technical problem, the present invention provides a pharmaceutical composition comprising the urea derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 따른 유레아 유도체 또는 이의 약학적으로 허용 가능한 염은 뇌에서 mPTP의 작용을 선택적으로 억제하여 미토콘드리아의 기능을 향상시키는 신경보호제로써 우수한 활성을 나타내며, 알츠하이머병, 파킨슨병, 헌팅톤병, 허혈성 질환, 당뇨병, 정신분열증과 같은 질환의 치료 또는 예방제로 효과를 보인다.The urea derivative according to the present invention or a pharmaceutically acceptable salt thereof has excellent activity as a neuroprotective agent that selectively inhibits the action of mPTP in the brain and improves the function of mitochondria, and is Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic disease. It is effective in the treatment or prevention of diseases such as diabetes, schizophrenia.
본 발명은 하기 화학식 1로 표현되는 유레아 유도체를 제공한다:The present invention provides urea derivatives represented by the following general formula (1):
<화학식 1>≪ Formula 1 >
상기 화학식 1에서, In Formula 1,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수조가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one tank of the ethyl piperazil group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
상기 제 1 알킬기는 메틸, 에틸, 노말프로필기, 아이소프로필기, 노말부틸기, 아이소부틸기, tert-부틸기, 시클로펜틸기, 시클로헥실기로 구성된 군 중에서 선택되는 어느 하나 또는 그 이상일 수 있으며, 상기 알콕시기는 메틸, 에틸, 노말프로필기, 아이소프로필기, 노말부틸기, 아이소부틸기, tert-부틸기, 시클로펜틸기, 시클로헥실기로 구성된 군 중에서 선택된 알킬기가 산소에 연결된 알콕시기일 수 있으나 이에 한정되지는 않고, The first alkyl group may be any one or more selected from the group consisting of methyl, ethyl, normal propyl group, isopropyl group, normal butyl group, isobutyl group, tert- butyl group, cyclopentyl group, cyclohexyl group The alkoxy group may be an alkoxy group in which an alkyl group selected from the group consisting of methyl, ethyl, normal propyl group, isopropyl group, normal butyl group, isobutyl group, tert-butyl group, cyclopentyl group and cyclohexyl group is connected to oxygen. It is not limited to this,
상기 제 2 알킬기는 메틸, 에틸, 노말프로필기, 아이소프로필기, 노말부틸기, 아이소부틸기, tert-부틸기, 시클로부틸기, 시클로펜틸기, 시클로헥실기, 시클로헵틸기, 트리메틸펜틸기, 2,4,4-트리메틸펜틸기로 구성된 군 중에서 선택되는 어느 하나일 수 있으나 이에 한정되지는 않는다. The second alkyl group is preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a normal butyl group, an isobutyl group, a tert-butyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, And a 2,4,4-trimethylpentyl group, but the present invention is not limited thereto.
특히, 바람직한 상기 화학식 1로 표시되는 유레아 화합물을 예시하면 다음과 같다.Particularly, exemplifying the urea compound represented by Chemical Formula 1 is as follows.
화합물 1: 1-(3-(벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;Compound 1: 1- (3- (benzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
화합물 2: 1-(3-(벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;Compound 2: 1- (3- (benzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
화합물 3: 1-(3-(벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 3: 1- (3- (benzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 4: 1-(3-(벤질옥시)피리딘-2-일)-3-벤질 유레아;Compound 4: 1- (3- (benzyloxy) pyridin-2-yl) -3-benzyl urea;
화합물 5: 1-(3-(벤질옥시)피리딘-2-일)-3-페닐 유레아;Compound 5: 1- (3- (benzyloxy) pyridin-2-yl) -3-phenyl urea;
화합물 6: 1-(3-(벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;Compound 6: 1- (3- (benzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
화합물 7: 1-(3-(벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;Compound 7: 1- (3- (benzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 8: 1-(3-(벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 8: 1- (3- (benzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 9: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;Compound 9: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
화합물 10: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;Compound 10: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
화합물 11: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 11: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 12: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-벤질 유레아;Compound 12: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-benzyl urea;
화합물 13: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-페닐 유레아;Compound 13: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-phenyl urea;
화합물 14: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;Compound 14: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
화합물 15: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;Compound 15: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 16: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 16: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 17: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;Compound 17: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
화합물 18: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;Compound 18: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
화합물 19: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 19: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 20: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 20: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 21: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 21: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 22: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;Compound 22: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 23: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;Compound 23: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
화합물 24: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;Compound 24: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
화합물 25: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 25: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 26: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-벤질 유레아;Compound 26: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-benzyl urea;
화합물 27: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-페닐 유레아;Compound 27: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-phenyl urea;
화합물 28: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;Compound 28: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
화합물 29: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 29: 1- (3- (2-Chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 30: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 30: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 31: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;Compound 31: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 32: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;Compound 32: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
화합물 33: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;Compound 33: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
화합물 34: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 34: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 35: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-벤질 유레아;Compound 35: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-benzyl urea;
화합물 36: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-페닐 유레아;Compound 36: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-phenyl urea;
화합물 37: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;Compound 37: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
화합물 38: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 38: l- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 39: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 39: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 40: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;Compound 40: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 41: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;Compound 41: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
화합물 42: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;Compound 42: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
화합물 43: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 43: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 44: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;Compound 44: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
화합물 45: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 45: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 46: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 46: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 47: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;Compound 47: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 48: 1-(3-(벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;Compound 48: 1- (3- (benzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
화합물 49: 1-(3-(벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;Compound 49: 1- (3- (benzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
화합물 50: 1-(3-(벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 50: 1- (3- (benzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 51: 1-(3-(벤질옥시)피리딘-2-일)-3-에틸 유레아;Compound 51: 1- (3- (benzyloxy) pyridin-2-yl) -3-ethyl urea;
화합물 52: 1-(3-(벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;Compound 52: 1- (3- (benzyloxy) pyridin-2-yl) -3-tert-butyl urea;
화합물 53: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;Compound 53: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
화합물 54: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;Compound 54: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
화합물 55: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 55: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 56: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-에틸 유레아;Compound 56: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
화합물 57: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;Compound 57: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
화합물 58: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;Compound 58: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
화합물 59: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 59: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 60: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-에틸 유레아;Compound 60: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
화합물 61: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;Compound 61: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
화합물 62: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;Compound 62: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
화합물 63: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;Compound 63: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
화합물 64: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 64: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 65: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-에틸 유레아;Compound 65: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
화합물 66: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;Compound 66: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
화합물 67: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;Compound 67: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
화합물 68: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;Compound 68: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
화합물 69: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 69: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 70: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-에틸 유레아;Compound 70: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
화합물 71: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;Compound 71: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
화합물 72: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;Compound 72: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
화합물 73: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 73: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 74: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-에틸 유레아;Compound 74: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
화합물 75: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;Compound 75: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
화합물 76: 1-(3-(벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;Compound 76: 1- (3- (benzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
화합물 77: 1-(3-(벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 77: 1- (3- (benzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 78: 1-(3-(벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;Compound 78: 1- (3- (benzyloxy) pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) urea;
화합물 79: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;Compound 79: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
화합물 80: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 80: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 81: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;Compound 81: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) urea;
화합물 82: 1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;Compound 82: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
화합물 83: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;Compound 83: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
화합물 84: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 84: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 85: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;Compound 85: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) urea;
화합물 86: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;Compound 86: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
화합물 87: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 87: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 88: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;Compound 88: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) urea;
화합물 89: 1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;Compound 89: 1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
화합물 90: 1-(3-(벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;Compound 90: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
화합물 91: 1-(3-(벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;Compound 91: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
화합물 92: 1-(3-(벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;Compound 92: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (3,4-difluorophenyl) urea;
화합물 93: 1-(3-(벤질옥시)피라진-2-일)-3-벤질 유레아;Compound 93: 1- (3- (Benzyloxy) pyrazin-2-yl) -3-benzylurea;
화합물 94: 1-(3-(벤질옥시)피라진-2-일)-3-페닐 유레아;Compound 94: 1- (3- (Benzyloxy) pyrazin-2-yl) -3-phenylurea;
화합물 95: 1-(3-(벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;Compound 95: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
화합물 96: 1-(3-(벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;Compound 96: 1- (3- (benzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
화합물 97: 1-(3-(벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;Compound 97: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 98: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;Compound 98: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
화합물 99: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;Compound 99: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
화합물 100: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;Compound 100: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3,4-difluorophenyl) urea;
화합물 101: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-벤질 유레아;Compound 101: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-benzyl urea;
화합물 102: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-페닐 유레아;Compound 102: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-phenyl urea;
화합물 103: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;Compound 103: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
화합물 104: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;Compound 104: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
화합물 105: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;Compound 105: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 106: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;Compound 106: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
화합물 107: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;Compound 107: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
화합물 108: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 108: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 109: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;Compound 109: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
화합물 110: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;Compound 110: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 111: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 111: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 112: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;Compound 112: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
화합물 113: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;Compound 113: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
화합물 114: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;Compound 114: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3,4-difluorophenyl) urea;
화합물 115: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-벤질 유레아;Compound 115: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-benzyl urea;
화합물 116: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-페닐 유레아;Compound 116: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-phenyl urea;
화합물 117: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;Compound 117: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
화합물 118: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;Compound 118: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
화합물 119: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;Compound 119: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 120: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;Compound 120: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
화합물 121: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;Compound 121: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
화합물 122: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;Compound 122: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (3,4-difluorophenyl) urea;
화합물 123: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-벤질 유레아;Compound 123: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-benzyl urea;
화합물 124: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-페닐 유레아;Compound 124: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-phenyl urea;
화합물 125: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;Compound 125: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
화합물 126: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;Compound 126: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
화합물 127: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;Compound 127: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 128: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;Compound 128: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
화합물 129: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;Compound 129: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
화합물 130: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(3,4-다이클로로페닐) 유레아;Compound 130: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (3,4-dichlorophenyl) urea;
화합물 131: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;Compound 131: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
화합물 132: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;Compound 132: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
화합물 133: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;Compound 133: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
화합물 134: 1-(3-(벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;Compound 134: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
화합물 135: 1-(3-(벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;Compound 135: 1- (3- (benzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
화합물 136: 1-(3-(벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 136: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 137: 1-(3-(벤질옥시)피라진-2-일)-3-에틸 유레아;Compound 137: 1- (3- (benzyloxy) pyrazin-2-yl) -3-ethyl urea;
화합물 138: 1-(3-(벤질옥시)피라진-2-일)-3-삼차부틸 유레아;Compound 138: 1- (3- (benzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
화합물 139: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;Compound 139: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
화합물 140: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;Compound 140: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
화합물 141: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 141: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 142: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-에틸 유레아;Compound 142: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
화합물 143: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-삼차부틸 유레아;Compound 143: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
화합물 144: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;Compound 144: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
화합물 145: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 145: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 146: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-에틸 유레아;Compound 146: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
화합물 147: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-삼차부틸 유레아;Compound 147: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
화합물 148: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;Compound 148: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
화합물 149: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;Compound 149: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
화합물 150: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 150: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 151: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-에틸 유레아;Compound 151: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
화합물 152: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-삼차부틸 유레아;Compound 152: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
화합물 153: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;Compound 153: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
화합물 154: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;Compound 154: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
화합물 155: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 155: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 156: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-에틸 유레아;Compound 156: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
화합물 157: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-삼차부틸 유레아;Compound 157: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
화합물 158: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;Compound 158: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
화합물 159: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;Compound 159: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
화합물 160: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-에틸 유레아;Compound 160: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
화합물 161: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-삼차부틸 유레아;Compound 161: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
화합물 162: 1-(3-(벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;Compound 162: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
화합물 163: 1-(3-(벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 163: 1- (3- (benzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 164: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;Compound 164: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
화합물 165: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 165: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 166: 1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;Compound 166: 1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
화합물 167: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;Compound 167: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
화합물 168: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-(피페라진-1-일)에틸) 유레아;Compound 168: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (piperazin-1-yl) ethyl) urea;
화합물 169: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 169: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 170: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;Compound 170: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
화합물 171: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-(피페라진-1-일)에틸) 유레아;Compound 171: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (piperazin-1-yl) ethyl) urea;
화합물 172: 1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;Compound 172: 1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
화합물 173: 1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;Compound 173: 1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
화합물 174: 1-(3-(2-니트로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 174: 1- (3- (2-nitrobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 175: 1-(3-(3-니트로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 175: 1- (3- (3-nitrobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 176: 1-(3-(4-니트로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 176: 1- (3- (4-nitrobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 177: 1-(3-(2-메틸벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 177: 1- (3- (2-methylbenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 178: 1-(3-(3-메틸벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 178: 1- (3- (3-methylbenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 179: 1-(3-(3-메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 179: 1- (3- (3-methoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 180: 1-(3-(2-플루오로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 180: 1- (3- (2-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 181: 1-(3-(3-플루오로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 181: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 182: 1-(3-(4-플루오로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 182: 1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 183: 1-(3-(4-메틸벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 183: 1- (3- (4-methylbenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 184: 1-(3-(4-메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 184: 1- (3- (4-methoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 185: 1-(3-(2-메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 185: 1- (3- (2-methoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 186: 1-(3-(2,4-다이메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 186: 1- (3- (2,4-dimethoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 187: 1-(3-(3,4-다이메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;Compound 187: 1- (3- (3,4-dimethoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
화합물 188: 1-(3-(벤질옥시)피리딘-2-일)-3-에틸 티오유레아;Compound 188: 1- (3- (benzyloxy) pyridin-2-yl) -3-ethyl thiourea;
화합물 189: 1-(3-(벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;Compound 189: 1- (3- (benzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
화합물 190: 1-(3-(벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;Compound 190: 1- (3- (benzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
화합물 191: 1-(3-(벤질옥시)피리딘-2-일)-3-벤질 티오유레아;Compound 191: 1- (3- (benzyloxy) pyridin-2-yl) -3-benzyl thiourea;
화합물 192: 1-(3-(벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;Compound 192: 1- (3- (benzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
화합물 193: 1-(3-(벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;Compound 193: 1- (3- (benzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
화합물 194: 1-(3-(벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;Compound 194: 1- (3- (benzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
화합물 195: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-에틸 티오유레아;Compound 195: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ethyl thiourea;
화합물 196: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;Compound 196: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
화합물 197: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;Compound 197: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
화합물 198: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-벤질 티오유레아;Compound 198: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-benzyl thiourea;
화합물 199: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;Compound 199: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
화합물 200: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;Compound 200: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
화합물 201: 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;Compound 201: 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
화합물 202: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-에틸 티오유레아;Compound 202: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ethyl thiourea;
화합물 203: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;Compound 203: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
화합물 204: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;Compound 204: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
화합물 205: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;Compound 205: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
화합물 206: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;Compound 206: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
화합물 207: 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;Compound 207: 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
화합물 208: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-에틸 티오유레아;Compound 208: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ethyl thiourea;
화합물 209: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;Compound 209: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
화합물 210: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;Compound 210: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
화합물 211: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;Compound 211: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
화합물 212: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;Compound 212: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
화합물 213: 1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;Compound 213: 1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
화합물 214: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-이소프로필 티오유레아;Compound 214: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-isopropyl thiourea;
화합물 215: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-삼차부틸 티오유레아;Compound 215: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-tert-butyl thiourea;
화합물 216: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-벤질 티오유레아;Compound 216: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-benzyl thiourea;
화합물 217: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3-클로로페닐) 티오유레아;Compound 217: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) thiourea;
화합물 218: 1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-ρ-톨릴 티오유레아;Compound 218: 1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl thiourea;
화합물 219: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-이소프로필 티오유레아;Compound 219: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-isopropyl thiourea;
화합물 220: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-벤질 티오유레아;Compound 220: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-benzyl thiourea;
화합물 221: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3-클로로페닐) 티오유레아;Compound 221: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) thiourea;
화합물 222: 1-(3-(2-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 티오유레아;Compound 222: 1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl thiourea;
또한, 본 발명은 상기 두 번째 기술적 과제를 달성하기 위하여, According to another aspect of the present invention,
하기 화학식 2의 화합물과 아이소시아네이트 화합물 또는 아이소티오시아네이트 화합물을 유기용매 하에서 가열 환류 반응시킴으로써 하기 화학식 1의 화합물을 제조하는 단계를 포함하는 유레아 유도체의 제조방법을 제공한다:It provides a method for preparing a urea derivative comprising the step of preparing a compound of formula 1 by heating under reflux reaction of a compound of formula 2 and an isocyanate compound or isothiocyanate compound in an organic solvent:
<화학식 2><Formula 2>
<화학식 1>≪ Formula 1 >
상기 화학식 1 또는 2에서, In the above formula (1) or (2)
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수조가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one tank of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
상기 아이소시아네이트 화합물은 메틸아이소시아네이트, 에틸아이소시아네이트, 프로필아이소시아네이트, 부틸아이소시아네이트, 아이소부틸아이소시아네이트, 2-클로로에틸아이소시아네이트, 트리메틸펜틸아이소시아네이트, 2,4,4-트리메틸펜탄-2-아이소시아네이트, 페닐아이소시아네이트, 할로페닐아이소시아네이트, 디할로페닐아이소시아네이트, 토릴아이소시아네이트, 4-트리플루오로메틸페틸아이소시아네이트, 나프틸아이소시아네이트, 벤질아이소시아네이트, 아다만틸아이소시아네이트, 시클로펜틸아이소시아네이트, 시클로헥실아이소시아네이트, 시클로헵틸아이소시아네이트로 구성된 군 중에서 선택되는 어느 하나일 수 있으며, 상기 아이소티오시아네이트 화합물은 메틸아이소티오시아네이트, 에틸아이소티오시아네이트, 프로필아이소티오시아네이트, 이소프로필아이소티오시아네이트, 부틸아이소티오시아네이트, tert-부틸아이소티오시아네이트, 페닐아이소티오시아네이트, 할로페닐아이소티오시아네이트, 디할로페닐아이소티오시아네이트, 토릴아이소티오시아네이트, 나프틸아이소티오시아네이트, 벤질아이소티오시아네이트로 구성된 군 중에서 선택되는 어느 하나일 수 있으나 이에 한정되지는 않으며, The isocyanate compound is methyl isocyanate, ethyl isocyanate, propyl isocyanate, butyl isocyanate, isobutyl isocyanate, 2-chloroethyl isocyanate, trimethylpentyl isocyanate, 2,4,4-trimethylpentane-2-a Isocyanate, phenyl isocyanate, halophenyl isocyanate, dihalophenyl isocyanate, tolyl isocyanate, 4-trifluoromethylfetyl isocyanate, naphthyl isocyanate, benzyl isocyanate, adamantyl isocyanate, cyclopentyl isocyanate, cyclo Hexyl isocyanate, may be any one selected from the group consisting of cycloheptyl isocyanate, the isothiocyanate compound is methyl isothiocyanate, ethyl isothiocyanate, propyl i Thiocyanate, isopropyl isothiocyanate, butyl isothiocyanate, tert-butyl isothiocyanate, phenyl isothiocyanate, halophenyl isothiocyanate, dihalophenyl isothiocyanate, toryl isothiocia Nate, naphthyl isothiocyanate, benzyl isothiocyanate may be any one selected from the group consisting of, but is not limited thereto,
상기 유기용매는 N,N-디메틸포름아마이드, 아세토니트릴, 테트라하이드로퓨란, 메틸렌클로라이드을 포함하는 군중에서 선택될 수 있으며, 테트라하이드로퓨란이 좀 더 바람직하나 이에 한정되지는 않는다. The organic solvent may be selected from the group comprising N, N-dimethylformamide, acetonitrile, tetrahydrofuran, methylene chloride, tetrahydrofuran is more preferred, but is not limited thereto.
또한, 상기 화학식 1의 화합물은 상기 화학식 2의 화합물과 상기 2-클로로에틸아이소시아네이트의 반응으로 얻어진 화합물을 피페라진 화합물, 피페리딘 화합물, 피롤리딘 화합물로 이루어진 군 중에서 선택되는 어느 하나와 추가 반응시켜 제조된 화합물일 수 있으며,In addition, the compound of Formula 1 is added to the compound obtained by the reaction of the compound of Formula 2 and the 2-chloroethyl isocyanate with any one selected from the group consisting of piperazine compound, piperidine compound, pyrrolidine compound It may be a compound prepared by the reaction,
상기 피페라진 화합물은 피페라진, 메틸피페라진, 에틸피페라진, 에틸메틸피페라진 일 수 있으나 이에 한정되지는 않는다.The piperazine compound may be piperazine, methyl piperazine, ethyl piperazine, ethyl methyl piperazine, but is not limited thereto.
상기 화학식 2의 화합물은 하기 화학식 3의 화합물과 벤질할라이드 화합물을 촉매, 염기 조건 하에서 유기용매에 반응시킴으로써 제조될 수 있다:The compound of Formula 2 may be prepared by reacting a compound of Formula 3 and a benzyl halide compound with an organic solvent under a catalyst and basic conditions:
<화학식 3><Formula 3>
상기 화학식 3에서,In Formula 3,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
상기 촉매는 테트라부틸 암모늄 브로마이드(TBAB) 내지 테트라부틸 포스포튬 브로마이드 (TBPB)를 사용할 수 있으며, 상기 염기는 수산화나트륨 수용액 내지 수산화칼륨 수용액을 사용할 수 있고, 상기 유기용매는 N,N-디메틸포름아마이드, 아세토니트릴, 테트라하이드로퓨란, 메틸렌클로라이드을 포함하는 군중에서 선택될 수 있으며, 메틸렌클로라이드이 좀 더 바람직하나 이에 한정되지는 않는다. The catalyst may be tetrabutylammonium bromide (TBAB) or tetrabutylphosphonium bromide (TBPB). The base may be an aqueous solution of sodium hydroxide or potassium hydroxide, and the organic solvent may be N, N-dimethylformamide , Acetonitrile, tetrahydrofuran, methylene chloride, with methylene chloride being more preferred, but not always limited thereto.
한편, 상기 화학식 2의 화합물은 하기 화학식 4의 화합물과 벤질알콜 화합물을 수소화나트륨를 사용하여 유기용매 또는 유기용매와 물의 혼합용액 하에서 가열 환류반응시킴으로써 제조될 수 있다:Meanwhile, the compound of Formula 2 may be prepared by heating and refluxing a compound of Formula 4 and a benzyl alcohol compound under an organic solvent or a mixed solution of organic solvent and water using sodium hydride:
<화학식 4>≪ Formula 4 >
상기 화학식 4에서,In Chemical Formula 4,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
상기 유기 용매는 N,N-디메틸포름아마이드, 아세토니트릴, 테트라하이드로퓨란을 포함하는 군중에서 선택될 수 있으며, N,N-디메틸포름아마이드가 좀 더 바람직하나 이에 한정되지는 않는다. The organic solvent may be selected from the group comprising N, N-dimethylformamide, acetonitrile, tetrahydrofuran, and N, N-dimethylformamide is more preferred but not limited thereto.
참고로, 하기 반응식 1에는 화합물 3 또는 4로부터 화학식 1의 화합물을 제조하는 예시적인 개략 반응도를 나타내었다. For reference, Scheme 1 below shows an exemplary schematic reaction diagram for preparing the compound of Formula 1 from compound 3 or 4.
<반응식 1><Reaction Scheme 1>
상기 반응식 1에서, In the above Reaction Scheme 1,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
또한, 본 발명은 하기 화학식 5의 화합물과 벤질할라이드 화합물 또는 벤질알콜 화합물을 유기용매 하에서 반응시킴으로써 하기 화학식 1의 화합물을 제조하는 단계를 포함하는 유레아 유도체의 제조방법을 제공한다:In addition, the present invention provides a method for preparing a urea derivative comprising the step of preparing a compound of formula 1 by reacting a compound of formula 5 and a benzyl halide compound or benzyl alcohol compound in an organic solvent:
<화학식 5>≪ Formula 5 >
<화학식 1>≪ Formula 1 >
상기 화학식 1 또는 5에서, In Chemical Formula 1 or 5,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수조가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one tank of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
상기 벤질할라이드 화합물은 벤질할라이드, 니트로벤질할라이드, 할로벤질할라이드, 메틸벤질할라이드, 에틸벤질할라이드, 프로필벤질할라이드, 메톡시벤질할라이드, 디메톡시벤질할라이드로 구성된 군 중에서 선택되는 어느 하나일 수 있으며, 상기 벤질알콜 화합물는 벤질알콜, 니트로벤질 알콜, 할로벤질알콜, 메틸벤질알콜, 에틸벤질알콜, 프로필벤질알콜, 메톡시벤질알콜, 디메톡시벤질알콜로 구성된 군 중에서 선택되는 어느 하나 일 수 있으나 이에 한정되지는 않는다.The benzyl halide compound may be any one selected from the group consisting of benzyl halide, nitrobenzyl halide, halobenzyl halide, methyl benzyl halide, ethyl benzyl halide, propyl benzyl halide, methoxy benzyl halide, dimethoxy benzyl halide, The benzyl alcohol compound may be any one selected from the group consisting of benzyl alcohol, nitrobenzyl alcohol, halobenzyl alcohol, methyl benzyl alcohol, ethyl benzyl alcohol, propyl benzyl alcohol, methoxy benzyl alcohol, dimethoxybenzyl alcohol, but is not limited thereto. Do not.
상기 유기용매는 아세토니트릴, 디메틸포름알데하이드, 디메틸설폭사이드, 테트라하이드로퓨란, 디에틸에테르로 구성된 군 중에서 선택되는 어느 하나 일 수 있으나 이에 한정되지 않으며, The organic solvent may be any one selected from the group consisting of acetonitrile, dimethylformaldehyde, dimethyl sulfoxide, tetrahydrofuran, diethyl ether, but is not limited thereto.
상기 화학식 5의 화합물과 벤질할라이드 화합물의 반응에 사용되는 촉매는 테트라헵틸암모늄 브로마이드(THAB), 테트라부틸암모늄 아이오다이드(TBAI)일 수 있으며, 상기 반응에 사용되는 염기는 탄산칼륨, 탄산나트륨, 트리에틸아민, 디이소프로필에틸아민, 피리딘으로 구성된 군 중에서 선택된 어느 하나 일 수 있으며, 상기 반응은 10 내지 90 ℃ 범위에서 수행될 수 있으나, 20 내지 30 ℃ 범위가 바람직하며, 반응은 3 내지 24시간 동안 이루어질 수 있으나, 8 내지 12시간인 것이 좀더 바람직하고, The catalyst used in the reaction of the compound of Formula 5 and the benzyl halide compound may be tetraheptyl ammonium bromide (THAB), tetrabutylammonium iodide (TBAI), and the base used in the reaction is potassium carbonate, sodium carbonate, tri It may be any one selected from the group consisting of ethylamine, diisopropylethylamine, pyridine, the reaction may be carried out in the range of 10 to 90 ℃, 20 to 30 ℃ range is preferred, the reaction is 3 to 24 hours It can be done for a while, but more preferably 8 to 12 hours,
상기 화학식 5의 화합물과 벤질알콜 화합물의 반응은 디이소프로필아조디카복실레이트, 디에틸아조디카복실레이트, 트리페닐포스핀을 이용한 미츠노부 반응을 사용할 수 있으나 이에 한정되지는 않으며, 상기 반응은 10 내지 40 ℃ 범위에서 수행될 수 있으나, 20 내지 30 ℃ 범위가 바람직하며, 반응은 3 내지 24시간 동안 이루어질 수 있으나, 8 내지 12시간인 것이 좀더 바람직하다. The reaction of the compound of Formula 5 and the benzyl alcohol compound may be a mitsunobu reaction using diisopropyl azodicarboxylate, diethyl azodicarboxylate, triphenylphosphine, but is not limited thereto. Although it may be carried out in the range of 40 to 40 ℃, preferably 20 to 30 ℃ range, the reaction may be made for 3 to 24 hours, more preferably 8 to 12 hours.
또한, 상기 화학식 5의 화합물은 하기 화학식 3의 화합물과 아이소시아네이트 화합물 또는 아이소티오시아네이트 화합물을 유기용매 하에서 반응시켜 제조될 수 있다. In addition, the compound of Formula 5 may be prepared by reacting a compound of Formula 3 with an isocyanate compound or isothiocyanate compound under an organic solvent.
<화학식 3><Formula 3>
상기 화학식 3에서, In Formula 3,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
상기 유기용매는 아세토니트릴, 테트라하이드로퓨란, 1,2-디클로로에탄, 메틸렌클로라이드으로 구성된 군중에서 선택될 수 있으며, 아세토니트릴이 좀더 바람직하나 이에 한정되지는 않으며, 상기 반응은 50 내지 100 ℃ 범위에서 수행될 수 있으며, 반응은 3 내지 24시간 동안 이루어질 수 있으나, 7 내지 10시간인 것이 좀더 바람직하다. The organic solvent may be selected from the group consisting of acetonitrile, tetrahydrofuran, 1,2-dichloroethane, methylene chloride, acetonitrile is more preferred, but is not limited thereto, the reaction is in the range of 50 to 100 ℃ The reaction may be carried out for 3 to 24 hours, more preferably 7 to 10 hours.
또한, 상기 화학식 5의 화합물은 상기 화학식 6의 화합물을 수소 1기압 하에서, Pd(OH)2를 사용하여 탈벤질화시켜 제조될 수 있다:In addition, the compound of Formula 5 may be prepared by debenzylating the compound of Formula 6 using Pd (OH) 2 under 1 atmosphere of hydrogen:
<화학식 6>(6)
상기 화학식 6에서, In Formula 6,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
상기 반응은 10 내지 40 ℃ 범위에서 수행될 수 있으나, 20 내지 30 ℃ 범위가 바람직하며, 반응은 3 내지 24시간 동안 이루어질 수 있으나, 4 내지 8시간인 것이 좀더 바람직하다. The reaction may be carried out in the range of 10 to 40 ℃, preferably 20 to 30 ℃ range, the reaction may be made for 3 to 24 hours, more preferably 4 to 8 hours.
또한, 상기 화학식 6의 화합물은 하기 화학식 7의 화합물과 아이소시아네이트 화합물 또는 아이소티오시아네이트 화합물을 반응시켜 제조될 수 있다:In addition, the compound of Formula 6 may be prepared by reacting a compound of Formula 7 with an isocyanate compound or isothiocyanate compound:
<화학식 7>≪ Formula 7 >
상기 화학식 7에서, In Formula 7,
X는 탄소 또는 질소이다.X is carbon or nitrogen.
참고로, 하기 반응식 2 에는 화학식 3 또는 7의 화합물로부터 화학식 1의 화합물을 제조하는 예시적인 개략 반응도를 나타내었다.For reference, Scheme 2 below shows an exemplary schematic reaction diagram for preparing the compound of Formula 1 from the compound of Formula 3 or 7.
<반응식 2><Reaction Scheme 2>
상기 반응식 2에서, In the above Reaction Scheme 2,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X는 탄소 또는 질소이며, X is carbon or nitrogen,
Y는 산소 또는 황이며, Y is oxygen or sulfur,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
본 발명은 상기 세 번째 기술적 과제를 달성하기 위하여, The present invention to achieve the third technical problem,
상기 화학식 1로 표시되는 유레아 유도체 또는 이의 약제학적 허용 가능한 염을 유효성분으로 포함하는 약학조성물을 제공한다.It provides a pharmaceutical composition comprising the urea derivative represented by the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 약학조성물은 상기 화학식 1로 표시되는 유레아 화합물 또는 이의 약제학적 허용 가능한 염에 담체, 보조제 또는 희석제 등을 포함시켜 제제화 방법으로 제형화하여 경구투여 또는 비경구투여에 적합한 형태로 제조될 수 있다. 경구투여용은 정제, 캡슐제, 용액, 시럽제, 현탁제 등의 형태로 제조될 수 있으며, 비경구투여용은 복강, 피하, 근육, 경피에 대한 주사제 형태로 제조될 수 있다.The pharmaceutical composition of the present invention may be prepared in a form suitable for oral administration or parenteral administration by including a carrier, adjuvant or diluent, etc. in the urea compound represented by Formula 1 or a pharmaceutically acceptable salt thereof. have. Oral administration may be prepared in the form of tablets, capsules, solutions, syrups, suspensions and the like, parenteral administration may be prepared in the form of injections for the abdominal cavity, subcutaneous, muscle, transdermal.
본 발명의 약학조성물은 mPTP의 작용을 선택적으로 억제하여 미토콘드리아의 기능을 향상시키는 신경보호제로써 1일 유효투여량은 성인을 기준으로 0.01 내지 1000 mg/day이나, 투여용량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태 또는 질환 정도에 따라 달라질 수 있으며, 의사 또는 약사의 판단에 따라 일정 시간간격으로 1일 1회 내지 수회로 분할 투여할 수 있다.The pharmaceutical composition of the present invention is a neuroprotective agent that selectively inhibits the action of mPTP and improves the function of mitochondria. The effective daily dose is 0.01 to 1000 mg / day based on an adult, but the dosage is the age, weight, It may vary depending on sex, dosage form, health condition or degree of disease, and may be divided once or several times a day at regular intervals according to the judgment of a doctor or pharmacist.
본 발명의 약학 조성물은 뇌신경질환 예방 또는 치료용으로 사용될 수 있으며, 상기 뇌신경질환은 알츠하이머병, 파킨슨병 헌팅톤병, 허혈성질환, 당뇨병, 정신분열증으로 이루어진 군에서 선택되는 어느 하나 이상일 수 있다.The pharmaceutical composition of the present invention can be used for the prevention or treatment of cerebral nerve disease, the brain neurological disease may be any one or more selected from the group consisting of Alzheimer's disease, Parkinson's Huntington's disease, ischemic disease, diabetes, schizophrenia.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 들어 본 발명을 더욱 상세하게 설명한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 이에 의해 본 발명의 내용이 한정되는 것은 아니다.
BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to preferred embodiments for better understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited thereto.
실시예Example . . 유레아Urea 유도체의 합성 Synthesis of derivatives
실시예Example 1.1. 3-(3- 1.1. 3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-아민) Pyridin-2-amine
플라스크에 수산화나트륨 (6g, 0.150 mol)을 물 (10 mL)와 메틸렌클로라이드 (15 mL)에 녹인 후, 2-아미노-3-히드록시 피리딘을 조금씩 적가한 뒤 교반 시키고, 테트라브로모암모늄브로마이드 (156 mg, 0.48 mmol)을 추가하여 15분 동안 상온에서 교반 시킨다. 교반 시키고 있는 반응물에 메틸렌클로라이드 (10 mL)에 녹인 3-플루오르 벤질 브로마이드 용액을 상온에서 천천히 적가한 뒤, 상온에서 20 시간 동안 교반한다. 반응 종결 후, 유기층과 물층을 분리한 뒤, 물 층을 메틸렌클로라이드으로 추출하여 준다. 유기층을 모두 합쳐서 황산나트륨으로 건조 후 감압 여과하여 감압 농축한다. 잔여물을 컬럼크로마토그래피법 (초산에틸/노르말헥산 =1/2)으로 분리 정제하여 목적화합물을 70.1 %의 수율로 2.46 g 얻었다. In a flask, sodium hydroxide (6 g, 0.150 mol) was dissolved in water (10 mL) and methylene chloride (15 mL), and 2-amino-3-hydroxy pyridine was added dropwise and stirred, followed by tetrabromoammonium bromide ( 156 mg, 0.48 mmol) is added and stirred at room temperature for 15 minutes. 3-fluoro benzyl bromide solution dissolved in methylene chloride (10 mL) was slowly added dropwise to the reactant at room temperature, followed by stirring at room temperature for 20 hours. After completion of the reaction, the organic layer and the water layer were separated, and then the water layer was extracted with methylene chloride. The organic layers were combined, dried over sodium sulfate, filtered under reduced pressure and concentrated under reduced pressure. The residue was separated and purified by column chromatography (ethyl acetate / normal hexane = 1/2) to obtain 2.46 g of the title compound in a yield of 70.1%.
1H NMR (400 MHz, CDCl3) δ = 4.68 (2H, brs, NH2), 5.06 (2H, s, OCH2Ph), 6.59 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 6.93 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.02-7.05 (1H, m, Ph), 7.13 (1H, dd, J1 = 9.2 Hz, J2 = 2.0 Hz, Ph), 7.18 (1H, d, J = 8.4 Hz, Ph), 7.33-7.39 (1H, m, Ph), 7.69 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.68 (2H, brs, NH 2 ), 5.06 (2H, s, OCH 2 Ph), 6.59 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 6.93 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.02-7.05 (1H, m, Ph), 7.13 (1H, dd, J 1 = 9.2 Hz, J 2 = 2.0 Hz, Ph), 7.18 (1H, d, J = 8.4 Hz, Ph), 7.33-7.39 (1H, m, Ph), 7.69 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py )
실시예Example 1.2. 1-(3-(3- 1.2. 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유U 레아ostrich
3-(3-플루오르벤질옥시)피리딘-2-아민 (150 mg, 0.69 mmol)과 2-플루오르 아이소시아네이트 (930 μL, 0.82 mmol)를 테트라하이드로퓨란(0.25 M)에 녹인 후 5시간 동안 가열 환류시킨다. 반응 종결 후, 용매를 감압 농축하고, 잔여물을 디에틸에테르로 씻어준 뒤, 감압 여과하여 71.65%의 수율로 목적화합물 175 mg을 얻었다. 3- (3-fluorobenzyloxy) pyridin-2-amine (150 mg, 0.69 mmol) and 2-fluoro isocyanate (930 μL, 0.82 mmol) were dissolved in tetrahydrofuran (0.25 M) and heated to reflux for 5 hours. Let's do it. After completion of the reaction, the solvent was concentrated under reduced pressure, the residue was washed with diethyl ether and filtered under reduced pressure to obtain 175 mg of the target compound in a yield of 71.65%.
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.88 (1H, dd, J1 = 5.09 Hz, J2 = 8.02 Hz, Py), 7.00-7.02 (1H, m, Ph), 7.06-7.11 (5H, m, Py+Ph), 7.14 (1H, d, J = 7.92 Hz, Ph), 7.54 (1H, s, NH), 7.90 (1H, dd, J1 = 1.24 Hz, J2 = 5.09 Hz, Py), 8.30-8.35 (1H, m, Ph), 12.20 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.88 (1H, dd, J 1 = 5.09 Hz, J2 = 8.02 Hz, Py), 7.00-7.02 (1H, m, Ph), 7.06-7.11 (5H, m, Py + Ph), 7.14 (1H, d, J = 7.92 Hz, Ph), 7.54 (1H, s, NH), 7.90 (1H, dd, J 1 = 1.24 Hz , J2 = 5.09 Hz, Py), 8.30-8.35 (1H, m, Ph), 12.20 (1H, s, NH)
이하, 하기 화합물 1 내지 47을 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
Hereinafter, Compounds 1 to 47 were obtained by the same method as the Examples, and the analysis results of these compounds were as follows:
화합물 1: 1-(3-(Compound 1: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.88 (1H, dd, J1 = 5.09 Hz, J2 = 8.02 Hz, Py), 6.99-7.01 (1H, m, Ph), 7.07-7.16 (2H, m, Py+Ph), 7.38-7.43 (5H, m, Ph), 7.56 (1H, s, NH), 7.88 (1H, dd, J1 = 1.19 Hz, J2 = 5.09 Hz, Py), 8.30-8.35 (1H, m, Ph), 12.22 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.88 (1H, dd, J 1 = 5.09 Hz, J 2 = 8.02 Hz, Py), 6.99-7.01 (1H, m, Ph), 7.07-7.16 (2H, m, Py + Ph), 7.38-7.43 (5H, m, Ph), 7.56 (1H, s, NH), 7.88 (1H, dd, J 1 = 1.19 Hz, J 2 = 5.09 Hz, Py), 8.30-8.35 (1H, m, Ph), 12.22 (1H, s, NH)
화합물 2: 1-(3-(Compound 2: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.74-6.77 (1H, m, Ph), 6.89 (1H, dd, J1 = 5.10 Hz, J2 = 8.02 Hz, Py), 7.15 (1H, dd, J1 = 1.12 Hz, J2 = 8.02 Hz, Py), 7.38-7.43 (5H, m, Ph), 7.27 (1H, s, NH), 7.5-7.55 (2H, m, Ph), 7.86 (1H, dd, J1 = 1.12 Hz, J2 = 5.10 Hz, Py), 12.0 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.74-6.77 (1H, m, Ph), 6.89 (1H, dd, J 1 = 5.10 Hz, J 2 = 8.02 Hz, Py), 7.15 (1H, dd, J 1 = 1.12 Hz, J 2 = 8.02 Hz, Py), 7.38-7.43 (5H, m, Ph), 7.27 (1H, s, NH), 7.5-7.55 ( 2H, m, Ph), 7.86 (1H, dd, J 1 = 1.12 Hz, J 2 = 5.10 Hz, Py), 12.0 (1H, s, NH)
화합물 3: 1-(3-(Compound 3: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(3,4-Pyridin-2-yl) -3- (3,4- 다이클로로페닐Dichlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.91 (1H, dd, J1 = 5.13 Hz, J2 = 8.03 Hz, Py), 7.17 (1H, dd, J1 = 1.23 Hz, J2 = 8.03 Hz, Py), 7.36 (1H, d, J = 8.76 Hz, Ph), 7.38-7.42 (5H, m, Ph), 7.47 (1H, dd, J1 = 2.45 Hz, J2 = 8.76 Hz, Ph), 7.54 (1H, s, NH), 7.80 (1H, d, J = 2.45 Hz, Ph), 7.86 (1H, dd, J1 = 1.23 Hz, J2 = 5.13 Hz, Py), 12.04 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.91 (1H, dd, J 1 = 5.13 Hz, J 2 = 8.03 Hz, Py), 7.17 (1H, dd, J 1 = 1.23 Hz, J 2 = 8.03 Hz, Py), 7.36 (1H, d, J = 8.76 Hz, Ph), 7.38-7.42 (5H, m, Ph), 7.47 (1H, dd, J 1 = 2.45 Hz, J 2 = 8.76 Hz, Ph), 7.54 (1H, s, NH), 7.80 (1H, d, J = 2.45 Hz, Ph), 7.86 (1H, dd, J 1 = 1.23 Hz, J 2 = 5.13 Hz, Py), 12.04 (1H, s, NH)
화합물 4: 1-(3-(Compound 4: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-벤질 ) Pyridin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 4.62 (2H, d, J = 5.76 Hz, OCH2Ph), 5.10 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.12 Hz, J2 = 7.99 Hz, Py), 7.09 (1H, dd, J1 = 1.33 Hz, J2 = 7.99 Hz, Py), 7.23-7.41 (10H, m, 2Ph), 7.48 (1H, s, NH), 7.72( 1H, dd, J1 = 1.33 Hz, J2 = 5.12 Hz, Py), 9.22 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.62 (2H, d, J = 5.76 Hz, OCH 2 Ph), 5.10 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.12 Hz , J 2 = 7.99 Hz, Py), 7.09 (1H, dd, J 1 = 1.33 Hz, J 2 = 7.99 Hz, Py), 7.23-7.41 (10H, m, 2Ph), 7.48 (1H, s, NH) , 7.72 (1H, dd, J 1 = 1.33 Hz, J 2 = 5.12 Hz, Py), 9.22 (1H, s, NH)
화합물 5: 1-(3-(Compound 5: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.87 (1H, dd, J1 = 5.10 Hz, J2 = 8.01 Hz, Py), 7.05-7.09 (1H, m, Ph), 7.14 (1H, dd, J1 = 1.27 Hz, J2 = 8.01 Hz, Py), 7.23-7.36 (2H, m, Ph), 7.38-7.42 (5H, m, Ph), 7.51 (1H, brs, NH), 7.59-7.62 (2H, m, Ph), 7.85 (1H, dd, J1 = 1.27 Hz, J2 = 5.10 Hz, Py), 11.85 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.87 (1H, dd, J 1 = 5.10 Hz, J 2 = 8.01 Hz, Py), 7.05-7.09 (1H, m, Ph), 7.14 (1H, dd, J 1 = 1.27 Hz, J 2 = 8.01 Hz, Py), 7.23-7.36 (2H, m, Ph), 7.38-7.42 (5H, m, Ph), 7.51 ( 1H, brs, NH), 7.59-7.62 (2H, m, Ph), 7.85 (1H, dd, J 1 = 1.27 Hz, J 2 = 5.10 Hz, Py), 11.85 (1H, s, NH)
화합물 6: 1-(3-(Compound 6: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.13 (2H, s, OCH2Ph), 6.86 (1H, dd, J1 = 5.09 Hz, J2 = 7.98 Hz, Py), 7.12-7.14 (3H, m, Ph+Py), 7.37-7.42 (5H, m, Ph), 7.47-7.50 (3H, m, Ph+NH), 7.84 (1H, dd, J1 = 1.26 Hz, J2 = 5.07 Hz, Py), 11.73 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.13 (2H, s, OCH 2 Ph), 6.86 (1H, dd, J 1 = 5.09 Hz, J 2 = 7.98 Hz , Py), 7.12-7.14 (3H, m, Ph + Py), 7.37-7.42 (5H, m, Ph), 7.47-7.50 (3H, m, Ph + NH), 7.84 (1H, dd, J 1 = 1.26 Hz, J 2 = 5.07 Hz, Py), 11.73 (1H, s, NH)
화합물 7: 1-(3-(Compound 7: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.28 (2H, s, OCH2Ph), 7.08 (1H, dd, J1 = 5.05 Hz, J2 = 8.06 Hz, Py), 7.33-7.41 (3H, m, Ph+Py), 7.48 (2H, t, J = 7.89 Hz, Ph), 7.54-7.57 (4H, m, Ph), 7.63-7.67 (2H, m, Ph), 7.94 (1H, d, J = 7.74 Hz, Ph), 8.04 (1H, dd, J1 = 1.17 Hz, J2 = 5.05 Hz, Py), 8.14 (1H, d, J = 8.32 Hz, Ph), 8.18 (1H, d, J = 6.94 Hz, Ph), 8.34 (1H, s, NH), 12.40 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.28 (2H, s, OCH 2 Ph), 7.08 (1H, dd, J 1 = 5.05 Hz, J 2 = 8.06 Hz, Py), 7.33-7.41 ( 3H, m, Ph + Py), 7.48 (2H, t, J = 7.89 Hz, Ph), 7.54-7.57 (4H, m, Ph), 7.63-7.67 (2H, m, Ph), 7.94 (1H, d , J = 7.74 Hz, Ph), 8.04 (1H, dd, J 1 = 1.17 Hz, J 2 = 5.05 Hz, Py), 8.14 (1H, d, J = 8.32 Hz, Ph), 8.18 (1H, d, J = 6.94 Hz, Ph), 8.34 (1H, s, NH), 12.40 (1H, s, NH)
화합물 8: 1-(3-(Compound 8: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(4-(Pyridin-2-yl) -3- (4- ( 트리플루오르메틸Trifluoromethyl )) 페닐Phenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.46 (2H, s, OCH2Ph), 7.39-7.47 (5H, m, Ph), 7.50 (1H, s, NH), 7.52 (1H, m, Py), 7.58 (2H, d, J = 8.0 Hz, Ph), 7.71 (2H, d, J = 8.0 Hz, Ph), 7.77 (2H, dd, J1 = 3.2 Hz, J2 = 8.04 Hz, Py), 11.55 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.46 (2H, s, OCH 2 Ph), 7.39-7.47 (5H, m, Ph), 7.50 (1H, s, NH), 7.52 (1H, m, Py ), 7.58 (2H, d, J = 8.0 Hz, Ph), 7.71 (2H, d, J = 8.0 Hz, Ph), 7.77 (2H, dd, J 1 = 3.2 Hz, J 2 = 8.04 Hz, Py) , 11.55 (1H, s, NH)
화합물 9: 1-(3-(3-Compound 9: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.88 (1H, dd, J1 = 5.09 Hz, J2 = 8.02 Hz, Py), 7.00-7.02 (1H, m, Ph), 7.06-7.11 (5H, m, Py+Ph), 7.14 (1H, d, J = 7.92 Hz, Ph), 7.54 (1H, s, NH), 7.90 (1H, dd, J1 = 1.24 Hz, J2 = 5.09 Hz, Py), 8.30-8.35 (1H, m, Ph), 12.20 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.88 (1H, dd, J 1 = 5.09 Hz, J 2 = 8.02 Hz, Py), 7.00-7.02 (1H, m, Ph), 7.06-7.11 (5H, m, Py + Ph), 7.14 (1H, d, J = 7.92 Hz, Ph), 7.54 (1H, s, NH), 7.90 (1H, dd, J 1 = 1.24 Hz, J 2 = 5.09 Hz, Py), 8.30-8.35 (1H, m, Ph), 12.20 (1H, s, NH)
화합물 10: 1-(3-(3-Compound 10: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.74-6.77 (1H, m, Ph), 6.89 (1H, dd, J1 = 5.10 Hz, J2 = 8.04 Hz, Py), 7.06-7.13 (3H, m, Py+Ph), 7.18 (1H, d, J = 7.74 Hz, Ph), 7.27-7.28 (2H, m, Ph), 7.37-7.41 (1H, m, Ph), 7.51 (1H, m, NH), 7.52-7.56 (1H, m, Ph), 7.87 (1H, dd, J1 = 1.22 Hz, J2 = 5.10 Hz, Py), 11.98 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.74-6.77 (1H, m, Ph), 6.89 (1H, dd, J 1 = 5.10 Hz, J 2 = 8.04 Hz, Py), 7.06-7.13 (3H, m, Py + Ph), 7.18 (1H, d, J = 7.74 Hz, Ph), 7.27-7.28 (2H, m, Ph), 7.37-7.41 (1H, m , Ph), 7.51 (1H, m, NH), 7.52-7.56 (1H, m, Ph), 7.87 (1H, dd, J 1 = 1.22 Hz, J 2 = 5.10 Hz, Py), 11.98 (1H, s , NH)
화합물 11: 1-(3-(3-Compound 11: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(3,4-Pyridin-2-yl) -3- (3,4- 다이클로로페닐Dichlorophenyl ) 유레아) Urea
1H NMR (400 MHz, CDCl3) δ = 5.13 (2H, s, OCH2Ph), 6.91 (1H, dd, J1 = 5.13 Hz, J2 = 8.02 Hz, Py), 7.08-7.11 (2H, m, Ph), 7.13 (1H, dd, J1 = 1.22 Hz, J2 = 5.10 Hz, Py), 7.18 (1H, d, J = 7.82 Hz, Ph), 7.36-7.40 (2H, m, Ph), 7.47 (1H, dd, J1 = 2.47 Hz, J2 = 8.75 Hz, Ph), 7.52 (1H, s, NH), 7.80 (1H, d, J = 2.47 Hz, Ph), 7.87 (1H, dd, J1 = 1.26 Hz, J2 = 5.13 Hz, Py), 12.01 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.13 (2H, s, OCH 2 Ph), 6.91 (1H, dd, J 1 = 5.13 Hz, J 2 = 8.02 Hz, Py), 7.08-7.11 (2H, m, Ph), 7.13 (1H, dd, J 1 = 1.22 Hz, J 2 = 5.10 Hz, Py), 7.18 (1H, d, J = 7.82 Hz, Ph), 7.36-7.40 (2H, m, Ph) , 7.47 (1H, dd, J 1 = 2.47 Hz, J 2 = 8.75 Hz, Ph), 7.52 (1H, s, NH), 7.80 (1H, d, J = 2.47 Hz, Ph), 7.87 (1H, dd , J 1 = 1.26 Hz, J 2 = 5.13 Hz, Py), 12.01 (1H, s, NH)
화합물 12: 1-(3-(3-Compound 12: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-벤질 ) Pyridin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 4.62 (2H, d, J = 5.84 Hz, OCH2Ph), 5.09 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.10 Hz, J2 = 8.0 Hz, Py), 7.05 (1H, dd, J1 = 1.30 Hz, J2 = 8.0 Hz, Py), 7.07-7.10 (2H, m, Ph), 7.17 (1H, s, NH), 7.31-7.39 (5H, m, Ph), 7.45 (1H, s, NH), 7.74 (1H, dd, J1 = 1.30 Hz, J2 = 5.10 Hz, Py), 9.90 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.62 (2H, d, J = 5.84 Hz, OCH 2 Ph), 5.09 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.10 Hz , J 2 = 8.0 Hz, Py), 7.05 (1H, dd, J 1 = 1.30 Hz, J2 = 8.0 Hz, Py), 7.07-7.10 (2H, m, Ph), 7.17 (1H, s, NH), 7.31-7.39 (5H, m, Ph), 7.45 (1H, s, NH), 7.74 (1H, dd, J 1 = 1.30 Hz, J 2 = 5.10 Hz, Py), 9.90 (1H, s, NH)
화합물 13: 1-(3-(3-Compound 13: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.12 (2H, s, OCH2Ph), 6.87 (1H, dd, J1 = 5.08 Hz, J2 = 8.0 Hz, Py), 7.06-7.12 (4H, m, Ph+Py), 7.19 (1H, d, J = 7.65 Hz, Py), 7.32-7.42 (3H, m, Ph), 7.49 (1H, brs, NH), 7.61 (2H, d, J = 7.53 Hz, Ph), 7.86 (1H, dd, J1 = 1.2 Hz, J2 = 5.08 Hz, Py), 11.82 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.12 (2H, s, OCH 2 Ph), 6.87 (1H, dd, J 1 = 5.08 Hz, J 2 = 8.0 Hz, Py), 7.06-7.12 (4H, m, Ph + Py), 7.19 (1H, d, J = 7.65 Hz, Py), 7.32-7.42 (3H, m, Ph), 7.49 (1H, brs, NH), 7.61 (2H, d, J = 7.53 Hz, Ph), 7.86 (1H, dd, J 1 = 1.2 Hz, J 2 = 5.08 Hz, Py), 11.82 (1H, s, NH)
화합물 14: 1-(3-(3-Compound 14: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.12 (2H, s, OCH2Ph), 6.86 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.08-7.09 (3H, m, Ph+Py), 7.12 (2H, m, Ph), 7.18 (1H, m, Ph), 7.37-7.39 (1H, m, Ph), 7.48 (3H, m, Ph+NH), 7.86 (1H, dd, J1 = 1.28 Hz, J2 = 5.12 Hz, Py), 11.71 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.12 (2H, s, OCH 2 Ph), 6.86 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz , Py), 7.08-7.09 (3H, m, Ph + Py), 7.12 (2H, m, Ph), 7.18 (1H, m, Ph), 7.37-7.39 (1H, m, Ph), 7.48 (3H, m, Ph + NH), 7.86 (1H, dd, J 1 = 1.28 Hz, J 2 = 5.12 Hz, Py), 11.71 (1H, s, NH)
화합물 15: 1-(3-(3-Compound 15: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.32 (2H, s, OCH2Ph), 7.11 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.16-7.21 (1H, m, Ph), 7.41 (1H, d, J = 8.0 Hz, Ph), 7.45 (1H, dd, J1 = 6.0 Hz, J2= 8.0 Hz, Ph), 7.47-7.60 (4H, m, Ph), 7.69 (2H, d, J = 8.4 Hz, Ph), 7.97 (1H, d, J = 8.0 Hz, Ph), 8.06 (1H, d, J = 4.8 Hz, Py), 8.17 (1H, d, J = 8.4 Hz, Ph), 8.22 (1H, d, J = 7.6 Hz, Ph), 8.58 (1H, s, NH), 12.45 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.32 (2H, s, OCH 2 Ph), 7.11 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.16-7.21 ( 1H, m, Ph), 7.41 (1H, d, J = 8.0 Hz, Ph), 7.45 (1H, dd, J 1 = 6.0 Hz, J 2 = 8.0 Hz, Ph), 7.47-7.60 (4H, m, Ph), 7.69 (2H, d, J = 8.4 Hz, Ph), 7.97 (1H, d, J = 8.0 Hz, Ph), 8.06 (1H, d, J = 4.8 Hz, Py), 8.17 (1H, d , J = 8.4 Hz, Ph), 8.22 (1H, d, J = 7.6 Hz, Ph), 8.58 (1H, s, NH), 12.45 (1H, s, NH)
화합물 16: 1-(3-(3-Compound 16: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(4-(Pyridin-2-yl) -3- (4- ( 트리플루오르메Trifluoromethane 틸)Yl) 페닐Phenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.29 (2H, s, OCH2Ph), 6.92 (1H, dd, J1 = 5.5 Hz, J2 = 8.0 Hz, Py), 7.06-7.15 (3H, m, Ph+Py), 7.19 (1H, d, J = 7.6 Hz, Ph), 7.37-7.42 (1H, m, Ph), 7.55 (1H, s, NH), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 7.89 (1H, dd, J1 = 1.2 Hz, J2 = 5.2 Hz, Py), 12.13 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.29 (2H, s, OCH 2 Ph), 6.92 (1H, dd, J 1 = 5.5 Hz, J 2 = 8.0 Hz, Py), 7.06-7.15 (3H, m, Ph + Py), 7.19 (1H, d, J = 7.6 Hz, Ph), 7.37-7.42 (1H, m, Ph), 7.55 (1H, s, NH), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 7.89 (1H, dd, J 1 = 1.2 Hz, J2 = 5. 2 Hz, Py), 12.13 (1H, s, NH)
화합물 17: 1-(3-(4-Compound 17: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.09 (2H, s, OCH2Ph), 6.90 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.00-7.03 (1H, m, Ph), 7.07-7.16 (5H, m, Ph+ Py), 7.37-7.41 (2H, m, Ph), 7.52 (1H, s, NH), 7.90 (1H, dd, J1 = 4.8 Hz, J2 = 1.2 Hz, Py), 8.30-8.34 (1H, m, Ph), 12.20 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.09 (2H, s, OCH 2 Ph), 6.90 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.00-7.03 (1H, m, Ph), 7.07-7.16 (5H, m, Ph + Py), 7.37-7.41 (2H, m, Ph), 7.52 (1H, s, NH), 7.90 (1H, dd, J 1 = 4.8 Hz, J 2 = 1.2 Hz, Py), 8.30-8.34 (1H, m, Ph), 12.20 (1H, s, NH)
화합물 18: 1-(3-(4-Compound 18: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.09 (2H, s, OCH2Ph), 6.74-6.78 (1H, m, Ph), 6.89 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.09-7.16 (3H, m, Ph+Py), 7.25-7.27 (2H, m, Ph), 7.37-7.40 (2H, m, Ph), 7.49 (1H, s, NH), 7.51-7.55 (1H, m, Ph), 7.86 (1H, J1 = 5.2 Hz, J2 = 1.6 Hz, Py), 11.98 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.09 (2H, s, OCH 2 Ph), 6.74-6.78 (1H, m, Ph), 6.89 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.09-7.16 (3H, m, Ph + Py), 7.25-7.27 (2H, m, Ph), 7.37-7.40 (2H, m, Ph), 7.49 (1H, s, NH), 7.51 -7.55 (1H, m, Ph), 7.86 (1H, J 1 = 5.2 Hz, J 2 = 1.6 Hz, Py), 11.98 (1H, s, NH)
화합물 19: 1-(3-(4-Compound 19: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(3,4-Pyridin-2-yl) -3- (3,4- 다이클로로페닐Dichlorophenyl ) 유레아) Urea
1H NMR (400 MHz, CDCl3) δ = 5.09 (2H, s, OCH2Ph), 6.92 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.09-7.17 (3H, m, Ph+Py), 7.32-7.40 (4H, m, Ph), 7.47 (1H, dd, J1 = 8.8 Hz, J2 = 2.4 Hz, Ph), 7.79 (1H, d, J = 2.4 Hz, Ph), 7.87 (1H, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 12.01 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.09 (2H, s, OCH 2 Ph), 6.92 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.09-7.17 (3H, m, Ph + Py), 7.32-7.40 (4H, m, Ph), 7.47 (1H, dd, J 1 = 8.8 Hz, J2 = 2.4 Hz, Ph), 7.79 (1H, d, J = 2.4 Hz, Ph ), 7.87 (1H, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 12.01 (1H, s, NH)
화합물 20: 1-(3-(4-Compound 20: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.09 (2H, s, OCH2Ph), 6.90 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.04 (1H, d, J = 8.0 Hz, Py). 7.09-7.16 (3H, m, Ph), 7.22-7.26 (1H, m, Ph), 7.37-7.40 (2H, m, Ph), 7.48-7.50 (2H, m, Ph), 7.67 (1H, s, NH), 7.87 (1H, d, J = 4.8 Hz, Py), 11.96 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.09 (2H, s, OCH 2 Ph), 6.90 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.04 (1H, d, J = 8.0 Hz, Py). 7.09-7.16 (3H, m, Ph), 7.22-7.26 (1H, m, Ph), 7.37-7.40 (2H, m, Ph), 7.48-7.50 (2H, m, Ph), 7.67 (1H, s, NH), 7.87 (1H, d, J = 4.8 Hz, Py), 11.96 (1H, s, NH)
화합물 21: 1-(3-(4-Compound 21: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(4-(Pyridin-2-yl) -3- (4- ( 트리플루오르메Trifluoromethane 틸)Yl) 페닐Phenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.10 (2H, s, OCH2Ph), 6.90 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.12 (2H, t, J = 8.8 Hz, Ph), 7.17 (1H, dd, J1 = 8.0 Hz, J2 = 1.6 Hz, Py), 7.37-7.41 (2H, m, Ph), 7.53 (1H, s, NH), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 7.88 (1H, J1 = 5.2 Hz, J2 = 1.6 Hz, Py), 12.13 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.10 (2H, s, OCH 2 Ph), 6.90 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.12 (2H, t, J = 8.8 Hz, Ph), 7.17 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.6 Hz, Py), 7.37-7.41 (2H, m, Ph), 7.53 (1H, s, NH), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 7.88 (1H, J 1 = 5.2 Hz, J 2 = 1.6 Hz, Py), 12.13 (1H, s, NH)
화합물 22: 1-(3-(4-Compound 22: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.12 (2H, s, OCH2Ph), 6.93 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.13 (2H, t, J = 8.4 Hz, Ph), 7.16 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.39-7.43 (2H, m, Ph), 7.49-7.56 (3H, m, Ph), 7.63 (1H, brs, Ph), 7.65 (1H, s, NH), 7.87 (1H, d, J = 8.0 Hz, Ph), 7.98 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.22 (2H, d, J = 7.2 Hz, Ph), 12.40 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.12 (2H, s, OCH 2 Ph), 6.93 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.13 (2H, t, J = 8.4 Hz, Ph), 7.16 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.39-7.43 (2H, m, Ph), 7.49-7.56 (3H, m, Ph) , 7.63 (1H, brs, Ph), 7.65 (1H, s, NH), 7.87 (1H, d, J = 8.0 Hz, Ph), 7.98 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz , Py), 8.22 (2H, d, J = 7.2 Hz, Ph), 12.40 (1H, s, NH)
화합물 23: 1-(3-(2-Compound 23: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.32 (2H, s, OCH2Ph), 7.08 (2H, m, Ph+Py), 7.18 (1H, t, J = 8.0 Hz, Ph), 7.26-7.31 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Ph), 7.41-7.43 (2H, m, Ph), 7.53-7.55 (1H, m, Ph), 7.57 (1H, d, J = 8.0 Hz, Py), 7.69-7.71 (1H, m, Ph), 7.92 (1H, d, J = 8.0 Hz, Py), 8.20-8.24 (td, J1 = 2.0 Hz, J2 = 8.0 Hz, Ph), 8.31 (1H, s, NH), 12.01 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.32 (2H, s, OCH 2 Ph), 7.08 (2H, m, Ph + Py), 7.18 (1H, t, J = 8.0 Hz, Ph), 7.26-7.31 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Ph), 7.41-7.43 (2H, m, Ph), 7.53-7.55 (1H, m, Ph), 7.57 (1H, d , J = 8.0 Hz, Py), 7.69-7.71 (1H, m, Ph), 7.92 (1H, d, J = 8.0 Hz, Py), 8.20-8.24 (td, J 1 = 2.0 Hz, J 2 = 8.0 Hz, Ph), 8.31 (1H, s, NH), 12.01 (1H, s, NH)
화합물 24: 1-(3-(2-Compound 24: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.24 (2H, s, OCH2Ph), 6.91-6.94 (1H, m, Ph), 7.18 (1H, d, J = 8.4 Hz, Py), 7.30-7.38 (3H, m, Ph), 7.46-7.48 (3H, m, Ph+Py), 7.54 (1H, brs, NH), 7.80 (1H, s, Ph), 7.88 (1H, d, J = 4.8 Hz, Py), 12.01 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.24 (2H, s, OCH 2 Ph), 6.91-6.94 (1H, m, Ph), 7.18 (1H, d, J = 8.4 Hz, Py), 7.30- 7.38 (3H, m, Ph), 7.46-7.48 (3H, m, Ph + Py), 7.54 (1H, brs, NH), 7.80 (1H, s, Ph), 7.88 (1H, d, J = 4.8 Hz , Py), 12.01 (1H, s, NH)
화합물 25: 1-(3-(2-Compound 25: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3,4-Pyridin-2-yl) -3- (3,4- 다이클로로페닐Dichlorophenyl ) 유레아) Urea
1H NMR (400 MHz, CDCl3) δ = 5.24 (2H, s, OCH2Ph), 6.74-6.78 (1H, m, Ph), 6.91 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.17 (1H, d, J = 7.6 Hz, Py), 7.27-7.35 (2H, m, Ph), 7.43-7.46 (2H, m, Ph), 7.52-7.55 (2H, m, Ph+NH), 7.88 (1H, d, J = 8.0 Hz, Ph), 11.98 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.24 (2H, s, OCH 2 Ph), 6.74-6.78 (1H, m, Ph), 6.91 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.17 (1H, d, J = 7.6 Hz, Py), 7.27-7.35 (2H, m, Ph), 7.43-7.46 (2H, m, Ph), 7.52-7.55 (2H, m, Ph + NH), 7.88 (1H, d, J = 8.0 Hz, Ph), 11.98 (1H, s, NH)
화합물 26: 1-(3-(2-Compound 26: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-벤질 ) Pyridin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 4.62 (2H, d, J = 6.0 Hz, OCH2Ph), 5.21 (2H, s, OCH2Ph), 6.82 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.10 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Ph), 7.26-7.34 (4H, m, Ph), 7.35-7.40 (3H, m, Ph), 7.42-7.45 (2H, m, Ph) 7.48 (1H, s, NH), 7.74 (1H, dd, J1 = 1.2 Hz, J2 = 5.2 Hz, Py), 9.91 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.62 (2H, d, J = 6.0 Hz, OCH 2 Ph), 5.21 (2H, s, OCH 2 Ph), 6.82 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.10 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Ph), 7.26-7.34 (4H, m, Ph), 7.35-7.40 (3H, m, Ph) , 7.42-7.45 (2H, m, Ph) 7.48 (1H, s, NH), 7.74 (1H, dd, J 1 = 1.2 Hz, J 2 = 5.2 Hz, Py), 9.91 (1H, s, NH)
화합물 27: 1-(3-(2-Compound 27: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 5.31 (2H, s, OCH2Ph), 7.02-7.09 (2H, m, Py+Ph), 7.32 (2H, t, J = 7.5 Hz, Ph), 7.38-7.43 (2H, m, Ph), 7.53-7.9 (4H, m, Ph), 7.68-7.71 (1H, m, Ph), 7.96 (1H, d, J = 5.1 Hz, Py), 8.09 (1H, s, NH), 11.69 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 5.31 (2H, s, OCH 2 Ph), 7.02-7.09 (2H, m, Py + Ph), 7.32 (2H, t, J = 7.5 Hz, Ph ), 7.38-7.43 (2H, m, Ph), 7.53-7.9 (4H, m, Ph), 7.68-7.71 (1H, m, Ph), 7.96 (1H, d, J = 5.1 Hz, Py), 8.09 (1H, s, NH), 11.69 (1H, s, NH)
화합물 28: 1-(3-(2-Compound 28: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.23 (2H, s, OCH2Ph), 6.89 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.13-7.15 (3H, m, Ph+Py), 7.31-7.34 (2H, m, Ph), 7.43-7.47 (2H, m, Ph), 7.48 (2H, d, J = 8.4 Hz, Ph), 7.50 (1H, s, NH), 7.87 (1H, dd, J1 = 1.2 Hz, J2 = 5.2 Hz, Py), 11.71 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.23 (2H, s, OCH 2 Ph), 6.89 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz , Py), 7.13-7.15 (3H, m, Ph + Py), 7.31-7.34 (2H, m, Ph), 7.43-7.47 (2H, m, Ph), 7.48 (2H, d, J = 8.4 Hz, Ph), 7.50 (1H, s, NH), 7.87 (1H, dd, J 1 = 1.2 Hz, J 2 = 5.2 Hz, Py), 11.71 (1H, s, NH)
화합물 29: 1-(3-(2-Compound 29: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.31 (2H, OCH2Ph), 7.07-7.11 (2H, m, Ph+Py), 7.34 (1H, t, J = 8.0 Hz, Ph), 7.40-7.43 (2H, m, Ph), 7.45-7.48 (2H, m, Ph), 7.53-7.57 (2H, m, Ph+Py), 7.68-7.70 (1H, m, Ph), 7.82 (1H, t, J = 2.0 Hz, Ph), 7.98 (1H, dd, J1 = 1.2 Hz, J2 = 4.8 Hz, Py), 8.24 (1H, s, NH), 11.82 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.31 (2H, OCH 2 Ph), 7.07-7.11 (2H, m, Ph + Py), 7.34 (1H, t, J = 8.0 Hz, Ph), 7.40-7.43 (2H, m, Ph), 7.45-7.48 (2H, m, Ph), 7.53-7.57 (2H, m, Ph + Py), 7.68-7.70 (1H, m, Ph), 7.82 (1H, t, J = 2.0 Hz, Ph), 7.98 (1H, dd, J 1 = 1.2 Hz, J 2 = 4.8 Hz, Py), 8.24 (1H, s, NH), 11.82 (1H, s, NH)
화합물 30: 1-(3-(2-Compound 30: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(4-(Pyridin-2-yl) -3- (4- ( 트리플루오르메틸Trifluoromethyl )페닐) ) Phenyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.25 (2H, s, OCH2Ph), 6.92 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.13 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 7.34-7.35 (2H, m, Ph), 7.45-7.46 (2H, m, Ph), 7.56-7.59 (3H, m, Ph+NH), 7.73 (2H, d, J = 8.8 Hz, Ph), 7.90 (1H, dd, J1 = 1.2, J2 = 5.2 Hz, Py), 12.14 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.25 (2H, s, OCH 2 Ph), 6.92 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.13 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py), 7.34-7.35 (2H, m, Ph), 7.45-7.46 (2H, m, Ph), 7.56-7.59 (3H, m, Ph + NH), 7.73 (2H, d, J = 8.8 Hz, Ph), 7.90 (1H, dd, J 1 = 1.2, J 2 = 5.2 Hz, Py), 12.14 (1H, s, NH)
화합물 31: 1-(3-(2-Compound 31: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.36 (2H, s, OCH2Ph), 7.15 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.42-7.44 (2H, m, Ph), 7.49-7.60 (3H, m, Ph), 7.62 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 7.66-7.74 (3H, m, Ph), 7.98 (1H, d, J = 8.0 Hz, Ph), 8.11 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 8.16-8.21 (2H, m, Ph), 12.38 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.36 (2H, s, OCH 2 Ph), 7.15 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.42-7.44 ( 2H, m, Ph), 7.49-7.60 (3H, m, Ph), 7.62 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py), 7.66-7.74 (3H, m, Ph), 7.98 (1H, d, J = 8.0 Hz, Ph), 8.11 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py), 8.16-8.21 (2H, m, Ph), 12.38 (1H, s, NH)
화합물 32: 1-(3-(3-Compound 32: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.27 (2H, s, OCH2Ph), 7.03-7.10 (2H, m, Ph), 7.18 (1H, t, J = 7.6 Hz, Ph), 7.26-7.31 (1H, m, Ph), 7.39-7.45 (2H, m, Py+Ph), 7.50-7.53 (2H, m, Ph), 7.70 (1H, s, Ph), 7.78 (1H, d, J = 5.2 Hz, Py), 8.65 (1H, s, NH), 12.06 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.27 (2H, s, OCH 2 Ph), 7.03-7.10 (2H, m, Ph), 7.18 (1H, t, J = 7.6 Hz, Ph), 7.26-7.31 (1H, m, Ph), 7.39-7.45 (2H, m, Py + Ph), 7.50-7.53 (2H, m, Ph), 7.70 (1H, s, Ph), 7.78 (1H, d, J = 5.2 Hz, Py), 8.65 (1H, s, NH), 12.06 (1H, s, NH)
화합물 33: 1-(3-(3-Compound 33: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.26 (2H, s, OCH2Ph), 6.84-6.89 (1H, m, Ph), 7.06 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.29-7.32 (1H, m, Ph), 7.35 (1H, d, J = 6.8 Hz, Ph), 7.38-7.45 (2H, m, Py+Ph), 7.49-7.52 (2H, m, Ph), 7.60-7.64 (1H, dt, J1= 2.4 Hz, J2 = 12.0 Hz, Ph), 7.69 (1H, s, Ph), 7.95 (1H, dd, J1 = 1.2 Hz, J2 = 5.2 Hz, Py), 8.54 (1H, s, NH), 11.87 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.26 (2H, s, OCH 2 Ph), 6.84-6.89 (1H, m, Ph), 7.06 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.29-7.32 (1H, m, Ph), 7.35 (1H, d, J = 6.8 Hz, Ph), 7.38-7.45 (2H, m, Py + Ph), 7.49-7.52 (2H , m, Ph), 7.60-7.64 (1H, dt, J 1 = 2.4 Hz, J 2 = 12.0 Hz, Ph), 7.69 (1H, s, Ph), 7.95 (1H, dd, J 1 = 1.2 Hz, J 2 = 5.2 Hz, Py), 8.54 (1H, s, NH), 11.87 (1H, s, NH)
화합물 34: 1-(3-(3-Compound 34: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3,4-Pyridin-2-yl) -3- (3,4- 다이클로로페닐Dichlorophenyl ) 유레아) Urea
1H NMR (400 MHz, CDCl3) δ = 5.11 (2H, s, OCH2Ph), 6.91 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.13 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 7.29-7.30 (1H, m, Ph), 7.36-7.38 (4H, m, Ph), 7.48 (1H, dd, J1 = 2.4 Hz, J2 = 8.8 Hz, Ph), 7.51 (1H, s, NH), 7.80 (1H, d, J = 2.4 Hz, Ph), 7.88 (1H, dd, J1 = 1.2 Hz, J2 = 5.2 Hz, Ph), 12.01 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.11 (2H, s, OCH 2 Ph), 6.91 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.13 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py), 7.29-7.30 (1H, m, Ph), 7.36-7.38 (4H, m, Ph), 7.48 (1H, dd, J 1 = 2.4 Hz, J 2 = 8.8 Hz, Ph), 7.51 (1H, s, NH), 7.80 (1H, d, J = 2.4 Hz, Ph), 7.88 (1H, dd, J 1 = 1.2 Hz, J 2 = 5.2 Hz, Ph ), 12.01 (1H, s, NH)
화합물 35: 1-(3-(3-Compound 35: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-벤질 ) Pyridin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 4.62 (2H, d, J = 7.2 Hz, OCH2Ph), 5.07 (2H, s, OCH2Ph), 6.80 (1H, dd, J1 = 4.8 Hz, J2 = 8.4 Hz, Py), 7.05 (1H, dd, J1 = 1.6 Hz, J2 = 8.4 Hz, Ph), 7.27-7.29 (1H, m, Ph), 7.32-7.39 (7H, m, Ph), 7.45 (1H, s, NH), 7.74 (1H, dd, J1 = 1.6 Hz, J2 = 4.8 Hz, Py), 9.90 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.62 (2H, d, J = 7.2 Hz, OCH 2 Ph), 5.07 (2H, s, OCH 2 Ph), 6.80 (1H, dd, J 1 = 4.8 Hz, J 2 = 8.4 Hz, Py), 7.05 (1H, dd, J 1 = 1.6 Hz, J 2 = 8.4 Hz, Ph), 7.27-7.29 (1H, m, Ph), 7.32-7.39 (7H, m, Ph) , 7.45 (1H, s, NH), 7.74 (1H, dd, J 1 = 1.6 Hz, J 2 = 4.8 Hz, Py), 9.90 (1H, s, NH)
화합물 36: 1-(3-(3-Compound 36: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.27 (2H, s, OCH2Ph), 7.02-7.05 (2H, m, Py+Ph), 7.33 (2H, t, J = 7.6 Hz, Ph), 7.41-7.44 (2H, m, Py+Ph), 7.48-7.51 (2H, m, Ph), 7.58 (2H, d, J = 8.0 Hz, Ph), 7.69 (1H, s, Ph), 7.94 (1H, d, J = 4.8 Hz, Py), 8.37 (1H, s, NH), 11.72 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.27 (2H, s, OCH 2 Ph), 7.02-7.05 (2H, m, Py + Ph), 7.33 (2H, t, J = 7.6 Hz, Ph ), 7.41-7.44 (2H, m, Py + Ph), 7.48-7.51 (2H, m, Ph), 7.58 (2H, d, J = 8.0 Hz, Ph), 7.69 (1H, s, Ph), 7.94 (1H, d, J = 4.8 Hz, Py), 8.37 (1H, s, NH), 11.72 (1H, s, NH)
화합물 37: 1-(3-(3-Compound 37: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.09 (2H, s, OCH2Ph), 6.87 (1H, dd, J1 = 4.8 Hz, J2 = 8.0 Hz, Py), 7.09 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 7.14 (2H, d, J = 8.4 Hz, Ph), 7.25-7.30 (1H, m, Ph), 7.35-7.36 (2H, m, Ph), 7.38 (1H, s, NH), 7.47 (2H, s, Ph), 7.49 (1H, s, Ph), 7.86 (1H, dd, J1 = 1.2 Hz, J2 = 4.8 Hz, Py), 11.71 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.09 (2H, s, OCH 2 Ph), 6.87 (1H, dd, J 1 = 4.8 Hz, J 2 = 8.0 Hz , Py), 7.09 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py), 7.14 (2H, d, J = 8.4 Hz, Ph), 7.25-7.30 (1H, m, Ph), 7.35-7.36 (2H, m, Ph), 7.38 (1H, s, NH), 7.47 (2H, s, Ph), 7.49 (1H, s, Ph), 7.86 (1H, dd, J 1 = 1.2 Hz, J 2 = 4.8 Hz, Py), 11.71 (1H, s, NH)
화합물 38: 1-(3-(3-Compound 38: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.26 (2H, OCH2Ph), 7.06 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.10 (1H, dd, J1 = 2.0 Hz, J2 = 8.0 Hz, Ph), 7.34 (1H, t, J = 8.0 Hz, Ph), 7.41-7.52 (5H, m, Ph+Py), 7.69 (1H, s, Ph), 7.83 (1H, t, J = 2.0 Hz. Ph), 7.95 (1H, d, J = 5.2 Hz, Py), 8.56 (1H, s, NH), 11.86 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.26 (2H, OCH 2 Ph), 7.06 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.10 (1H, dd, J 1 = 2.0 Hz, J 2 = 8.0 Hz, Ph), 7.34 (1H, t, J = 8.0 Hz, Ph), 7.41-7.52 (5H, m, Ph + Py), 7.69 (1H, s, Ph) , 7.83 (1H, t, J = 2.0 Hz.Ph), 7.95 (1H, d, J = 5.2 Hz, Py), 8.56 (1H, s, NH), 11.86 (1H, s, NH)
화합물 39: 1-(3-(3-Compound 39: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(4-(Pyridin-2-yl) -3- (4- ( 트리플루오르메틸Trifluoromethyl )페닐) ) Phenyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.11 (2H, s, OCH2Ph), 6.92 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.13 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 7.28-7.31 (1H, m, Ph), 7.36-7.39 (3H, m, Ph), 7.54 (1H, s, NH), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 8.89 (1H, dd, J1 = 1.2, J2 = 5.2 Hz, Py), 11.71 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.11 (2H, s, OCH 2 Ph), 6.92 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.13 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py), 7.28-7.31 (1H, m, Ph), 7.36-7.39 (3H, m, Ph), 7.54 (1H, s, NH), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 8.89 (1H, dd, J 1 = 1.2, J 2 = 5.2 Hz, Py), 11.71 (1H, s, NH)
화합물 40: 1-(3-(3-Compound 40: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 5.31 (2H, s, OCH2Ph), 7.11 (1H, dd, J1 = 8.1 Hz, J2 = 5.1 Hz, Py), 7.43-7.45 (2H, m, Ph+Py), 7.48-7.60 (4H, m, Ph), 7.66-7.73 (3H, m, Ph), 7.97 (1H, d, J = 7.2 Hz, Py), 8.08 (1H, d, J = 5.4 Hz, Ph), 8.17 (1H, d, J = 8.4 Hz, Ph), 8.22 (1H, d, J = 7.8 Hz, Ph), 8.63 (1H, s, NH), 12.45 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 5.31 (2H, s, OCH 2 Ph), 7.11 (1H, dd, J 1 = 8.1 Hz, J 2 = 5.1 Hz, Py), 7.43-7.45 ( 2H, m, Ph + Py), 7.48-7.60 (4H, m, Ph), 7.66-7.73 (3H, m, Ph), 7.97 (1H, d, J = 7.2 Hz, Py), 8.08 (1H, d , J = 5.4 Hz, Ph), 8.17 (1H, d, J = 8.4 Hz, Ph), 8.22 (1H, d, J = 7.8 Hz, Ph), 8.63 (1H, s, NH), 12.45 (1H, s, NH)
화합물 41: 1-(3-(4-Compound 41: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.10 (2H, s, OCH2Ph), 6.88 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.01-7.03 (1H, m, Ph), 7.08-7.15 (3H, m, Ph+ Py), 7.34 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, dd, J = 8.4 Hz, Ph), 7.52 (1H, s, NH), 7.90 (1H, dd, J1 = 4.8 Hz, J2 = 8.0 Hz, Py), 8.30-8.34 (1H, m, Ph), 12.19 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.10 (2H, s, OCH 2 Ph), 6.88 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.01-7.03 (1H, m, Ph), 7.08-7.15 (3H, m, Ph + Py), 7.34 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, dd, J = 8.4 Hz, Ph), 7.52 (1H, s , NH), 7.90 (1H, dd, J 1 = 4.8 Hz, J 2 = 8.0 Hz, Py), 8.30-8.34 (1H, m, Ph), 12.19 (1H, s, NH)
화합물 42: 1-(3-(4-Compound 42: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.10 (2H, s, OCH2Ph), 6.74-6.79 (1H, m, Ph), 6.89 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.12 (1H ,dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.23-7.29 (2H, m, Ph), 7.33 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, d, J = 8.4 Hz, Ph), 7.49 (1H, s, NH), 7.51-7.55 (1H, m, Ph), 7.86 (1H, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 11.97 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.10 (2H, s, OCH 2 Ph), 6.74-6.79 (1H, m, Ph), 6.89 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.12 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.23-7.29 (2H, m, Ph), 7.33 (2H, d, J = 8.4 Hz, Ph) , 7.40 (2H, d, J = 8.4 Hz, Ph), 7.49 (1H, s, NH), 7.51-7.55 (1H, m, Ph), 7.86 (1H, J 1 = 5.2 Hz, J 2 = 1.2 Hz , Py), 11.97 (1H, s, NH)
화합물 43: 1-(3-(4-Compound 43: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3,4-Pyridin-2-yl) -3- (3,4- 다이클로로페닐Dichlorophenyl ) 유레아) Urea
1H NMR (400 MHz, CDCl3) δ = 5.10 (2H, s, OCH2Ph), 6.90 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.13 (1H ,dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.32-7.35 (3H, m, Ph), 7.38-7.41 (3H, m, Ph), 7.47 (1H, dd, J1 = 8.8 Hz, J2 = 2.4 Hz, Ph), 7.51 (1H, s, NH), 7.80 (1H, d, J = 2.4 Hz, Ph), 7.87 (1H, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 12.00 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.10 (2H, s, OCH 2 Ph), 6.90 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.13 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.32-7.35 (3H, m, Ph), 7.38-7.41 (3H, m, Ph), 7.47 (1H, dd, J 1 = 8.8 Hz, J 2 = 2.4 Hz, Ph), 7.51 (1H, s, NH), 7.80 (1H, d, J = 2.4 Hz, Ph), 7.87 (1H, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 12.00 (1H, s, NH)
화합물 44: 1-(3-(4-Compound 44: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 2.26 (3H, s, CH3), 5.25 (2H, s, OCH2Ph), 7.02 (1H, dd, J1 = 8.1 Hz, J2 = 5.1 Hz, Py), 7.13 (2H, d, J = 8.1 Hz, Ph), 7.44-7.49 (5H, m, Py+Ph), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.91 (1H, d, J = 5.1 Hz, Ph), 8.18 (1H, s, NH), 11.64 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 2.26 (3H, s, CH 3 ), 5.25 (2H, s, OCH 2 Ph), 7.02 (1H, dd, J 1 = 8.1 Hz, J 2 = 5.1 Hz, Py), 7.13 (2H, d, J = 8.1 Hz, Ph), 7.44-7.49 (5H, m, Py + Ph), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.91 (1H , d, J = 5.1 Hz, Ph), 8.18 (1H, s, NH), 11.64 (1H, s, NH)
화합물 45: 1-(3-(4-Compound 45: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.10 (2H, s, OCH2Ph), 6.90 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.03-7.06 (1H, m, Ph), 7.12 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.24 (1H, t, J = 8.4 Hz, Ph), 7.34 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, d, J = 8.4 Hz, Ph), 7.48-7.50 (2H, m, Ph+NH), 7.68 (1H, t, J = 2.4 Hz, Ph), 7.87 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 11.95 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.10 (2H, s, OCH 2 Ph), 6.90 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.03-7.06 (1H, m, Ph), 7.12 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.24 (1H, t, J = 8.4 Hz, Ph), 7.34 (2H, d, J = 8.4 Hz, Ph ), 7.40 (2H, d, J = 8.4 Hz, Ph), 7.48-7.50 (2H, m, Ph + NH), 7.68 (1H, t, J = 2.4 Hz, Ph), 7.87 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 11.95 (1H, s, NH)
화합물 46: 1-(3-(4-Compound 46: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(4-(Pyridin-2-yl) -3- (4- ( 트리플루오르메틸Trifluoromethyl )페닐) ) Phenyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.11 (2H, s, OCH2Ph), 6.90 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.13 (1H ,dd, J1 = 8.0 Hz, J2 = 0.8 Hz, Py), 7.34 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, d, J = 8.4 Hz, Ph), 7.52 (1H, s, NH), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 7.88 (1H, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 12.12 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.11 (2H, s, OCH 2 Ph), 6.90 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.13 (1H, dd, J 1 = 8.0 Hz, J 2 = 0.8 Hz, Py), 7.34 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, d, J = 8.4 Hz, Ph), 7.52 (1H, s, NH ), 7.58 (2H, d, J = 8.4 Hz, Ph), 7.73 (2H, d, J = 8.4 Hz, Ph), 7.88 (1H, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 12.12 (1H, s, NH)
화합물 47: 1-(3-(4-Compound 47: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.14 (2H, s, OCH2Ph), 6.93 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.16 (1H, d, J = 8.0 Hz, Py), 7.37 (2H, d, J = 8.4 Hz, Ph), 7.41 (2H, d, J = 8.4 Hz, Ph), 7.49-7.57 (3H, m, Ph), 7.63 (1H, brs, Ph), 7.65 (1H, s, NH), 7.87 (1H, d, J = 8.0 Hz, Ph), 7.98 (1H, d, J = 5.2 Hz, Py), 8.22 (2H, d, J = 7.6 Hz, Ph), 12.39 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.14 (2H, s, OCH 2 Ph), 6.93 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.16 (1H, d, J = 8.0 Hz, Py), 7.37 (2H, d, J = 8.4 Hz, Ph), 7.41 (2H, d, J = 8.4 Hz, Ph), 7.49-7.57 (3H, m, Ph), 7.63 (1H , brs, Ph), 7.65 (1H, s, NH), 7.87 (1H, d, J = 8.0 Hz, Ph), 7.98 (1H, d, J = 5.2 Hz, Py), 8.22 (2H, d, J = 7.6 Hz, Ph), 12.39 (1H, s, NH)
실시예Example 2. 1-(3-(3- 2. 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(Pyridin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
3-(3-플루오르벤질옥시)피리딘-2-아민 (350 mg, 1.60 mmol)과 수소화나트륨 (60% in mineral oil, 128 mg, 3.2 mmol)을 테트라하이드로퓨란 (0.25M)에 녹인 후, 1-아다만틸 아이소시아네이트 (341.09 mg, 1.92 mmol)를 적가 한 후 20시간 동안 가열 환류 시킨다. 반응물을 실온까지 식히고 물을 넣어 반응을 종결시킨 다음, 초산에틸로 추출한다. 추출한 용액을 황산나트륨으로 건조시킨 후 감압 여과하여 감압 농축한다. 잔여물을 컬럼크로마토그래피법 (초산에틸/노르말헥산 =1/2)으로 분리 정제하여 60.23 %의 수율로 목적화합물 382 mg을 얻었다.Dissolve 3- (3-fluorobenzyloxy) pyridin-2-amine (350 mg, 1.60 mmol) and sodium hydride (60% in mineral oil, 128 mg, 3.2 mmol) in tetrahydrofuran (0.25M), then 1 -Adamantyl isocyanate (341.09 mg, 1.92 mmol) is added dropwise and heated to reflux for 20 hours. The reaction is cooled to room temperature, water is added to terminate the reaction, and extracted with ethyl acetate. The extracted solution was dried over sodium sulfate, filtered under reduced pressure and concentrated under reduced pressure. The residue was separated and purified by column chromatography (ethyl acetate / normal hexane = 1/2) to obtain 382 mg of the target compound in a yield of 60.23%.
1H NMR (400 MHz, CDCl3) δ = 1.71 (4H, s, adamantyl), 1.94 (2H, s, adamantyl), 2.11 (8H, s, adamantyl), 5.08 (2H, s, OCH2Ph), 6.75 (1H, dd, J1 = 5.07 Hz, J2 = 7.92 Hz, Py), 7.00-7.08 (3H, m, Py+ Ph), 7.15 (1H, s, NH), 7.17 (1H, s, Ph), 7.35-7.37 (1H, m, Ph), 7.74 (1H, d, J = 5.07 Hz, Py), 9.39 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.71 (4H, s, adamantyl), 1.94 (2H, s, adamantyl), 2.11 (8H, s, adamantyl), 5.08 (2H, s, OCH 2 Ph), 6.75 (1H, dd, J 1 = 5.07 Hz, J 2 = 7.92 Hz, Py), 7.00-7.08 (3H, m, Py + Ph), 7.15 (1H, s, NH), 7.17 (1H, s, Ph) , 7.35-7.37 (1H, m, Ph), 7.74 (1H, d, J = 5.07 Hz, Py), 9.39 (1H, s, NH)
이하, 하기 화합물 48 내지 75를 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
The following compounds 48 to 75 were obtained by the same method as the above examples, and the analysis results of these compounds were as follows:
화합물 48: 1-(3-(Compound 48: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(Pyridin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.72 (4H, s, adamantyl), 1.94 (2H, s, adamantyl), 2.11 (8H, s, adamantyl), 5.09 (2H, s, OCH2Ph), 6.77-6.74 (1H, dd, J1 = 5.13 Hz, J2 = 7.93 Hz, Py), 7.04 (1H, d, J = 7.92 Hz, Py), 7.19 (1H, s, NH), 7.37-7.41 (5H, m, Ph), 7.73 (1H, dd, J1 = 1.14 Hz, J2 = 4.99 Hz, Py), 9.41 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.72 (4H, s, adamantyl), 1.94 (2H, s, adamantyl), 2.11 (8H, s, adamantyl), 5.09 (2H, s, OCH 2 Ph), 6.77-6.74 (1H, dd, J 1 = 5.13 Hz, J 2 = 7.93 Hz, Py), 7.04 (1H, d, J = 7.92 Hz, Py), 7.19 (1H, s, NH), 7.37-7.41 ( 5H, m, Ph), 7.73 (1H, dd, J 1 = 1.14 Hz, J 2 = 4.99 Hz, Py), 9.41 (1H, s, NH)
화합물 49: 1-(3-(Compound 49: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.56-1.66 (10H, m, Cycloheptyl), 1.95-2.00 (2H, m, Cycloheptyl), 4.01-4.03 (1H, m, Cycloheptyl), 5.09 (2H, s, OCH2Ph), 6.79-6.76 (1H, dd, J1 = 5.10 Hz, J2 = 7.91 Hz, Py), 7.06 (1H, d, J = 7.95 Hz, Py), 7.33 (1H, s, NH), 7.35-7.39 (5H, m, Ph), 7.76 (1H, d, J = 5.08 Hz, Py), 9.53 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.56-1.66 (10H, m, Cycloheptyl), 1.95-2.00 (2H, m, Cycloheptyl), 4.01-4.03 (1H, m, Cycloheptyl), 5.09 (2H, s , OCH 2 Ph), 6.79-6.76 (1H, dd, J 1 = 5.10 Hz, J 2 = 7.91 Hz, Py), 7.06 (1H, d, J = 7.95 Hz, Py), 7.33 (1H, s, NH ), 7.35-7.39 (5H, m, Ph), 7.76 (1H, d, J = 5.08 Hz, Py), 9.53 (1H, s, NH)
화합물 50: 1-(3-(Compound 50: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(2,4,4-) Pyridin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.00 (2H, s, CH2), 1.02 (9H, s, 3CH3), 1.35 (2H, s, CH2), 1.55 (2H, s, CH2), 1.81 (2H, s, CH2), 5.08 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 5.12 Hz, J2 = 7.98 Hz, Py), 7.05 (1H, dd, J1 = 1.35 Hz, J2 = 7.98 Hz, Py), 7.21 (1H, s, NH), 7.35-7.39 (5H, m, Ph), 7.73 (1H, dd, J1 = 1.35 Hz, J2 = 5.12 Hz, Py), 9.51 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.00 (2H, s, CH 2 ), 1.02 (9H, s, 3CH 3 ), 1.35 (2H, s, CH 2 ), 1.55 (2H, s, CH 2 ), 1.81 (2H, s, CH 2 ), 5.08 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 5.12 Hz, J 2 = 7.98 Hz, Py), 7.05 (1H, dd, J 1 = 1.35 Hz, J 2 = 7.98 Hz, Py), 7.21 (1H, s, NH), 7.35-7.39 (5H, m, Ph), 7.73 (1H, dd, J 1 = 1.35 Hz, J 2 = 5.12 Hz, Py), 9.51 (1H, s, NH)
화합물 51: 1-(3-(Compound 51: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.25 (3H, t, J = 7.20 Hz, CH3), 3.40-3.43 (2H, m, CH2), 5.09 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.05 Hz, J2 = 7.96 Hz, Py), 7.07 (1H, dd, J1 = 1.16 Hz, J2 = 7.96 Hz, Py), 7.36-7.42 (6H, m, Ph+NH), 7.76 (1H, dd, J1 = 1.16 Hz, J2 = 5.05 Hz, Py), 9.42 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.25 (3H, t, J = 7.20 Hz, CH 3 ), 3.40-3.43 (2H, m, CH 2 ), 5.09 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.05 Hz, J 2 = 7.96 Hz, Py), 7.07 (1H, dd, J 1 = 1.16 Hz, J 2 = 7.96 Hz, Py), 7.36-7.42 (6H, m, Ph + NH), 7.76 (1H, doublet of doublets, J 1 = 1.16 Hz, J 2 = 5.05 Hz, Py), 9.42 (1H, s, NH)
화합물 52: 1-(3-(Compound 52: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.44 (9H, s, 3CH3), 5.09 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 5.07 Hz, J2 = 7.96 Hz, Py), 7.05 (1H, dd, J1 = 1.27 Hz, J2 = 7.96 Hz, Py), 7.23 (1H, s, NH), 7.35-7.39 (5H, m, Ph), 7.74 (1H, dd, J1 = 1.27 Hz, J2 = 5.07 Hz, Py), 9.46 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.44 (9H, s, 3CH 3 ), 5.09 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 5.07 Hz, J 2 = 7.96 Hz , Py), 7.05 (1H, dd, J 1 = 1.27 Hz, J 2 = 7.96 Hz, Py), 7.23 (1H, s, NH), 7.35-7.39 (5H, m, Ph), 7.74 (1H, dd) , J 1 = 1.27 Hz, J 2 = 5.07 Hz, Py), 9.46 (1H, s, NH)
화합물 53: 1-(3-(3-Compound 53: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(Pyridin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.71 (4H, s, adamantyl), 1.94 (2H, s, adamantyl), 2.11 (8H, s, adamantyl), 5.08 (2H, s, OCH2Ph), 6.75 (1H, dd, J1 = 5.07 Hz, J2 = 7.92 Hz, Py), 7.00-7.08 (3H, m, Py+ Ph), 7.15 (1H, s, NH), 7.17 (1H, s, Ph), 7.35-7.37 (1H, m, Ph), 7.74 (1H, d, J = 5.07 Hz, Py), 9.39 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.71 (4H, s, adamantyl), 1.94 (2H, s, adamantyl), 2.11 (8H, s, adamantyl), 5.08 (2H, s, OCH 2 Ph), 6.75 (1H, dd, J 1 = 5.07 Hz, J 2 = 7.92 Hz, Py), 7.00-7.08 (3H, m, Py + Ph), 7.15 (1H, s, NH), 7.17 (1H, s, Ph) , 7.35-7.37 (1H, m, Ph), 7.74 (1H, d, J = 5.07 Hz, Py), 9.39 (1H, s, NH)
화합물 54: 1-(3-(3-Compound 54: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.57-1.68 (10H, m, Cycloheptyl), 1.95-2.01 (2H, m, Cycloheptyl), 4.02-4.04 (1H, m, Cycloheptyl), 5.08 (2H, s, OCH2Ph), 6.78 (1H, dd, J1 = 5.10 Hz, J2 = 8.0 Hz, Py), 7.03 (1H, dd, J1 = 1.32 Hz, J2 = 8.0 Hz, Py), 7.06-7.09 (2H, m, Ph), 7.16 (1H, d, J = 7.74 Hz, Ph), 7.31 (1H, s, NH), 7.34-7.39 (1H, m, Ph), 7.78 (1H, dd, J1 = 1.32 Hz, J2 = 5.10 Hz, Py), 9.51 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.57-1.68 (10H, m, Cycloheptyl), 1.95-2.01 (2H, m, Cycloheptyl), 4.02-4.04 (1H, m, Cycloheptyl), 5.08 (2H, s , OCH 2 Ph), 6.78 (1H, dd, J 1 = 5.10 Hz, J 2 = 8.0 Hz, Py), 7.03 (1H, dd, J 1 = 1.32 Hz, J 2 = 8.0 Hz, Py), 7.06- 7.09 (2H, m, Ph), 7.16 (1H, d, J = 7.74 Hz, Ph), 7.31 (1H, s, NH), 7.34-7.39 (1H, m, Ph), 7.78 (1H, dd, J 1 = 1.32 Hz, J 2 = 5.10 Hz, Py), 9.51 (1H, s, NH)
화합물 55: 1-(3-(3-Compound 55: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2,4,4-) Pyridin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.00 (4H, s, CH2), 1.03 (9H, s, 3CH3), 1.34 (2H, s, CH2), 1.81 (2H, s, CH2), 5.07 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 5.10 Hz, J2 = 7.93 Hz, Py), 7.02 (1H, dd, J1 = 1.2 Hz, J2 = 7.93 Hz, Py), 704-7.09 (2H, m, Ph), 7.16 (2H, d, J = 7.71 Hz, Ph), 7.18 (1H, s, NH), 7.33-7.37 (1H, m, Ph), 7.75 (1H, dd, J1 = 1.2 Hz, J2 = 5.10 Hz, Py), 9.50 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.00 (4H, s, CH 2), 1.03 (9H, s, 3CH 3 ), 1.34 (2H, s, CH 2 ), 1.81 (2H, s, CH 2 ) , 5.07 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 5.10 Hz, J 2 = 7.93 Hz, Py), 7.02 (1H, dd, J 1 = 1.2 Hz, J 2 = 7.93 Hz , Py), 704-7.09 (2H, m, Ph), 7.16 (2H, d, J = 7.71 Hz, Ph), 7.18 (1H, s, NH), 7.33-7.37 (1H, m, Ph), 7.75 (1H, dd, J 1 = 1.2 Hz, J 2 = 5.10 Hz, Py), 9.50 (1H, s, NH)
화합물 56: 1-(3-(3-Compound 56: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.25 (3H, t, J = 7.20 Hz, CH3), 3.40-3.44 (2H, m, CH2), 5.08 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.13 Hz, J2 = 7.95 Hz, Py), 7.03-7.08 (3H, m, Py+Ph), 7.16 (1H, d, J = 7.64 Hz, Ph), 7.34-7.38 (2H, m, Ph+NH), 7.77-7.78 (1H, m, Py), 9.42 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.25 (3H, t, J = 7.20 Hz, CH 3 ), 3.40-3.44 (2H, m, CH 2 ), 5.08 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J1 = 5.13 Hz, J2 = 7.95 Hz, Py), 7.03-7.08 (3H, m, Py + Ph), 7.16 (1H, d, J = 7.64 Hz, Ph), 7.34-7.38 ( 2H, m, Ph + NH), 7.77-7.78 (1H, m, Py), 9.42 (1H, s, NH)
화합물 57: 1-(3-(3-Compound 57: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.46 (9H, s, 3CH3), 5.08 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 5.10 Hz, J2 = 7.99 Hz, Py), 7.02 (1H, dd, J1 = 1.32 Hz, J2 = 7.99 Hz, Py), 7.04-7.09 (2H, m, Ph), 7.16 (1H, d, J = 7.62 Hz, Ph), 7.20 (1H, s, NH), 7.33-7.39 (1H, m, Ph), 7.75 (1H, dd, J1 = 1.32 Hz, J2 = 5.10 Hz, Py), 9.45 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.46 (9H, s, 3CH 3 ), 5.08 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 5.10 Hz, J 2 = 7.99 Hz , Py), 7.02 (1H, dd, J 1 = 1.32 Hz, J 2 = 7.99 Hz, Py), 7.04-7.09 (2H, m, Ph), 7.16 (1H, d, J = 7.62 Hz, Ph), 7.20 (1H, s, NH), 7.33-7.39 (1H, m, Ph), 7.75 (1H, dd, J 1 = 1.32 Hz, J 2 = 5.10 Hz, Py), 9.45 (1H, s, NH)
화합물 58: 1-(3-(4-Compound 58: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.58-1.65 (10H, m, Cycloheptyl), 1.96-1.99 (2H, m, Cycloheptyl), 4.01-4.04 (1H, m, Cycloheptyl), 5.04 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.04-7.11 (3H, m, Ph+Py), 7.30 (1H, s, NH), 7.34-7.37 (2H, m, Ph), 7.77 (1H, d, J = 4.8 Hz, Py), 9.52 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.58-1.65 (10H, m, Cycloheptyl), 1.96-1.99 (2H, m, Cycloheptyl), 4.01-4.04 (1H, m, Cycloheptyl), 5.04 (2H, s , OCH 2 Ph), 6.79 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.04-7.11 (3H, m, Ph + Py), 7.30 (1H, s, NH), 7.34 -7.37 (2H, m, Ph), 7.77 (1H, d, J = 4.8 Hz, Py), 9.52 (1H, s, NH)
화합물 59: 1-(3-(4-Compound 59: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2,4,4-) Pyridin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.02 (9H, s, 3CH3), 1.48 (6H, s, 2CH3), 1.81 (2H, CH2), 5.03 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.04 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.08 (2H, d, J = 8.4 Hz, Ph), 7.17 (1H, s, NH), 7.34-7.38 (2H, m, Ph), 7.74 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 9.50 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.02 (9H, s, 3CH 3 ), 1.48 (6H, s, 2CH 3 ), 1.81 (2H, CH 2 ), 5.03 (2H, s, OCH 2 Ph) , 6.77 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.04 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.08 (2H, d, J = 8.4 Hz, Ph), 7.17 (1H, s, NH), 7.34-7.38 (2H, m, Ph), 7.74 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 9.50 ( 1H, s, NH)
화합물 60: 1-(3-(4-Compound 60: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.24 (3H, t, J = 7.2 Hz, CH3), 3.38-3.45 (2H, m, CH2), 5.04 (2H, s, OCH2Ph), 6.80 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.05-7.12 (3H, m, Ph+Py), 7.34-7.38 (3H, m, Ph+NH), 7.77 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 9.41 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.24 (3H, t, J = 7.2 Hz, CH 3 ), 3.38-3.45 (2H, m, CH 2 ), 5.04 (2H, s, OCH 2 Ph), 6.80 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.05-7.12 (3H, m, Ph + Py), 7.34-7.38 (3H, m, Ph + NH), 7.77 (1H , dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 9.41 (1H, s, NH)
화합물 61: 1-(3-(4-Compound 61: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.44 (9H, s, 3CH3), 5.04 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.03-7.08 (3H, m, Ph+Py), 7.10 (1H, s, NH), 7.34-7.37 (2H, m, Ph), 7.74 (1H, dd, J1 = 4.8 Hz, J2 = 1.2 Hz, Py), 9.44 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.44 (9H, s, 3CH 3 ), 5.04 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz , Py), 7.03-7.08 (3H, m, Ph + Py), 7.10 (1H, s, NH), 7.34-7.37 (2H, m, Ph), 7.74 (1H, dd, J 1 = 4.8 Hz, J 2 = 1.2 Hz, Py), 9.44 (1H, s, NH)
화합물 62: 1-(3-(2-Compound 62: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(Pyridin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.64-1.72 (4H, m, adamantyl), 1.94 (1H, m, adamantyl), 2.11 (9H, s, adamantyl), 5.20 (2H, s, OCH2Ph), 6.78 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.05 (1H, J1 = 1.32 Hz, J2 = 8.0 Hz, Py), 7.19 (1H, s, NH), 7.28-7.31 (2H, m, Ph), 7.41-7.43 (2H, m, Ph), 7.75 (1H, dd, J1 = 1.32 Hz, J2 = 5.12 Hz, Py), 9.40 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.64-1.72 (4H, m, adamantyl), 1.94 (1H, m, adamantyl), 2.11 (9H, s, adamantyl), 5.20 (2H, s, OCH 2 Ph ), 6.78 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz, Py), 7.05 (1H, J 1 = 1.32 Hz, J 2 = 8.0 Hz, Py), 7.19 (1H, s, NH) , 7.28-7.31 (2H, m, Ph), 7.41-7.43 (2H, m, Ph), 7.75 (1H, dd, J 1 = 1.32 Hz, J 2 = 5.12 Hz, Py), 9.40 (1H, s, NH)
화합물 63: 1-(3-(2-Compound 63: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.56-1.68 (10H, m, Cycloheptyl), 1.97-1.98 (2H, m, Cycloheptyl), 4.01-4.05 (1H, m, Cycloheptyl), 5.20 (2H, s, OCH2Ph), 6.81 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.07 (1H, dd, J1 = 1.32 Hz, J2 = 8.0 Hz, Py), 7.28-7.32 (2H, m, Ph), 7.33 (1H, s, NH), 7.41-7.44 (2H, m, Ph), 7.78 (1H, dd, J1 = 1.32 Hz, J2 = 5.12 Hz, Py), 9.52 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.56-1.68 (10H, m, Cycloheptyl), 1.97-1.98 (2H, m, Cycloheptyl), 4.01-4.05 (1H, m, Cycloheptyl), 5.20 (2H, s , OCH 2 Ph), 6.81 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz, Py), 7.07 (1H, dd, J 1 = 1.32 Hz, J 2 = 8.0 Hz, Py), 7.28- 7.32 (2H, m, Ph), 7.33 (1H, s, NH), 7.41-7.44 (2H, m, Ph), 7.78 (1H, dd, J 1 = 1.32 Hz, J 2 = 5.12 Hz, Py), 9.52 (1 H, s, NH)
화합물 64: 1-(3-(2-Compound 64: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2,4,4-) Pyridin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.03 (9H, s, 3CH3), 1.49 (6H, s, 2CH3), 1.82 (2H, s, CH2), 5.19 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.04 (1H, dd, J1 = 1.28 Hz, J2 = 8.0 Hz, Py), 7.21 (1H, s, NH), 7.29-7.32 (2H, m, Ph), 7.41-7.45 (2H, m, Ph), 7.75 (1H, dd, J1 = 1.28 Hz, J2 = 5.12 Hz, Py), 9.51 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.03 (9H, s, 3CH 3 ), 1.49 (6H, s, 2CH 3 ), 1.82 (2H, s, CH 2 ), 5.19 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz, Py), 7.04 (1H, dd, J 1 = 1.28 Hz, J 2 = 8.0 Hz, Py), 7.21 (1H, s , NH), 7.29-7.32 (2H, m, Ph), 7.41-7.45 (2H, m, Ph), 7.75 (1H, dd, J 1 = 1.28 Hz, J 2 = 5.12 Hz, Py), 9.51 (1H , s, NH)
화합물 65: 1-(3-(2-Compound 65: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.25 (3H, t, J = 7.24 Hz, CH3), 3.39-3.46 (2H, m, CH2), 5.20 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.04 (1H, dd, J1 = 1.28 Hz, J2 = 8.0 Hz, Py), 7.30-7.34 (2H, m, Ph), 7.38 (1H, s, NH), 7.41-7.44 (2H, m, Ph), 7.78 (1H, dd, J1 = 1.28 Hz, J2 = 5.12 Hz, Py), 9.42 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.25 (3H, t, J = 7.24 Hz, CH 3 ), 3.39-3.46 (2H, m, CH 2 ), 5.20 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz, Py), 7.04 (1H, dd, J 1 = 1.28 Hz, J 2 = 8.0 Hz, Py), 7.30-7.34 (2H, m, Ph), 7.38 (1H, s, NH), 7.41-7.44 (2H, m, Ph), 7.78 (1H, dd, J 1 = 1.28 Hz, J 2 = 5.12 Hz, Py), 9.42 (1H, s, NH)
화합물 66: 1-(3-(2-Compound 66: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.44 (9H, s, 3CH3), 5.19 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.06 (1H, dd, J1 = 1.6 Hz, J2 = 8.0 Hz, Py), 7.23 (1H, s, NH), 7.28-7.31 (2H, m, Ph), 7.41-7.44 (2H, m, Ph), 7.76 (1H, dd, J1 = 1.6 Hz, J2 = 5.12 Hz, Py), 9.46 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.44 (9H, s, 3CH 3 ), 5.19 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz , Py), 7.06 (1H, dd, J 1 = 1.6 Hz, J 2 = 8.0 Hz, Py), 7.23 (1H, s, NH), 7.28-7.31 (2H, m, Ph), 7.41-7.44 (2H , m, Ph), 7.76 (1H, dd, J 1 = 1.6 Hz, J 2 = 5.12 Hz, Py), 9.46 (1H, s, NH)
화합물 67: 1-(3-(3-Compound 67: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(Pyridin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.69-1.75 (4H, m, adamantyl), 1.94 (1H, m, adamantyl), 2.11 (9H, s, adamantyl), 5.06 (2H, s, OCH2Ph), 6.75 (1H, dd, J1 = 5.12 Hz, J2 = 7.96 Hz, Py), 7.00 (1H, J1 = 1.36 Hz, J2 = 7.96 Hz, Py), 7.16 (1H, s, NH), 7.27-7.28 (1H, m, Ph), 7.32-7.35 (2H, m, Ph), 7.36 (1H, s, Ph), 7.74 (1H, dd, J1 = 1.36 Hz, J2 = 5.12 Hz, Py), 9.39 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3) δ = 1.69-1.75 (4H, m, adamantyl), 1.94 (1H, m, adamantyl), 2.11 (9H, s, adamantyl), 5.06 (2H, s, OCH 2 Ph ), 6.75 (1H, dd, J 1 = 5.12 Hz, J 2 = 7.96 Hz, Py), 7.00 (1H, J 1 = 1.36 Hz, J 2 = 7.96 Hz, Py), 7.16 (1H, s, NH) , 7.27-7.28 (1H, m, Ph ), 7.32-7.35 (2H, m, Ph), 7.36 (1H, s, Ph), 7.74 (1H, dd, J 1 = 1.36 Hz, J 2 = 5.12 Hz, Py), 9.39 (1H, s, NH)
화합물 68: 1-(3-(3-Compound 68: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.56-1.67 (10H, m, Cycloheptyl), 1.97-2.04 (2H, m, Cycloheptyl), 4.01-4.03 (1H, m, Cycloheptyl), 5.06 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.14 Hz, J2 = 8.0 Hz, Py), 7.02 (1H, dd, J1 = 1.32 Hz, J2 = 8.0 Hz, Py), 7.27-7.28 (1H, m, Ph), 7.30 (1H, s, NH), 7.33-7.36 (3H, m, Ph), 7.78 (1H, dd, J1 = 1.32 Hz, J2 = 5.14 Hz, Py), 9.52 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.56-1.67 (10H, m, Cycloheptyl), 1.97-2.04 (2H, m, Cycloheptyl), 4.01-4.03 (1H, m, Cycloheptyl), 5.06 (2H, s , OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.14 Hz, J 2 = 8.0 Hz, Py), 7.02 (1H, dd, J 1 = 1.32 Hz, J 2 = 8.0 Hz, Py), 7.27- 7.28 (1H, m, Ph), 7.30 (1H, s, NH), 7.33-7.36 (3H, m, Ph), 7.78 (1H, dd, J 1 = 1.32 Hz, J 2 = 5.14 Hz, Py), 9.52 (1 H, s, NH)
화합물 69: 1-(3-(3-Compound 69: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2,4,4-) Pyridin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.03 (9H, s, 3CH3), 1.49 (6H, s, 2CH3), 1.81 (2H, s, CH2), 5.05 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 5.12 Hz, J2 = 7.96 Hz, Py), 7.01 (1H, dd, J1 = 1.32 Hz, J2 = 7.96 Hz, Py), 7.17 (1H, s, NH), 7.27-7.28 (1H, m, Ph), 7.32-7.36 (3H, m, Ph), 7.75 (1H, dd, J1 = 1.32 Hz, J2 = 5.12 Hz, Py), 9.50 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.03 (9H, s, 3CH 3 ), 1.49 (6H, s, 2CH 3 ), 1.81 (2H, s, CH 2 ), 5.05 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 5.12 Hz, J 2 = 7.96 Hz, Py), 7.01 (1H, dd, J 1 = 1.32 Hz, J 2 = 7.96 Hz, Py), 7.17 (1H, s , NH), 7.27-7.28 (1H, m, Ph), 7.32-7.36 (3H, m, Ph), 7.75 (1H, dd, J 1 = 1.32 Hz, J 2 = 5.12 Hz, Py), 9.50 (1H , s, NH)
화합물 70: 1-(3-(3-Compound 70: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.25 (3H, t, J = 7.04 Hz, CH3), 3.38-3.45 (2H, m, CH2), 5.06 (2H, s, OCH2Ph), 6.79 (1H, dd, J1 = 5.12 Hz, J2 = 7.96 Hz, Py), 7.04 (1H, dd, J1 = 1.32 Hz, J2 = 7.96 Hz, Py), 7.26-7.28 (1H, m, Ph), 7.33-7.36 (4H, m, Ph+NH), 7.78 (1H, dd, J1 = 1.32 Hz, J2 = 5.12 Hz, Py), 9.40 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.25 (3H, t, J = 7.04 Hz, CH 3 ), 3.38-3.45 (2H, m, CH 2 ), 5.06 (2H, s, OCH 2 Ph), 6.79 (1H, dd, J 1 = 5.12 Hz, J 2 = 7.96 Hz, Py), 7.04 (1H, dd, J 1 = 1.32 Hz, J 2 = 7.96 Hz, Py), 7.26-7.28 (1H, m, Ph), 7.33-7.36 (4H, m, Ph + NH), 7.78 (1H, dd, J 1 = 1.32 Hz, J 2 = 5.12 Hz, Py), 9.40 (1H, s, NH)
화합물 71: 1-(3-(3-Compound 71: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.44 (9H, s, 3CH3), 5.06 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.01 (1H, dd, J1 = 1.32 Hz, J2 = 8.0 Hz, Py), 7.19 (1H, s, NH), 7.27-7.36 (4H, m, Ph), 7.76 (1H, dd, J1 = 1.32 Hz, J2 = 5.12 Hz, Py), 9.44 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.44 (9H, s, 3CH 3 ), 5.06 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz , Py), 7.01 (1H, dd, J 1 = 1.32 Hz, J 2 = 8.0 Hz, Py), 7.19 (1H, s, NH), 7.27-7.36 (4H, m, Ph), 7.76 (1H, dd) , J 1 = 1.32 Hz, J 2 = 5.12 Hz, Py), 9.44 (1H, s, NH)
화합물 72: 1-(3-(4-Compound 72: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.58-1.67 (10H, m, Cycloheptyl), 1.97-1.98 (2H, m, Cycloheptyl), 4.00-4.04 (1H, m, Cycloheptyl), 5.06 (2H, s, OCH2Ph), 6.81 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.03 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.31 (3H, d, J = 8.4 Hz, Ph+NH), 7.37 (2H, d, J = 8.4 Hz, Ph), 7.77 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 9.52 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.58-1.67 (10H, m, Cycloheptyl), 1.97-1.98 (2H, m, Cycloheptyl), 4.00-4.04 (1H, m, Cycloheptyl), 5.06 (2H, s , OCH 2 Ph), 6.81 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.03 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.31 ( 3H, d, J = 8.4 Hz, Ph + NH), 7.37 (2H, d, J = 8.4 Hz, Ph), 7.77 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 9.52 (1H, s, NH)
화합물 73: 1-(3-(4-Compound 73: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2,4,4-) Pyridin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.02 (9H, s, 3CH3), 1.45 (6H, s, 2CH3), 1.81 (2H, CH2), 5.05 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.02 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.17 (1H, s, NH), 7.31 (2H, d, J = 8.4 Hz, Ph), 7.37 (2H, d, J = 8.4 Hz, Ph), 7.74 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 9.49 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.02 (9H, s, 3CH 3 ), 1.45 (6H, s, 2CH 3 ), 1.81 (2H, CH 2 ), 5.05 (2H, s, OCH 2 Ph) , 6.77 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.02 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.17 (1H, s, NH ), 7.31 (2H, d, J = 8.4 Hz, Ph), 7.37 (2H, d, J = 8.4 Hz, Ph), 7.74 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py) , 9.49 (1H, s, NH)
화합물 74: 1-(3-(4-Compound 74: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 1.10 (3H, t, J = 7.2 Hz, CH3), 3.22-3.29 (2H, m, Ph), 5.21 (2H, s, OCH2Ph), 6.93 (1H, dd, J1 = 8.1 Hz, J2 = 5.1 Hz, Py), 7.43 (1H, d, J = 8.1 Hz, Py), 7.47 (2H, d, J = 8.4 Hz, Ph), 7.54 (2H, d, J = 8.4 Hz, Ph), 7.69 (1H, s, NH), 7.79 (1H, d, J = 5.1 Hz, Py), 9.21 (1H, s, NH)
1 H NMR (300 MHz, DMSO -d 6) δ = 1.10 (3H, t, J = 7.2 Hz, CH 3), 3.22-3.29 (2H, m, Ph), 5.21 (2H, s, OCH 2 Ph) , 6.93 (1H, dd, J 1 = 8.1 Hz, J 2 = 5.1 Hz, Py), 7.43 (1H, d, J = 8.1 Hz, Py), 7.47 (1H, s, NH), 7.79 (1H, d, J = 5.1 Hz, Py)
화합물 75: 1-(3-(4-Compound 75: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.57 (9H, s, 3CH3), 5.10 (2H, s, OCH2Ph), 6.77 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.12 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.33 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, d, J = 8.4 Hz, Ph), 7.50 (1H, s, NH), 7.87 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 11.97 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.57 (9H, s, 3CH 3 ), 5.10 (2H, s, OCH 2 Ph), 6.77 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz , Py), 7.12 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.33 (2H, d, J = 8.4 Hz, Ph), 7.40 (2H, d, J = 8.4 Hz, Ph), 7.50 (1H, s, NH), 7.87 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 11.97 (1H, s, NH)
실시예Example 3.1. 1-(3-(3- 3.1. 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
3-(3-플루오르벤질옥시)피리딘-2-아민 (220 mg, 1.01 mmol)과 2-클로로에틸 아이소시아네이트 (0.1 mL, 1.21 mmol), DIPEA (0.53 mL, 3.02 mmol)를 테트라하이드로퓨란(0.25 M)에 녹인 후 15시간 동안 가열 환류 시켰다. 반응 종결 후, 용매를 감압 농축하고, 잔여물을 컬럼크로마토그래피법 (초산에틸/노르말헥산 =1/2)으로 분리 정제하여 72.92%의 수율로 목적 화합물 238 mg을 얻었다.3- (3-fluorobenzyloxy) pyridin-2-amine (220 mg, 1.01 mmol), 2-chloroethyl isocyanate (0.1 mL, 1.21 mmol) and DIPEA (0.53 mL, 3.02 mmol) were added to tetrahydrofuran (0.25 It was dissolved in M) and heated to reflux for 15 hours. After the completion of the reaction, the solvent was concentrated under reduced pressure, and the residue was purified by column chromatography (ethyl acetate / normal hexane = 1/2) to obtain 238 mg of the target compound in a yield of 72.92%.
1H NMR (400 MHz, CDCl3) δ = 3.69-6.76 (4H, m, 2CH2), 5.11 (2H, OCH2Ph), 6.83 (1H, dd, J1 = 5.11 Hz, J2 = 7.96 Hz, Py), 7.05-7.09 (3H, m, Py+Ph), 7.16 (1H, d, J = 7.56 Hz, Ph), 7.35-7.41 (6H, m, Ph+NH), 7.81 (1H, dd, J1 = 1.30 Hz, J2 = 5.11 Hz, Py), 9.90 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.69-6.76 (4H, m, 2CH 2 ), 5.11 (2H, OCH 2 Ph), 6.83 (1H, dd, J 1 = 5.11 Hz, J 2 = 7.96 Hz , Py), 7.05-7.09 (3H, m, Py + Ph), 7.16 (1H, d, J = 7.56 Hz, Ph), 7.35-7.41 (6H, m, Ph + NH), 7.81 (1H, dd, J 1 = 1.30 Hz, J 2 = 5.11 Hz, Py), 9.90 (1H, s, NH)
실시예Example 3.2. 1-(3-(3- 3.2. 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-(피페라진-1-일)에틸) Pyridin-2-yl) -3- (2- (piperazin-1-yl) ethyl) 유레아Urea
탄산칼륨 (128.07 mg, 0.93 mmol)과 피페라진 (53.21 mg, 0.62 mmol)을 아세토니트릴 (5 mL)에 녹인 후, 1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아 (100 mg, 0.31 mmol)를 천천히 적가한 후 20 시간 동안 가열 환류시킨다. 반응물을 실온까지 식힌 후, 물을 넣은 후, 혼합용액을 초산에틸로 추출하여 황산나트륨으로 건조시키고, 감압 여과하여 감압 증류시킨다. 잔여물을 컬럼크로마토그래피법 (메틸렌클로라이드/메탄올 =1/1)으로 분리 정제하여 16.99%의 수율로 목적화합물 19.6 mg 얻었다.Potassium carbonate (128.07 mg, 0.93 mmol) and piperazine (53.21 mg, 0.62 mmol) were dissolved in acetonitrile (5 mL) and then 1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3 -(2-chloroethyl) urea (100 mg, 0.31 mmol) is slowly added dropwise and heated to reflux for 20 hours. After the reaction was cooled to room temperature, water was added, the mixture was extracted with ethyl acetate, dried over sodium sulfate, filtered under reduced pressure and distilled under reduced pressure. The residue was separated and purified by column chromatography (methylene chloride / methanol = 1/1) to give 19.6 mg of the target compound in a yield of 16.99%.
1H NMR (400 MHz, CDCl3) δ = 2.49 (4H, brs, piperazine), 2.58 (2H, t, J = 6.4 Hz, CH2), 2.91-2.93 (4H, m, piperazine), 3.49-3.53 (2H, m, CH2), 5.09 (2H, s, OCH2Ph), 6.81 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.03-7.09 (3H, m, Ph+Py), 7.16 (1H, d, J = 7.64 Hz, Ph), 7.34-7.40 (2H, m, Ph+NH), 7.81 (1H, dd, J1 = 1.04 Hz, J2 = 5.2 Hz, Py),9.73 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.49 (4H, brs, piperazine), 2.58 (2H, t, J = 6.4 Hz, CH 2 ), 2.91-2.93 (4H, m, piperazine), 3.49-3.53 (2H, m, CH 2 ), 5.09 (2H, s, OCH 2 Ph), 6.81 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.03-7.09 (3H, m, Ph + Py), 7.16 (1H, d, J = 7.64 Hz, Ph), 7.34-7.40 (2H, m, Ph + NH), 7.81 (1H, dd, J 1 = 1.04 Hz, J 2 = 5.2 Hz, Py ), 9.73 (1H, s, NH)
이하, 하기 화합물 76 내지 89를 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
Hereinafter, the following Compounds 76 to 89 were obtained by a method similar to the above Example, and the analysis results of these compounds were as follows:
화합물 76: 1-(3-(Compound 76: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.69-6.74 (4H, m, 2CH2), 5.10 (2H, OCH2Ph), 6.83 (1H, dd, J1 = 5.10 Hz, J2 = 8.02 Hz, Py), 7.10 (1H, dd, J1 = 1.25 Hz, J2 = 8.02 Hz, Py), 7.36-7.44 (6H, m, Ph+NH), 7.79 (1H, dd, J1 = 1.25 Hz, J2 = 5.10 Hz, Py), 9.91 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.69-6.74 (4H, m, 2CH 2 ), 5.10 (2H, OCH 2 Ph), 6.83 (1H, dd, J 1 = 5.10 Hz, J 2 = 8.02 Hz , Py), 7.10 (1H, dd, J 1 = 1.25 Hz, J 2 = 8.02 Hz, Py), 7.36-7.44 (6H, m, Ph + NH), 7.79 (1H, dd, J 1 = 1.25 Hz, J 2 = 5.10 Hz, Py), 9.91 (1H, s, NH)
화합물 77: 1-(3-(Compound 77: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(2-(4-Pyridin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) 유레아-1-yl) ethyl) urea
1H NMR (400 MHz, CDCl3) δ = 2.34 (3H, s, CH3), 2.58-2.63 (10H, m, 5CH2), 3.48-3.53 (2H, m, CH2), 5.09 (2H, s, OCH2Ph), 6.82 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.09 (1H, d, J = 8.0 Hz, Py), 7.35-7.40 (5H, m, Ph), 7.42 (1H, s, NH), 7.78 (1H, d, J = 5.2 Hz, Ph), 9.72 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.34 (3H, s, CH 3 ), 2.58-2.63 (10H, m, 5CH 2 ), 3.48-3.53 (2H, m, CH 2 ), 5.09 (2H, s, OCH 2 Ph), 6.82 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.09 (1H, d, J = 8.0 Hz, Py), 7.35-7.40 (5H, m, Ph), 7.42 (1H, s, NH), 7.78 (1H, d, J = 5.2 Hz, Ph), 9.72 (1H, s, NH)
화합물 78: 1-(3-(Compound 78: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(2-(피페라진-1일)에틸) Pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.58-2.66 (H, m, piperazine), 2.76 (2H, m, CH2), 3.14-3.15 (2H, m, piperazine), 3.48-3.53 (2H, m, CH2), 5.09 (2H, s, OCH2Ph), 679-6.84 (1H, m, Py), 7.09 (1H, t, J = 8.0 Hz, Py), 7.39 (5H, m, Ph), 7.77 (1H, dd, J1 = 4.0 Hz, J2 = 12.0 Hz, Py), 9.74 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.58-2.66 (H, m, piperazine), 2.76 (2H, m, CH 2 ), 3.14-3.15 (2H, m, piperazine), 3.48-3.53 (2H, m, CH 2 ), 5.09 (2H, s, OCH 2 Ph), 679-6.84 (1H, m, Py), 7.09 (1H, t, J = 8.0 Hz, Py), 7.39 (5H, m, Ph) , 7.77 (1H, doublet of doublets, J 1 = 4.0 Hz, J 2 = 12.0 Hz, Py), 9.74 (1H, s, NH)
화합물 79: 1-(3-(3-Compound 79: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.69-6.76 (4H, m, 2CH2), 5.11 (2H, OCH2Ph), 6.83 (1H, dd, J1 = 5.11 Hz, J2 = 7.96 Hz, Py), 7.05-7.09 (3H, m, Py+Ph), 7.16 (1H, d, J = 7.56 Hz, Ph), 7.35-7.41 (6H, m, Ph+NH), 7.81 (1H, dd, J1 = 1.30 Hz, J2 = 5.11 Hz, Py), 9.90 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.69-6.76 (4H, m, 2CH 2 ), 5.11 (2H, OCH 2 Ph), 6.83 (1H, dd, J 1 = 5.11 Hz, J 2 = 7.96 Hz , Py), 7.05-7.09 (3H, m, Py + Ph), 7.16 (1H, d, J = 7.56 Hz, Ph), 7.35-7.41 (6H, m, Ph + NH), 7.81 (1H, dd, J 1 = 1.30 Hz, J 2 = 5.11 Hz, Py), 9.90 (1H, s, NH)
화합물 80: 1-(3-(3-Compound 80: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-(4-Pyridin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) -1-yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.26 (2H, t, J = 7.12 Hz, CH2), 2.31 (3H, s, CH3), 2.42-2.59 (8H, m, piperazine), 2.61 (2H, t, J = 6.4 Hz, CH2), 5.09 (2H, s, OCH2Ph), 6.81 (1H, dd, J1 = 5.06 Hz, J2 = 7.96 Hz, Py), 7.03-7.08 (3H, m, Ph+Py), 7.16 (1H, d, J = 7.8 Hz, Ph), 7.37-7.39 (2H, m, Ph), 7.80 (1H, dd, J1 = 1.28 Hz, J2 = 5.06 Hz, Py), 8.76 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.26 (2H, t, J = 7.12 Hz, CH 2 ), 2.31 (3H, s, CH 3 ), 2.42-2.59 (8H, m, piperazine), 2.61 ( 2H, t, J = 6.4 Hz, CH 2 ), 5.09 (2H, s, OCH 2 Ph), 6.81 (1H, dd, J 1 = 5.06 Hz, J 2 = 7.96 Hz, Py), 7.03-7.08 (3H , m, Ph + Py), 7.16 (1H, d, J = 7.8 Hz, Ph), 7.37-7.39 (2H, m, Ph), 7.80 (1H, dd, J 1 = 1.28 Hz, J 2 = 5.06 Hz , Py), 8.76 (1H, s, NH)
화합물 81: 1-(3-(3-Compound 81: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-(피페라진-1일)에틸) Pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.49 (4H, brs, piperazine), 2.58 (2H, t, J = 6.4 Hz, CH2), 2.91-2.93 (4H, m, piperazine), 3.49-3.53 (2H, m, CH2), 5.09 (2H, s, OCH2Ph), 6.81 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.03-7.09 (3H, m, Ph+Py), 7.16 (1H, d, J = 7.64 Hz, Ph), 7.34-7.40 (2H, m, Ph+NH), 7.81 (1H, dd, J1 = 1.04 Hz, J2 = 5.2 Hz, Py), 9.73 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.49 (4H, brs, piperazine), 2.58 (2H, t, J = 6.4 Hz, CH 2 ), 2.91-2.93 (4H, m, piperazine), 3.49-3.53 (2H, m, CH 2 ), 5.09 (2H, s, OCH 2 Ph), 6.81 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.03-7.09 (3H, m, Ph + Py), 7.16 (1H, d, J = 7.64 Hz, Ph), 7.34-7.40 (2H, m, Ph + NH), 7.81 (1H, dd, J 1 = 1.04 Hz, J 2 = 5.2 Hz, Py ), 9.73 (1H, s, NH)
화합물 82: 1-(3-(4-Compound 82: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.63-3.73 (4H, m, 2CH2), 5.05 (2H, s, OCH2Ph), 6.83 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.07-7.12 (3H, m, Ph+Py), 7.35-7.39 (3H, m, Ph+NH), 7.80 (1H, d, J = 5.2 Hz, Py), 9.90 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.63-3.73 (4H, m, 2CH 2 ), 5.05 (2H, s, OCH 2 Ph), 6.83 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.07-7.12 (3H, m, Ph + Py), 7.35-7.39 (3H, m, Ph + NH), 7.80 (1H, d, J = 5.2 Hz, Py), 9.90 (1H, s, NH)
화합물 83: 1-(3-(2-Compound 83: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.69-6.76 (4H, m, 2CH2), 5.20 (2H, OCH2Ph), 6.83 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.06 (1H, dd, J1 = 1.32 Hz, J2 = 8.0 Hz, Py), 7.30-7.34 (2H, m, Ph) 7.41-7.45 (3H, m, Ph+NH), 7.81 (1H, dd, J1 = 1.32 Hz, J2 = 5.12 Hz, Py), 9.91 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.69-6.76 (4H, m, 2CH 2 ), 5.20 (2H, OCH 2 Ph), 6.83 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz , Py), 7.06 (1H, dd, J 1 = 1.32 Hz, J 2 = 8.0 Hz, Py), 7.30-7.34 (2H, m, Ph) 7.41-7.45 (3H, m, Ph + NH), 7.81 ( 1H, dd, J 1 = 1.32 Hz, J 2 = 5.12 Hz, Py), 9.91 (1H, s, NH)
화합물 84: 1-(3-(2-Compound 84: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-(4-Pyridin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) -1-yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.30 (3H, s, CH3), 2.37-2.62 (10H, m, 5CH2), 3.49-3.57 (2H, m, CH2), 5.20 (2H, s, OCH2Ph), 6.83 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 6.83 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.09 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.30-7.34 (2H, m, Ph), 7.39 (1H, s, NH), 7.41-7.44 (2H, m, Ph), 7.81 (1H, dd, J1 = 5.12 Hz, J2 = 1.2 Hz, Py), 9.72 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.30 (3H, s, CH 3 ), 2.37-2.62 (10H, m, 5CH 2 ), 3.49-3.57 (2H, m, CH 2 ), 5.20 (2H, s, OCH 2 Ph), 6.83 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz, Py), 6.83 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz, Py), 7.09 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.30-7.34 (2H, m, Ph), 7.39 (1H, s, NH), 7.41-7.44 (2H, m, Ph) , 7.81 (1H, doublet of doublets, J 1 = 5.12 Hz, J 2 = 1.2 Hz, Py), 9.72 (1H, s, NH)
화합물 85: 1-(3-(2-Compound 85: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아Pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) urea
1H NMR (400 MHz, CDCl3) δ = 2.50 (4H, brs, 2CH2), 2.58 (2H, t, J = 6.4 Hz, CH2), 2.39 (4H, t, J = 4.8 Hz, 2CH2), 3.49-3.53 (2H, m, CH2), 5.20 (2H, s, OCH2Ph), 6.83 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.09 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.28-7.34 (2H, m, Ph), 7.39 (1H, s, NH), 7.41-7.44 (2H, m, Ph), 7.81 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 9.74 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.50 (4H, brs, 2CH 2 ), 2.58 (2H, t, J = 6.4 Hz, CH 2 ), 2.39 (4H, t, J = 4.8 Hz, 2CH 2 ), 3.49-3.53 (2H, m, CH 2 ), 5.20 (2H, s, OCH 2 Ph), 6.83 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.09 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.28-7.34 (2H, m, Ph), 7.39 (1H, s, NH), 7.41-7.44 (2H, m, Ph), 7.81 ( 1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 9.74 (1H, s, NH)
화합물 86: 1-(3-(3-Compound 86: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.69-6.74 (4H, m, 2CH2), 5.07 (2H, OCH2Ph), 6.83 (1H, dd, J1 = 5.12 Hz, J2 = 8.0 Hz, Py), 7.06 (1H, dd, J1 = 1.28 Hz, J2 = 8.0 Hz, Py), 7.27-7.36 (4H, m, Ph) 7.41 (1H, s, NH), 7.81 (1H, dd, J1 = 1.28 Hz, J2 = 5.12 Hz, Py), 9.90 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.69-6.74 (4H, m, 2CH 2 ), 5.07 (2H, OCH 2 Ph), 6.83 (1H, dd, J 1 = 5.12 Hz, J 2 = 8.0 Hz , Py), 7.06 (1H, dd, J 1 = 1.28 Hz, J 2 = 8.0 Hz, Py), 7.27-7.36 (4H, m, Ph) 7.41 (1H, s, NH), 7.81 (1H, dd, J 1 = 1.28 Hz, J 2 = 5.12 Hz, Py), 9.90 (1H, s, NH)
화합물 87: 1-(3-(3-Compound 87: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-(4-Pyridin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) -1-yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.31 (3H, s, CH3), 2.44-2.62 (10H, m, piperazine+CH2), 3.49-3.53 (2H, m, CH2), 5.06 (2H, s, OCH2Ph), 6.81 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 7.04 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 7.26-7.28 (1H, m, Ph), 7.33-7.36 (4H, m, Ph+NH), 7.80 (1H, dd, J1 = 1.2 Hz, J2 = 5.2 Hz, Py), 9.69 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.31 (3H, s, CH 3 ), 2.44-2.62 (10H, m, piperazine + CH 2 ), 3.49-3.53 (2H, m, CH 2 ), 5.06 ( 2H, s, OCH 2 Ph), 6.81 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 7.04 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py) , 7.26-7.28 (1H, m, Ph), 7.33-7.36 (4H, m, Ph + NH), 7.80 (1H, dd, J 1 = 1.2 Hz, J 2 = 5.2 Hz, Py), 9.69 (1H, s, NH)
화합물 88: 1-(3-(3-Compound 88: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아Pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) urea
1H NMR (400 MHz, CDCl3) δ = 2.52 (4H, brs, 2CH2), 2.58 (2H, t, J = 6.4 Hz, CH2), 2.94 (4H, t, J = 4.8 Hz, 2CH2), 3.49-3.53 (2H, m, CH2), 6.81 (1H, dd, J1 = 4.8 Hz, J2 = 8.0 Hz, Py), 7.04 (1H, dd, J1 = 1.2 Hz, J2 = 8.0 Hz, Py), 7.27-7.28 (1H, m, Ph), 7.33-7.37 (4H, m, Ph+NH), 7.81 (1H, dd, J1 = 1.2 Hz, J2 = 4.8 Hz, Py), 9.72 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.52 (4H, brs, 2CH 2 ), 2.58 (2H, t, J = 6.4 Hz, CH 2 ), 2.94 (4H, t, J = 4.8 Hz, 2CH 2 ), 3.49-3.53 (2H, m, CH 2 ), 6.81 (1H, dd, J 1 = 4.8 Hz, J 2 = 8.0 Hz, Py), 7.04 (1H, dd, J 1 = 1.2 Hz, J 2 = 8.0 Hz, Py), 7.27-7.28 (1H, m, Ph), 7.33-7.37 (4H, m, Ph + NH), 7.81 (1H, dd, J 1 = 1.2 Hz, J 2 = 4.8 Hz, Py) , 9.72 (1H, s, NH)
화합물 89: 1-(3-(4-Compound 89: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(2-Pyridin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.69-3.74 (4H, m, 2CH2), 5.07 (2H, s, OCH2Ph), 6.83 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.07 (1H, d, J = 8.0 Hz, Py), 7.32 (2H, d, J = 8.4 Hz, Ph), 7.38 (3H, d, J = 8.4 Hz, Ph+NH), 7.80 (1H, d, J = 4.8 Hz, Py), 9.89 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.69-3.74 (4H, m, 2CH 2 ), 5.07 (2H, s, OCH 2 Ph), 6.83 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.07 (1H, d, J = 8.0 Hz, Py), 7.32 (2H, d, J = 8.4 Hz, Ph), 7.38 (3H, d, J = 8.4 Hz, Ph + NH), 7.80 (1H, d, J = 4.8 Hz, Py), 9.89 (1H, s, NH)
실시예Example 4. 1. 3-( 4. 1. 3- ( 벤질옥시Benzyloxy )피라진-2-아민Pyrazine-2-amine
수소화나트륨 (188.6 mg, 4.72 mmol)을 N,N-디메틸포름아마이드 (3 mL)에 녹인 후 벤질 알콜을 천천히 적가하고 실온에서 1 시간 동안 교반한다. 혼합용액에 2-아미노-3-클로로 피라진을 천천히 적가하고 100℃에서 15시간 동안 가열 환류 시킨다. 반응물을 실온까지 식힌 후 용매를 감압 증류하고 초산에틸로 추출한다. 유기층을 황산나트륨으로 건조시킨 후, 감압 필터하여 감압 농축한다. 잔여물을 컬럼크로마토그래피법 (초산에틸/노르말헥산 =1/4)으로 분리 정제하여 53.76%의 수율로 목적 화합물 300 mg 얻었다.Sodium hydride (188.6 mg, 4.72 mmol) is dissolved in N, N-dimethylformamide (3 mL), and benzyl alcohol is slowly added dropwise and stirred at room temperature for 1 hour. 2-amino-3-chloropyrazine was slowly added dropwise to the mixed solution and heated to reflux at 100 ° C. for 15 hours. After the reaction was cooled to room temperature, the solvent was distilled under reduced pressure and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, and then concentrated under reduced pressure by filtration under reduced pressure. The residue was separated and purified by column chromatography (ethyl acetate / n-hexane = 1/4) to obtain 300 mg of the title compound in 53.76% yield.
1H NMR (400 MHz, CDCl3) δ = 5.29 (2H, brs, NH2), 5.41 (2H, s, OCH2Ph), 7.36-7.46 (4H, m, Ph), 7.51 (1H, d, J = 3.2 Hz, Ph), 7.71 (1H, d, J = 2.8 Hz, pyrazine), 7.93 (1H, d, J = 2.8 Hz, pyrazine)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.29 (2H, brs, NH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.36-7.46 (4H, m, Ph), 7.51 (1H, d, J = 3.2 Hz, Ph), 7.71 (1H, d, J = 2.8 Hz, pyrazine), 7.93 (1H, d, J = 2.8 Hz, pyrazine)
실시예Example 4.2. 1-(3-( 4.2. 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
3-(벤질옥시)피라진-2-아민 (100 mg, 0.5 mmol)과 2-플루오르 아이소시아네이트 (0.67 mL, 0.60 mmol)을 테트라하이드로퓨란 (0.25 M)에 녹인 후 8 시간 동안 가열 환류시킨다. 반응 종결 후, 용매를 감압 농축한다. 잔여물을 메탄올로 씻어주고 감압 필터하여 69.43%의 수율로 목적화합물 122.6 mg을 얻었다.3- (benzyloxy) pyrazin-2-amine (100 mg, 0.5 mmol) and 2-fluoro isocyanate (0.67 mL, 0.60 mmol) are dissolved in tetrahydrofuran (0.25 M) and heated to reflux for 8 hours. After completion of the reaction, the solvent is concentrated under reduced pressure. The residue was washed with methanol and filtered under reduced pressure to obtain 122.6 mg of the target compound in a yield of 69.43%.
1H NMR (400 MHz, CDCl3) δ = 5.38 (2H, s, OCH2Ph), 6.96-7.09 (3H, m, Ph), 7.32-7.40 (5H, m, Ph), 7.43 (1H, s, NH), 7.67 (1H, d, J = 3.08 Hz, pyrazine), 7.72 (1H, d, J = 3.08 Hz, pyrazine), 8.21-8.23 (1H, m, Ph), 11.56 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.38 (2H, s, OCH 2 Ph), 6.96-7.09 (3H, m, Ph), 7.32-7.40 (5H, m, Ph), 7.43 (1H, s , NH), 7.67 (1H, d, J = 3.08 Hz, pyrazine), 7.72 (1H, d, J = 3.08 Hz, pyrazine), 8.21-8.23 (1H, m, Ph), 11.56 (1H, s, NH )
이하, 하기 화합물 90 내지 133을 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
Hereinafter, the following Compounds 90 to 133 were obtained by a method similar to the above Examples, and the analysis results of these compounds were as follows:
화합물 90: 1-(3-(Compound 90: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.38 (2H, s, OCH2Ph), 6.96-7.09 (3H, m, Ph), 7.32-7.40 (5H, m, Ph), 7.43 (1H, s, NH), 7.67 (1H, d, J = 3.08 Hz, pyrazine), 7.72 (1H, d, J = 3.08 Hz, pyrazine), 8.21-8.23 (1H, m, Ph), 11.56 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.38 (2H, s, OCH 2 Ph), 6.96-7.09 (3H, m, Ph), 7.32-7.40 (5H, m, Ph), 7.43 (1H, s , NH), 7.67 (1H, d, J = 3.08 Hz, pyrazine), 7.72 (1H, d, J = 3.08 Hz, pyrazine), 8.21-8.23 (1H, m, Ph), 11.56 (1H, s, NH )
화합물 91: 1-(3-(Compound 91: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.47 (2H, s, OCH2Ph), 6.86-6.88 (1H, m, Ph), 7.26-7.29 (1H, m, Ph), 7.32-7.41 (4H, m, Ph), 7.53-7.60 (3H, m, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.93 (1H, d, J = 3.0 Hz, pyrazine), 8.21-8.23 (1H, m, Ph), 9.00 (1H, s, NH), 11.01 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.47 (2H, s, OCH 2 Ph), 6.86-6.88 (1H, m, Ph), 7.26-7.29 (1H, m, Ph), 7.32-7.41 (4H, m, Ph), 7.53-7.60 (3H, m, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.93 (1H, d, J = 3.0 Hz, pyrazine), 8.21-8.23 (1H, m, Ph), 9.00 (1H, s, NH), 11.01 (1H, s, NH)
화합물 92: 1-(3-(Compound 92: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(3,4-Pyrazin-2-yl) -3- (3,4- 다이틀로로페닐Dietrolophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.38 (2H, s, OCH2Ph), 7.29-7.39 (7H, m, Ph), 7.41 (1H, s, NH), 7.68-7.71 (3H, m, Ph+pyrazine), 11.35 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.38 (2H, s, OCH 2 Ph), 7.29-7.39 (7H, m, Ph), 7.41 (1H, s, NH), 7.68-7.71 (3H, m , Ph + pyrazine), 11.35 (1H, s, NH)
화합물 93: 1-(3-(Compound 93: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-벤질 Pyrazin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 4.60 (2H, d, J = 5.84 Hz, OCH2Ph), 5.41 (2H, s, OCH2Ph), 6.96-7.09 (3H, m, Ph), 7.31-7.44 (10H, m, 2Ph), 7.62-7.64 (2H, m, pyrazine), 9.44(1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.60 (2H, d, J = 5.84 Hz, OCH 2 Ph), 5.41 (2H, s, OCH 2 Ph), 6.96-7.09 (3H, m, Ph), 7.31-7.44 (10H, m, 2Ph), 7.62-7.64 (2H, m, pyrazine), 9.44 (1H, s, NH)
화합물 94: 1-(3-(Compound 94: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.45 (2H, s, OCH2Ph), 7.10 (1H, t, J = 7.40 Hz, Ph), 7.32-7.48 (6H, m, Ph+pyrazine), 7.58 (2H, d, J = 7.58 Hz, Ph), 7.72 (1H, m, Ph), 7.75 (1H, s, NH), 11.2 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.45 (2H, s, OCH 2 Ph), 7.10 (1H, t, J = 7.40 Hz, Ph), 7.32-7.48 (6H, m, Ph + pyrazine), 7.58 (2H, d, J = 7.58 Hz, Ph), 7.72 (1H, m, Ph), 7.75 (1H, s, NH), 11.2 (1H, s, NH)
화합물 95: 1-(3-(Compound 95: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.38 (2H, s, OCH2Ph), 6.98-7.01 (1H, m, Ph), 7.18 (2H, t, J = 8.04 Hz, Ph), 7.32-7.40 (7H, m, Ph+NH), 7.58 (1H, t, J = 2.01 Hz, Ph), 7.67 (1H, d, J = 3.12 Hz, pyrazine), 7.69 (1H, d, J = 3.12 Hz, pyrazine), 11.31 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.38 (2H, s, OCH 2 Ph), 6.98-7.01 (1H, m, Ph), 7.18 (2H, t, J = 8.04 Hz, Ph), 7.32- 7.40 (7H, m, Ph + NH), 7.58 (1H, t, J = 2.01 Hz, Ph), 7.67 (1H, d, J = 3.12 Hz, pyrazine), 7.69 (1H, d, J = 3.12 Hz, pyrazine), 11.31 (1H, s, NH)
화합물 96: 1-(3-(Compound 96: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.44 (2H, s, OCH2Ph), 7.14 (2H, d, J = 8.21 Hz, Ph), 7.38-7.46 (7H, m, Ph), 7.71 (1H, d, J = 3.14 Hz, pyrazine), 7.75 (1H, d, J = 3.14 Hz, pyrazine), 11.17 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.44 (2H, s, OCH 2 Ph), 7.14 (2H, d, J = 8.21 Hz, Ph), 7.38-7.46 (7H, m, Ph), 7.71 (1H, d, J = 3.14 Hz, pyrazine), 7.75 (1H, d, J = 3.14 Hz, pyrazine), 11.17 (1H, s, NH)
화합물 97: 1-(3-(Compound 97: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(나프탈렌-1-일) Pyrazin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.51 (2H, s, OCH2Ph), 7.34-7.42 (3H, m, Ph), 7.52 (1H, t, J = 7.93 Hz, Ph), 7.57-7.60 (3H, m, Ph), 7.64-7.73 (2H, m, Ph), 7.86 (1H, d, J = 3.04 Hz, pyrazine), 7.97 (1H, d, J = 8.08 Hz, Ph), 8.05 (1H, d, J = 3.04 Hz, pyrazine), 8.13 (2H, t, J = 6.98 Hz, Ph), 9.14 (1H, s, NH), 11.62 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.51 (2H, s, OCH 2 Ph), 7.34-7.42 (3H, m, Ph), 7.52 (1H, t, J = 7.93 Hz, Ph), 7.57-7.60 (3H, m, Ph), 7.64-7.73 (2H, m, Ph), 7.86 (1H, d, J = 3.04 Hz, pyrazine), 7.97 (1H, d, J = 8.08 Hz, Ph), 8.05 (1H, d, J = 3.04 Hz, pyrazine), 8.13 (2H, t, J = 6.98 Hz, Ph), 9.14 (1H, s, NH), 11.62 (1H, s, NH)
화합물 98: 1-(3-(3-Compound 98: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) 유레아) Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.49 (2H, s, OCH2Ph), 7.08-7.11 (1H, m, Ph), 7.17-7.21 (2H, m, Ph), 7.27-7.32 (1H, m, Ph), 7.37-7.45 (2H, m, Ph), 7.50 (1H, d, J = 9.86 Hz, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.91 (1H, d, J = 3.0 Hz, pyrazine), 8.19-8.23 (1H, m, Ph), 9.34 (1H, s, NH), 11.32 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.49 (2H, s, OCH 2 Ph), 7.08-7.11 (1H, m, Ph), 7.17-7.21 (2H, m, Ph), 7.27-7.32 (1H, m, Ph), 7.37-7.45 (2H, m, Ph), 7.50 (1H, d, J = 9.86 Hz, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.91 (1H , d, J = 3.0 Hz, pyrazine), 8.19-8.23 (1H, m, Ph), 9.34 (1H, s, NH), 11.32 (1H, s, NH)
화합물 99: 1-(3-(3-Compound 99: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) 유레아) Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.48 (2H, s, OCH2Ph), 6.87-6.90 (1H, m, Ph), 7.14-7.16 (1H, m, Ph), 7.28-7.49 (5H, m, Ph), 7.59 (1H, d, J = 11.92 Hz, Ph), 7.84 (1H, d, J = 2.99 Hz, pyrazine), 7.95 (1H, d, J = 2.99 Hz, pyrazine), 9.18 (1H, s, NH), 11.08 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.48 (2H, s, OCH 2 Ph), 6.87-6.90 (1H, m, Ph), 7.14-7.16 (1H, m, Ph), 7.28-7.49 (5H, m, Ph), 7.59 (1H, d, J = 11.92 Hz, Ph), 7.84 (1H, d, J = 2.99 Hz, pyrazine), 7.95 (1H, d, J = 2.99 Hz, pyrazine), 9.18 (1H, s, NH), 11.08 (1H, s, NH)
화합물 100: 1-(3-(3-Compound 100: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(3,4-Pyrazin-2-yl) -3- (3,4- 다이틀로로페Daitlope 닐) Neil) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.45 (2H, s, OCH2Ph), 7.06-7.08 (1H, m, Ph), 7.13-7.16 (1H, m, Ph), 7.22 (1H, d, J = 7.60 Hz, Ph), 7.35-7.39 (2H, m, Ph), 7.43-7.46 (1H, m, Ph), 7.47 (1H, s, NH), 7.75 (1H, m, pyrazine), 7.77-7.78 (2H, m, Ph+pyrazine), 11.40 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.45 (2H, s, OCH 2 Ph), 7.06-7.08 (1H, m, Ph), 7.13-7.16 (1H, m, Ph), 7.22 (1H, d , J = 7.60 Hz, Ph), 7.35-7.39 (2H, m, Ph), 7.43-7.46 (1H, m, Ph), 7.47 (1H, s, NH), 7.75 (1H, m, pyrazine), 7.77 -7.78 (2H, m, Ph + pyrazine), 11.40 (1H, s, NH)
화합물 101: 1-(3-(3-Compound 101: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-벤질 Pyrazin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 4.47 (2H, d, J = 5.95 Hz, OCH2Ph), 5.45 (2H, s, OCH2Ph), 7.15-7.17 (1H, m, Ph), 7.24-7.26 (1H, m, Ph), 7.32-7.37 (5H, m, Ph), 7.40-7.48 (2H, m, Ph), 7.73 (1H, d, J = 3.0 Hz, pyrazine), 7.80 (1H, d, J = 3.0 Hz, Ph), 8.69 (1H, s, NH), 9.27 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 4.47 (2H, d, J = 5.95 Hz, OCH 2 Ph), 5.45 (2H, s, OCH 2 Ph), 7.15-7.17 (1H, m, Ph ), 7.24-7.26 (1H, m, Ph), 7.32-7.37 (5H, m, Ph), 7.40-7.48 (2H, m, Ph), 7.73 (1H, d, J = 3.0 Hz, pyrazine), 7.80 (1H, d, J = 3.0 Hz, Ph), 8.69 (1H, s, NH), 9.27 (1H, s, NH)
화합물 102: 1-(3-(3-Compound 102: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.49 (2H, s, OCH2Ph), 7.08-7.21 (3H, m, Ph), 7.27-7.32 (1H, m, Ph), 7.37-7.45 (2H, m, Ph), 7.50 (1H, d, J = 9.86 Hz, Ph), 7.83 (1H, d, J = 3.01 Hz, pyrazine), 7.91 (1H, d, J = 3.01 Hz, pyrazine), 8.19-8.23 (1H, t, J = 8.12 Hz, Ph), 9.34 (1H, s, NH), 11.32 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.49 (2H, s, OCH 2 Ph), 7.08-7.21 (3H, m, Ph), 7.27-7.32 (1H, m, Ph), 7.37-7.45 (2H , m, Ph), 7.50 (1H, d, J = 9.86 Hz, Ph), 7.83 (1H, d, J = 3.01 Hz, pyrazine), 7.91 (1H, d, J = 3.01 Hz, pyrazine), 8.19- 8.23 (1H, t, J = 8.12 Hz, Ph), 9.34 (1H, s, NH), 11.32 (1H, s, NH)
화합물 103: 1-(3-(3-Compound 103: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.47 (2H, s, OCH2Ph), 7.09-7.18 (2H, m, Ph), 7.32-7.48 (5H, m, Ph), 7.80 (1H, t, J = 2.0Hz, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.95 (1H, d, J = 3.0 Hz, pyrazine), 9.19 (1H, s, NH), 11.07 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.47 (2H, s, OCH 2 Ph), 7.09-7.18 (2H, m, Ph), 7.32-7.48 (5H, m, Ph), 7.80 (1H , t, J = 2.0 Hz, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.95 (1H, d, J = 3.0 Hz, pyrazine), 9.19 (1H, s, NH), 11.07 ( 1H, s, NH)
화합물 104: 1-(3-(3-Compound 104: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.44 (2H, s, OCH2Ph), 7.06-7.09 (1H, m, Ph), 7.15 (3H, d, J = 8.46 Hz, Ph), 7.22 (1H, d, J = 7.66 Hz, Ph), 7.34-7.38 (1H, m, Ph), 7.43 (1H, s, NH), 7.45 (2H, d, J = 8.38 Hz, Ph), 7.70 (1H, d, J = 3.09 Hz, pyrazine), 7.77 (1H, d, J = 3.09 Hz, pyrazine), 11.15 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.44 (2H, s, OCH 2 Ph), 7.06-7.09 (1H, m, Ph), 7.15 (3H, d, J = 8.46 Hz, Ph), 7.22 (1H, d, J = 7.66 Hz, Ph), 7.34-7.38 (1H, m, Ph), 7.43 (1H, s, NH), 7.45 (2H, d, J = 8.38 Hz, Ph), 7.70 (1H, d, J = 3.09 Hz, pyrazine), 7.77 (1H, d, J = 3.09 Hz, pyrazine), 11.15 (1H, s, NH)
화합물 105: 1-(3-(3-Compound 105: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(나프탈렌-1-일) 유레아Pyrazin-2-yl) -3- (naphthalen-1-yl) urea
1H NMR (400 MHz, DMSO-d6) δ = 5.52 (2H, s, OCH2Ph), 7.16-7.20 (1H, m, Ph), 7.40-7.73 (7H, m, Ph), 7.87 (1H, d, J = 3.0 Hz, pyrazine), 7.95-7.99 (1H, m, Ph), 8.07 (1H, d, J = 3.0 Hz, Ph), 9.31 (1H, s, NH), 11.67 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.52 (2H, s, OCH 2 Ph), 7.16-7.20 (1H, m, Ph), 7.40-7.73 (7H, m, Ph), 7.87 (1H , d, J = 3.0 Hz, pyrazine), 7.95-7.99 (1H, m, Ph), 8.07 (1H, d, J = 3.0 Hz, Ph), 9.31 (1H, s, NH), 11.67 (1H, s , NH)
화합물 106: 1-(3-(4-Compound 106: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) 유레아) Urea
1H NMR (400 MHz, CDCl3) δ = 5.42 (2H, s, OCH2Ph), 7.04-7.14 (5H, m, Ph), 7.42-7.46 (2H, m, Ph), 7.49 (1H, s, NH), 7.73 (1H, d, J = 3.06 Hz, pyrazine), 7.80 (1H, d, J = 3.06 Hz, pyrazine), 8.25-8.30 (1H, m, Ph), 11.61 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.42 (2H, s, OCH 2 Ph), 7.04-7.14 (5H, m, Ph), 7.42-7.46 (2H, m, Ph), 7.49 (1H, s , NH), 7.73 (1H, d, J = 3.06 Hz, pyrazine), 7.80 (1H, d, J = 3.06 Hz, pyrazine), 8.25-8.30 (1H, m, Ph), 11.61 (1H, s, NH )
화합물 107: 1-(3-(4-Compound 107: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) 유레아) Urea
1H NMR (400 MHz, CDCl3) δ = 5.42 (2H, s, OCH2Ph), 6.78-6.80 (1H, m, Ph), 7.09 (2H, t, J = 8.64 Hz, Ph), 7.24-7.28 (1H, m, Ph), 7.42-7.45 (3H, m, Ph+NH), 7.48-7.53 (1H, m, Ph), 7.73 (1H, d, J = 3.11 Hz, pyrazine), 7.77 (1H, d, J = 3.11 Hz, pyrazine), 11.39 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.42 (2H, s, OCH 2 Ph), 6.78-6.80 (1H, m, Ph), 7.09 (2H, t, J = 8.64 Hz, Ph), 7.24- 7.28 (1H, m, Ph), 7.42-7.45 (3H, m, Ph + NH), 7.48-7.53 (1H, m, Ph), 7.73 (1H, d, J = 3.11 Hz, pyrazine), 7.77 (1H , d, J = 3.11 Hz, pyrazine), 11.39 (1H, s, NH)
화합물 108: 1-(3-(4-Compound 108: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(3,4-Pyrazin-2-yl) -3- (3,4- 다이클로로페Dichlorofe 닐) Neil) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.42 (2H, s, OCH2Ph), 7.07-7.11 (2H, m, Ph), 7.37-7.45 (5H, m, Ph), 7.74 (1H, d, J = 3.10 Hz, pyrazine), 7.77 (2H, d, J = 3.10 Hz, pyrazine+NH), 11.41 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.42 (2H, s, OCH 2 Ph), 7.07-7.11 (2H, m, Ph), 7.37-7.45 (5H, m, Ph), 7.74 (1H, d , J = 3.10 Hz, pyrazine), 7.77 (2H, d, J = 3.10 Hz, pyrazine + NH), 11.41 (1H, s, NH)
화합물 109: 1-(3-(4-Compound 109: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.41 (2H, s, OCH2Ph), 7.07-7.11 (2H, m, Ph), 7.14 (2H, d, J = 8.18 Hz, Ph), 7.41-7.45 (5H, m, Ph+NH), 7.70 (1H, d, J = 3.11 Hz, pyrazine), 7.75 (1H, d, J = 3.11 Hz, pyrazine), 11.15 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.41 (2H, s, OCH 2 Ph), 7.07-7.11 (2H, m, Ph), 7.14 (2H, d, J = 8.18 Hz, Ph), 7.41-7.45 (5H, m, Ph + NH), 7.70 (1H, d, J = 3.11 Hz, pyrazine), 7.75 (1H, d, J = 3.11 Hz, pyrazine), 11.15 (1H, s, NH)
화합물 110: 1-(3-(4-Compound 110: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(나프탈렌-1-일) 유레아Pyrazin-2-yl) -3- (naphthalen-1-yl) urea
1H NMR (400 MHz, DMSO-d6) δ = 5.48 (2H, s, OCH2Ph), 7.23 (2H, t, J = 8.86 Hz, Ph), 7.48-7.68 (5H, m, Ph), 7.72 (1H, d, J = 8.12 Hz, Ph), 7.87 (1H, d, J = 3.03 Hz, pyrazine), 7.94-7.98 (1H, m, Ph), 8.05 (1H, d, J = 3.03 Hz, pyrazine), 8.13 (2H, t, J = 8.04 Hz, Ph), 9.18 (1H, s, NH), 11.65 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.48 (2H, s, OCH 2 Ph), 7.23 (2H, t, J = 8.86 Hz, Ph), 7.48-7.68 (5H, m, Ph), 7.72 (1H, d, J = 8.12 Hz, Ph), 7.87 (1H, d, J = 3.03 Hz, pyrazine), 7.94-7.98 (1H, m, Ph), 8.05 (1H, d, J = 3.03 Hz, pyrazine), 8.13 (2H, t, J = 8.04 Hz, Ph), 9.18 (1H, s, NH), 11.65 (1H, s, NH)
화합물 111: 1-(3-(4-Compound 111: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(4-(Pyrazin-2-yl) -3- (4- ( 트리플루오르Trifluorine 메틸)methyl) 페닐Phenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.43 (2H, OCH2Ph), 7.07-7.12 (2H, m, Ph), 7.42-7.46 (2H, m, Ph), 7.50 (1H, s, NH), 7.58 (2H, d, J = 8.60 Hz, Ph), 7.70 (2H, d, J = 8.60 Hz, Ph), 7.75 (1H, d, J = 3.11 Hz, pyrazine), 7.78 (1H, d, J = 3.11 Hz, pyrazine), 11.53 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.43 (2H, OCH 2 Ph), 7.07-7.12 (2H, m, Ph), 7.42-7.46 (2H, m, Ph), 7.50 (1H, s, NH ), 7.58 (2H, d, J = 8.60 Hz, Ph), 7.70 (2H, d, J = 8.60 Hz, Ph), 7.75 (1H, d, J = 3.11 Hz, pyrazine), 7.78 (1H, d, J = 3.11 Hz, pyrazine), 11.53 (1H, s, NH)
화합물 112: 1-(3-(2-Compound 112: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.55 (2H, s, OCH2Ph), 7.07-7.12 (1H, m, Ph), 7.19 (1H, t, J = 7.26 Hz, Ph), 7.27-7.32 (1H, m, Ph), 7.37-7.41 (1H, m, Ph), 7.50-7.53 (1H, m, Ph), 7.72-7.75 (1H, m, Ph), 7.84 (1H, d, J = 3.0 Hz, pyrazine), 7.93 (1H, d, J = 3.0 Hz, pyrazine), 8.18-8.22 (1H, m, Ph), 9.26 (1H, s, NH), 11.26 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.55 (2H, s, OCH 2 Ph), 7.07-7.12 (1H, m, Ph), 7.19 (1H, t, J = 7.26 Hz, Ph), 7.27-7.32 (1H, m, Ph), 7.37-7.41 (1H, m, Ph), 7.50-7.53 (1H, m, Ph), 7.72-7.75 (1H, m, Ph), 7.84 (1H, d, J = 3.0 Hz, pyrazine), 7.93 (1H, d, J = 3.0 Hz, pyrazine), 8.18-8.22 (1H, m, Ph), 9.26 (1H, s, NH), 11.26 (1H, s, NH)
화합물 113: 1-(3-(2-Compound 113: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.54 (2H, s, OCH2Ph), 6.87-6.89 (1H, m, Ph), 7.28-7.29 (1H, m, Ph), 7.35-7.40 (3H, m, Ph), 7.50-7.53 (1H, m, Ph), 7.56-7.60 (1H, m, Ph), 7.71-7.73 (1H, m, Ph), 7.85 (1H, d, J = 3.0 Hz, pyrazine), 7.97 (1H, d, J = 3.0 Hz, pyrazine), 9.08 (1H, s, NH), 11.0 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.54 (2H, s, OCH 2 Ph), 6.87-6.89 (1H, m, Ph), 7.28-7.29 (1H, m, Ph), 7.35-7.40 (3H, m, Ph), 7.50-7.53 (1H, m, Ph), 7.56-7.60 (1H, m, Ph), 7.71-7.73 (1H, m, Ph), 7.85 (1H, d, J = 3.0 Hz, pyrazine), 7.97 (1H, d, J = 3.0 Hz, pyrazine), 9.08 (1H, s, NH), 11.0 (1H, s, NH)
화합물 114: 1-(3-(2-Compound 114: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3,4-Pyrazin-2-yl) -3- (3,4- 다이틀로로페Daitlope 닐) Neil) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.54 (2H, s, OCH2Ph), 7.37-7.39 (2H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.56 (1H, t, J = 8.78 Hz, Ph), 7.70-7.72 (1H, m, Ph), 7.86 (1H, d, J = 3.0 Hz, pyrazine), 7.96-7.89 (2H, m, pyrazine+Ph), 9.19 (1H, s, NH), 11.05 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.54 (2H, s, OCH 2 Ph), 7.37-7.39 (2H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.56 (1H , t, J = 8.78 Hz, Ph), 7.70-7.72 (1H, m, Ph), 7.86 (1H, d, J = 3.0 Hz, pyrazine), 7.96-7.89 (2H, m, pyrazine + Ph), 9.19 (1H, s, NH), 11.05 (1H, s, NH)
화합물 115: 1-(3-(2-Compound 115: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-벤질 Pyrazin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 4.60 (4.60 (2H, d, J = 5.84 Hz, OCH2Ph), 5.52 (2H, s, OCH2Ph), 7.26-7.29 (2H, m, Ph), 7.30-7.37 (5H, m, Ph), 7.40 (1H, brs, NH), 7.42-7.47 (2H, m, Ph), 7.64-7.65 (2H, m, pyrazine), 9.44 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.60 (4.60 (2H, d, J = 5.84 Hz, OCH 2 Ph), 5.52 (2H, s, OCH 2 Ph), 7.26-7.29 (2H, m, Ph ), 7.30-7.37 (5H, m, Ph), 7.40 (1H, brs, NH), 7.42-7.47 (2H, m, Ph), 7.64-7.65 (2H, m, pyrazine), 9.44 (1H, s, NH)
화합물 116: 1-(3-(2-Compound 116: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.54 (2H, s, OCH2Ph), 7.06 (1H, t, J = 7.36 Hz, Ph), 7.33 (2H, dd, J1 = 7.6 Hz, J2 = 8.27 Hz, Ph), 7.38-7.40 (2H, m, Ph), 7.507.53 (1H, m, Ph), 7.56 (2H, d, J = 7.6 Hz, Ph), 7.71-7.73 (1H, m, Ph), 7.83 (1H, d, J = 3.01 Hz, pyrazine), 7.96 (1H, d, J = 3.01 Hz, pyrazine), 8.94 (1H, s, NH), 10.91 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.54 (2H, s, OCH 2 Ph), 7.06 (1H, t, J = 7.36 Hz, Ph), 7.33 (2H, dd, J 1 = 7.6 Hz , J 2 = 8.27 Hz, Ph), 7.38-7.40 (2H, m, Ph), 7.507.53 (1H, m, Ph), 7.56 (2H, d, J = 7.6 Hz, Ph), 7.71-7.73 (1H, m , Ph), 7.83 (1H, d, J = 3.01 Hz, pyrazine), 7.96 (1H, d, J = 3.01 Hz, pyrazine), 8.94 (1H, s, NH), 10.91 (1H, s, NH)
화합물 117: 1-(3-(2-Compound 117: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.54 (2H, s, OCH2Ph), 7.11 (1H, d, J = 7.32 Hz, Ph), 7.33-7.40 (3H, m, Ph), 7.45 (1H, d, J = 8.67 Hz, Ph), 4.50-7.53 (1H, m, Ph), 7.71-7.73 (1H, m, Ph), 7.79 (1H, t, J = 1.99 Hz, Ph), 7.85 (1H, d, J = 2.92 Hz, pyrazine), 7.97 (1H, d, J = 2.92 Hz, pyrazine), 9.09 (1H, s, NH), 11.0 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.54 (2H, s, OCH 2 Ph), 7.11 (1H, d, J = 7.32 Hz, Ph), 7.33-7.40 (3H, m, Ph), 7.45 (1H, d, J = 8.67 Hz, Ph), 4.50-7.53 (1H, m, Ph), 7.71-7.73 (1H, m, Ph), 7.79 (1H, t, J = 1.99 Hz, Ph), 7.85 (1H, d, J = 2.92 Hz, pyrazine), 7.97 (1H, d, J = 2.92 Hz, pyrazine), 9.09 (1H, s, NH), 11.0 (1H, s, NH)
화합물 118: 1-(3-(2-Compound 118: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.55 (2H, s, OCH2Ph), 7.14 (2H, d, J = 8.21 Hz, Ph), 7.30-7.48 (2H, m, Ph), 7.43-7.48 (5H, m, Ph+NH), 7.72 (1H, d, J = 3.09 Hz, pyrazine), 7.77 (1H, d, J = 3.09 Hz, pyrazine), 7.93 (1H, d, J = 2.66 Hz, Ph), 11.18 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.55 (2H, s, OCH 2 Ph), 7.14 (2H, d, J = 8.21 Hz, Ph), 7.30-7.48 (2H, m, Ph), 7.43-7.48 (5H, m, Ph + NH), 7.72 (1H, d, J = 3.09 Hz, pyrazine), 7.77 (1H, d, J = 3.09 Hz, pyrazine), 7.93 (1H, d, J = 2.66 Hz, Ph), 11.18 (1H, s, NH)
화합물 119: 1-(3-(2-Compound 119: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(나프탈렌-1-일) Pyrazin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.58 (2H, OCH2Ph), 7.39-7.41 (2H, m, Ph), 7.52-7.67 (4H, m, Ph), 7.72 (1H, d, J = 8.14 Hz, Ph), 7.75-7.78 (1H, m, Ph), 7.88 (1H, d, J = 2.98 Hz, pyrazine), 7.98 (1H, d, J = 8.14 Hz, Ph), 8.09 (1H, d, J = 2.98 Hz, pyrazine), 8.12-8.15 (2H, m, Ph), 9.21 (1H, s, NH), 11.62 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.58 (2H, OCH 2 Ph), 7.39-7.41 (2H, m, Ph), 7.52-7.67 (4H, m, Ph), 7.72 (1H, d , J = 8.14 Hz, Ph), 7.75-7.78 (1H, m, Ph), 7.88 (1H, d, J = 2.98 Hz, pyrazine), 7.98 (1H, d, J = 8.14 Hz, Ph), 8.09 ( 1H, d, J = 2.98 Hz, pyrazine), 8.12-8.15 (2H, m, Ph), 9.21 (1H, s, NH), 11.62 (1H, s, NH)
화합물 120: 1-(3-(3-Compound 120: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.47 (2H, s, OCH2Ph), 7.08-7.10 (1H, m, Ph), 7.17-7.21 (1H, t, J = 7.60 Hz, Ph), 7.27-7.32 (1H, m, Ph), 7.39-7.44 (2H, m, Ph), 7.51 (1H, d, J = 6.71 Hz, Ph), 7.40 (1H, s, Ph), 7.82 (1H, d, J = 3.02 Hz, pyrazine), 7.90 (1H, d, J = 3.02 Hz, pyrazine), 8.19-8.23 (1H, m, Ph), 9.36 (1H, s, NH), 11.32 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.47 (2H, s, OCH 2 Ph), 7.08-7.10 (1H, m, Ph), 7.17-7.21 (1H, t, J = 7.60 Hz, Ph ), 7.27-7.32 (1H, m, Ph), 7.39-7.44 (2H, m, Ph), 7.51 (1H, d, J = 6.71 Hz, Ph), 7.40 (1H, s, Ph), 7.82 (1H , d, J = 3.02 Hz, pyrazine), 7.90 (1H, d, J = 3.02 Hz, pyrazine), 8.19-8.23 (1H, m, Ph), 9.36 (1H, s, NH), 11.32 (1H, s , NH)
화합물 121: 1-(3-(3-Compound 121: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.46 (2H, s, OCH2Ph), 6.86-6.88 (1H, m, Ph), 7.28-7.41 (4H, m, Ph), 7.50 (1H, d, J = 6.49 Hz, Ph), 7.58-7.61 (1H, m, Ph), 7.68 (1H, brs, Ph), 7.83 (1H, d, J = 2.98 Hz, pyrazine), 7.95 (1H, d, J = 2.98 Hz, pyrazine), 9.19 (1H, s, NH), 11.06 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.46 (2H, s, OCH 2 Ph), 6.86-6.88 (1H, m, Ph), 7.28-7.41 (4H, m, Ph), 7.50 (1H , d, J = 6.49 Hz, Ph), 7.58-7.61 (1H, m, Ph), 7.68 (1H, brs, Ph), 7.83 (1H, d, J = 2.98 Hz, pyrazine), 7.95 (1H, d , J = 2.98 Hz, pyrazine), 9.19 (1H, s, NH), 11.06 (1H, s, NH)
화합물 122: 1-(3-(3-Compound 122: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3,4-Pyrazin-2-yl) -3- (3,4- 다이틀로로페Daitlope 닐) Neil) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.46 (2H, s, OCH2Ph), 7.38-7.42 (2H, m, Ph), 7.47-7.59 (3H, m, Ph), 7.68 (1H, brs, Ph), 7.84 (1H, d, J = 2.96 Hz, pyrazine), 7.95 (1H, d, J = 2.96 Hz, pyrazine), 7.99 (1H, d, J = 2.29 Hz, Ph), 9.28 (1H, s, NH), 11.10 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.46 (2H, s, OCH 2 Ph), 7.38-7.42 (2H, m, Ph), 7.47-7.59 (3H, m, Ph), 7.68 (1H , brs, Ph), 7.84 (1H, d, J = 2.96 Hz, pyrazine), 7.95 (1H, d, J = 2.96 Hz, pyrazine), 7.99 (1H, d, J = 2.29 Hz, Ph), 9.28 ( 1H, s, NH), 11.10 (1H, s, NH)
화합물 123: 1-(3-(3-Compound 123: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-벤질 Pyrazin-2-yl) -3-benzyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 4.60 (2H, d, J = 5.84 Hz, OCH2Ph), 5.39 (2H, s, OCH2Ph), 7.26-7.29 (1H, m, Ph), 7.30-7.37 (7H, m, Ph), 7.40 (1H, brs, NH), 7.41 (1H, brs, Ph), 7.63 (1H, d, J = 3.1 Hz, pyrazine), 7.64 (1H, d, J = 3.1 Hz, Ph), 9.42 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.60 (2H, d, J = 5.84 Hz, OCH 2 Ph), 5.39 (2H, s, OCH 2 Ph), 7.26-7.29 (1H, m, Ph), 7.30-7.37 (7H, m, Ph), 7.40 (1H, brs, NH), 7.41 (1H, brs, Ph), 7.63 (1H, d, J = 3.1 Hz, pyrazine), 7.64 (1H, d, J = 3.1 Hz, Ph), 9.42 (1H, s, NH)
화합물 124: 1-(3-(3-Compound 124: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 페닐Phenyl 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.46 (2H, s, OCH2Ph), 7.06 (1H, t, J = 7.37 Hz, Ph), 7.33 (2H, t, J = 7.81 Hz, Ph), 7.40-7.44 (2H, m, Ph), 7.51 (1H, d, J = 6.64 Hz, Ph), 7.57 (2H, d, J = 8.23 Hz, Ph), 7.69 (1H, s, Ph), 7.81 (1H, d, J = 3.0 Hz, pyrazine), 7.93 (1H, d, J = 3.0 Hz, pyrazine), 9.05 (1H, s, NH), 10.97 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.46 (2H, s, OCH 2 Ph), 7.06 (1H, t, J = 7.37 Hz, Ph), 7.33 (2H, t, J = 7.81 Hz, Ph), 7.40-7.44 (2H, m, Ph), 7.51 (1H, d, J = 6.64 Hz, Ph), 7.57 (2H, d, J = 8.23 Hz, Ph), 7.69 (1H, s, Ph) , 7.81 (1H, d, J = 3.0 Hz, pyrazine), 7.93 (1H, d, J = 3.0 Hz, pyrazine), 9.05 (1H, s, NH), 10.97 (1H, s, NH)
화합물 125: 1-(3-(3-Compound 125: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.46 (2H, s, OCH2Ph), 7.10 (1H, m, Ph), 7.35 (1H, t, J = 8.09 Hz, Ph), 7.407.41 (2H, m, Ph), 7.45 (1H, d, J = 8.26 Hz, Ph), 7.50 (1H, d, J = 6.44 Hz, Ph), 7.68 (1H, brs, Ph), 7.80 (1H, t, J = 1.90 Hz, Ph), 7.83 (1H, d, J = 2.99 Hz, pyrazine), 7.95 (1H, d, J = 2.99 Hz, Ph), 9.20 (1H, s, NH), 11.06 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.46 (2H, s, OCH 2 Ph), 7.10 (1H, m, Ph), 7.35 (1H, t, J = 8.09 Hz, Ph), 7.407. 41 (2H, m, Ph), 7.45 (1H, d, J = 8.26 Hz, Ph), 7.50 (1H, d, J = 6.44 Hz, Ph), 7.68 (1H, brs, Ph), 7.80 (1H, t, J = 1.90 Hz, Ph), 7.83 (1H, d, J = 2.99 Hz, pyrazine), 7.95 (1H, d, J = 2.99 Hz, Ph), 9.20 (1H, s, NH), 11.06 (1H , s, NH)
화합물 126: 1-(3-(3-Compound 126: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 2.26 (3H, s, CH3), 5.46 (2H, s, OCH2Ph), 7.13 (2H, d, J = 8.34 Hz, Ph), 7.39-7.41 (2H, m, Ph), 7.45 (2H, d, J = 8.34 Hz, Ph), 7.50 (1H, d, J = 6.60 Hz, Ph), 7.69 (1H, s, Ph), 7.80 (1H, d, J = 3.02 Hz, pyrazine), 7.92 (1H, d, J = 3.02 Hz, pyrazine), 8.99 (1H, s, NH), 10.93 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 2.26 (3H, s, CH 3 ), 5.46 (2H, s, OCH 2 Ph), 7.13 (2H, d, J = 8.34 Hz, Ph), 7.39 -7.41 (2H, m, Ph), 7.45 (2H, d, J = 8.34 Hz, Ph), 7.50 (1H, d, J = 6.60 Hz, Ph), 7.69 (1H, s, Ph), 7.80 (1H , d, J = 3.02 Hz, pyrazine), 7.92 (1H, d, J = 3.02 Hz, pyrazine), 8.99 (1H, s, NH), 10.93 (1H, s, NH)
화합물 127: 1-(3-(3-Compound 127: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(나프탈렌-1-일) Pyrazin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.46 (2H, s, OCH2Ph), 7.36 (3H, d, J = 1.12 Hz, Ph), 7.46-7.57 (4H, m, Ph), 7.60 (1H, brs, NH), 7.68 (1H, d, J = 8.19 Hz, Ph), 7.77 (1H, d, J = 3.08 Hz, pyrzaine), 7.88 (1H, d, J = 3.08, pyrzaine), 7.90 (1H, s, Ph), 8.12 (1H, d, J = 8.45, Ph), 8.16 (1H, d, J =6.79 Hz, Ph), 11.76 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.46 (2H, s, OCH 2 Ph), 7.36 (3H, d, J = 1.12 Hz, Ph), 7.46-7.57 (4H, m, Ph), 7.60 ( 1H, brs, NH), 7.68 (1H, d, J = 8.19 Hz, Ph), 7.77 (1H, d, J = 3.08 Hz, pyrzaine), 7.88 (1H, d, J = 3.08, pyrzaine), 7.90 ( 1H, s, Ph), 8.12 (1H, d, J = 8.45, Ph), 8.16 (1H, d, J = 6.79 Hz, Ph), 11.76 (1H, s, NH)
화합물 128: 1-(3-(4-Compound 128: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.42 (2H, s, OCH2Ph), 7.03-7.16 (3H, m, Ph), 7.36-7.41 (4H, m, Ph), 7.48 (1H, s, NH), 7.71 (1H, d, J = 3.04 Hz, pyrazine), 7.79 (1H, d, J = 3.04 Hz, pyrazine), 8.26-8.30 (1H, m, Ph), 11.60 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.42 (2H, s, OCH 2 Ph), 7.03-7.16 (3H, m, Ph), 7.36-7.41 (4H, m, Ph), 7.48 (1H, s , NH), 7.71 (1H, d, J = 3.04 Hz, pyrazine), 7.79 (1H, d, J = 3.04 Hz, pyrazine), 8.26-8.30 (1H, m, Ph), 11.60 (1H, s, NH )
화합물 129: 1-(3-(4-Compound 129: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 플루오르페닐Fluorophenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.29 (2H, s, OCH2Ph), 6.79 (1H, m, Ph), 7.22-7.28 (2H, m, Ph), 7.36-7.40 (4H, m, Ph), 7.47 (1H, s, NH), 7.49-7.52 (1H, m, Ph), 7.72 (1H, d, J = 3.2 Hz, pyrazine), 7.77 (1H, d, J = 3.2 Hz, pyrazine), 11.38 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.29 (2H, s, OCH 2 Ph), 6.79 (1H, m, Ph), 7.22-7.28 (2H, m, Ph), 7.36-7.40 (4H, m , Ph), 7.47 (1H, s, NH), 7.49-7.52 (1H, m, Ph), 7.72 (1H, d, J = 3.2 Hz, pyrazine), 7.77 (1H, d, J = 3.2 Hz, pyrazine ), 11.38 (1H, s, NH)
화합물 130: 1-(3-(4-Compound 130: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3,4-Pyrazin-2-yl) -3- (3,4- 다이클로로페Dichlorofe 닐) Neil) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.45 (2H, s, OCH2Ph), 7.44 (2H, d, J = 8.44 Hz, Ph), 7.52 (1H, dd, J1= 2.36 Hz, J2 = 8.8 Hz, Ph), 7.57 (3H, d, J = 8.8 Hz, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.94 (1H, d, J = 3.0 Hz, Ph), 7.98 (1H, d, J = 2.36 Hz, Ph), 9.21 (1H, s, NH), 11.11 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.45 (2H, s, OCH 2 Ph), 7.44 (2H, d, J = 8.44 Hz, Ph), 7.52 (1H, dd, J 1 = 2.36 Hz , J 2 = 8.8 Hz, Ph), 7.57 (3H, d, J = 8.8 Hz, Ph), 7.83 (1H, d, J = 3.0 Hz, pyrazine), 7.94 (1H, d, J = 3.0 Hz, Ph ), 7.98 (1H, d, J = 2.36 Hz, Ph), 9.21 (1H, s, NH), 11.11 (1H, s, NH)
화합물 131: 1-(3-(4-Compound 131: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 5.41 (2H, s, OCH2Ph), 7.14 (2H, d, J = 8.4 Hz, Ph), 7.35-7.40 (4H, m, Ph), 7.42 (1H, s, NH), 7.44 (2H, d, J = 8.4 Hz, Ph), 7.69 (1H, d, J = 3.2 Hz, pyrazine), 7.75 (1H, d, J = 3.2 Hz, pyrazine), 11.14 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 5.41 (2H, s, OCH 2 Ph), 7.14 (2H, d, J = 8.4 Hz, Ph), 7.35-7.40 (4H, m, Ph), 7.42 (1H, s, NH), 7.44 (2H, d, J = 8.4 Hz, Ph), 7.69 (1H, d, J = 3.2 Hz, pyrazine), 7.75 (1H, d , J = 3.2 Hz, pyrazine), 11.14 (1H, s, NH)
화합물 132: 1-(3-(4-Compound 132: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(나프탈렌-1-일) Pyrazin-2-yl) -3- (naphthalen-1-yl) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 5.49 (2H, s, OCH2Ph), 7.45-7.54 (5H, m, Ph), 7.56-7.75 (7H, m, Ph), 7.85 (1H, d, J = 3.04 Hz, Pyrazine), 7.91-7.93 (1H, m, Ph), 8.04-8.07 (2H, m, pyrazine+Ph), 8.13 (2H, t, J = 7.45 Hz, Ph), 9.24 (1H, s, NH), 9.53 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 5.49 (2H, s, OCH 2 Ph), 7.45-7.54 (5H, m, Ph), 7.56-7.75 (7H, m, Ph), 7.85 (1H , d, J = 3.04 Hz, Pyrazine), 7.91-7.93 (1H, m, Ph), 8.04-8.07 (2H, m, pyrazine + Ph), 8.13 (2H, t, J = 7.45 Hz, Ph), 9.24 (1H, s, NH), 9.53 (1H, s, NH)
화합물 133: 1-(3-(4-Compound 133: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(4-(Pyrazin-2-yl) -3- (4- ( 트리플루오르메Trifluoromethane 틸)Yl) 페닐Phenyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 5.43 (2H, s, OCH2Ph), 7.27-7.29 (2H, m, Ph), 7.38-7.40 (4H, m, Ph), 7.48 (1H, s, NH), 7.59 (2H, d, J = 7.6 Hz, Ph), 7.71, (2H, d, J = 7.6 Hz, Ph), 7.75 (1H, d, J = 3.2 Hz, pyrazine), 7.79 (1H, d, J = 3.2 Hz, pyrazine), 11.52 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.43 (2H, s, OCH 2 Ph), 7.27-7.29 (2H, m, Ph), 7.38-7.40 (4H, m, Ph), 7.48 (1H, s , NH), 7.59 (2H, d, J = 7.6 Hz, Ph), 7.71, (2H, d, J = 7.6 Hz, Ph), 7.75 (1H, d, J = 3.2 Hz, pyrazine), 7.79 (1H , d, J = 3.2 Hz, pyrazine), 11.52 (1H, s, NH)
실시예Example 5. 1-(3-( 5. 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(Pyrazin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
3-(3-벤질옥시)피리딘-2-아민 (100 mg, 0.50 mmol)과 수소화나트륨 (60% in mineral oil, 22 mg, 0.55 mmol)을 테트라하이드로퓨란(0.25M)에 녹인 후, 1-아다만틸 아이소시아네이트 (106 mg, 0.6 mmol)를 적가 한 후 20 시간 동안 가열 환류 시킨다. 반응물을 실온까지 식히고 물을 넣어 반응을 종결시킨 후, 초산에틸로 추출한 뒤, 추출한 용액을 황산 나트륨으로 건조하고, 감압 여과하여 감압 농축한다. 잔여물을 컬럼크로마토그래피법 (초산에틸/노르말헥산 =1/2)으로 분리 정제하여 26.6 %의 수율로 목적화합물 50 mg을 얻었다.3- (3-benzyloxy) pyridin-2-amine (100 mg, 0.50 mmol) and sodium hydride (60% in mineral oil, 22 mg, 0.55 mmol) were dissolved in tetrahydrofuran (0.25M), followed by 1- Adamantyl isocyanate (106 mg, 0.6 mmol) was added dropwise and heated to reflux for 20 hours. The reaction was cooled to room temperature, water was added to terminate the reaction, and extracted with ethyl acetate. The extracted solution was dried over sodium sulfate, filtered under reduced pressure and concentrated under reduced pressure. The residue was separated and purified by column chromatography (ethyl acetate / normal hexane = 1/2) to obtain 50 mg of the title compound in a yield of 26.6%.
1H NMR (400 MHz, CDCl3) δ = 1.70 (4H, s, adamantyl), 2.08 (9H, s, adamantyl), 5.40 (2H, s, OCH2Ph), 7.15 (1H, s, NH), 7.35-7.42 (5H, m, Ph), 7.60 (1H, d, J = 3.07 Hz, pyrazine), 7.62 (1H, d, J = 3.07 Hz, pyrazine) 9.05 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.70 (4H, s, adamantyl), 2.08 (9H, s, adamantyl), 5.40 (2H, s, OCH 2 Ph), 7.15 (1H, s, NH), 7.35-7.42 (5H, m, Ph), 7.60 (1H, d, J = 3.07 Hz, pyrazine), 7.62 (1H, d, J = 3.07 Hz, pyrazine) 9.05 (1H, s, NH)
이하, 하기 화합물 134 내지 161을 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
Hereinafter, the following Compounds 134 to 161 were obtained by a method similar to the above Example, and the analysis results of these compounds were as follows:
화합물 134: 1-(3-(Compound 134: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(Pyrazin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.70 (4H, s, adamantyl), 2.08 (9H, s, adamantyl), 5.40 (2H, s, OCH2Ph), 7.15 (1H, s, NH), 7.35-7.42 (5H, m, Ph), 7.60 (1H, d, J = 3.07 Hz, pyrazine), 7.62 (1H, d, J = 3.07 Hz, pyrazine) 9.05 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.70 (4H, s, adamantyl), 2.08 (9H, s, adamantyl), 5.40 (2H, s, OCH 2 Ph), 7.15 (1H, s, NH), 7.35-7.42 (5H, m, Ph), 7.60 (1H, d, J = 3.07 Hz, pyrazine), 7.62 (1H, d, J = 3.07 Hz, pyrazine) 9.05 (1H, s, NH)
화합물 135: 1-(3-(Compound 135: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.52-1.64 (10H, m, Cycloheptyl), 1.95-2.00 (2H, m, Cycloheptyl), 3.98-4.01 (1H, m, Cycloheptyl), 5.40 (2H, s, OCH2Ph), 7.28 (1H, s, NH) 7.35-7.43 (5H, m, Ph), 7.63 (1H, d, J = 3.12 Hz, pyrazine), 7.66 (1H, d, J = 3.12Hz, pyrazine) ,9.07 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.52-1.64 (10H, m, Cycloheptyl), 1.95-2.00 (2H, m, Cycloheptyl), 3.98-4.01 (1H, m, Cycloheptyl), 5.40 (2H, s , OCH 2 Ph), 7.28 (1H, s, NH) 7.35-7.43 (5H, m, Ph), 7.63 (1H, d, J = 3.12 Hz, pyrazine), 7.66 (1H, d, J = 3.12 Hz, pyrazine), 9.07 (1H, s, NH)
화합물 136: 1-(3-(Compound 136: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(2,4,4-Pyrazin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) 유레아-2- day) urea
1H NMR (400 MHz, CDCl3) δ = 1.01 (9H, s, 3CH3), 1.47 (6H, s, 2CH3), 1.80 (2H, s, CH2), 5.40 (2H, s, OCH2Ph), 7.15 (1H, s,NH), 7.35-7.43 (5H, m, Ph), 7.61 (1H, d, J = 3.13 Hz, pyrazine), 7.63 (1H, d, J = 3.13 Hz, pyrazine), 9.05 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.01 (9H, s, 3CH 3 ), 1.47 (6H, s, 2CH 3 ), 1.80 (2H, s, CH 2 ), 5.40 (2H, s, OCH 2 Ph), 7.15 (1H, s, NH), 7.35-7.43 (5H, m, Ph), 7.61 (1H, d, J = 3.13 Hz, pyrazine), 7.63 (1H, d, J = 3.13 Hz, pyrazine) , 9.05 (1H, s, NH)
화합물 137: 1-(3-(Compound 137: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-에틸 ) Pyrazin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.23 (3H, t, J = 7.26 Hz, CH3), 3.37-3.44 (2H, m, CH2), 5.40 (2H, s, OCH2Ph), 7.32 (1H, s, NH), 7.36-7.43 (5H, m, Ph), 7.64 (1H, d, J = 3.11 Hz, pyrazine), 7.66 (1H, d, J = 3.11 Hz, pyrazine), 9.10 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.23 (3H, t, J = 7.26 Hz, CH 3 ), 3.37-3.44 (2H, m, CH 2 ), 5.40 (2H, s, OCH 2 Ph), 7.32 (1H, s, NH), 7.36-7.43 (5H, m, Ph), 7.64 (1H, d, J = 3.11 Hz, pyrazine), 7.66 (1H, d, J = 3.11 Hz, pyrazine), 9.10 ( 1H, s, NH)
화합물 138: 1-(3-(Compound 138: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.42 (9H, s, 3CH3), 5.40 (2H, s, OCH2Ph), 7.17 (1H, s, NH), 7.35-7.42 (5H, m, Ph), 7.61 (1H, d, J = 3.12 Hz, pyrazine), 7.66 (1H, d, J = 3.12 Hz, pyrazine), 9.01 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.42 (9H, s, 3CH 3 ), 5.40 (2H, s, OCH 2 Ph), 7.17 (1H, s, NH), 7.35-7.42 (5H, m, Ph), 7.61 (1H, d, J = 3.12 Hz, pyrazine), 7.66 (1H, d, J = 3.12 Hz, pyrazine), 9.01 (1H, s, NH)
화합물 139: 1-(3-(3-Compound 139: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(Pyrazin-2-yl) -3- ( 아다만탄Adamantan -1-일) 유레아-1-yl) urea
1H NMR (400 MHz, CDCl3) δ = 1.70 (5H, s, adamantyl), 2.09 (9H, s, adamantyl), 5.40 (2H, s, OCH2Ph), 7.01-7.06 (1H, m, Ph), 7.10-7.13 (2H, m, Ph), 7.19 (1H, d, J = 7.61, Ph), 7.32-7.37 (1H, m, Ph), 7.59 (1H, d, J = 3.10 Hz, pyrazine), 7.65 (1H, d, J = 3.10 Hz, pyrazine), 8.92 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.70 (5H, s, adamantyl), 2.09 (9H, s, adamantyl), 5.40 (2H, s, OCH 2 Ph), 7.01-7.06 (1H, m, Ph ), 7.10-7.13 (2H, m, Ph), 7.19 (1H, d, J = 7.61, Ph), 7.32-7.37 (1H, m, Ph), 7.59 (1H, d, J = 3.10 Hz, pyrazine) , 7.65 (1H, d, J = 3.10 Hz, pyrazine), 8.92 (1H, s, NH)
화합물 140: 1-(3-(3-Compound 140: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.52-1.65 (10H, m, Cycloheptyl), 1.96-2.00 (2H, m, Cycloheptyl), 3.98-4.02 (1H, m, Cycloheptyl), 5.40 (2H, s, OCH2Ph), 7.02-7.07 (1H, m, Ph), 7.11-7.14 (1H, m, Ph), 7.19 (1H, d, J = 7.80 Hz, Ph), 7.27 (1H, s, NH), 7.32-7.38 (1H, m, Ph), 7.62 (1H, d, J = 3.11 Hz, pyrazine), 7.66 (1H, d, J = 3.11Hz, pyrazine), 9.05 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.52-1.65 (10H, m, Cycloheptyl), 1.96-2.00 (2H, m, Cycloheptyl), 3.98-4.02 (1H, m, Cycloheptyl), 5.40 (2H, s , OCH 2 Ph), 7.02-7.07 (1H, m, Ph), 7.11-7.14 (1H, m, Ph), 7.19 (1H, d, J = 7.80 Hz, Ph), 7.27 (1H, s, NH) , 7.32-7.38 (1H, m, Ph), 7.62 (1H, d, J = 3.11 Hz, pyrazine), 7.66 (1H, d, J = 3.11 Hz, pyrazine), 9.05 (1H, s, NH)
화합물 141: 1-(3-(3-Compound 141: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(2,4,4-Pyrazin-2-yl) -3- (2,4,4- 트리메틸펜Trimethylphene 탄-2-일) Tan-2-yl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.01 (9H, s, 3CH3), 1.48 (6H, s, 2CH3), 1.80 (2H, s, CH2), 5.39 (2H, s, OCH2Ph), 7.03-7.07 (1H, m, Ph), 7.10-7.13 (2H, m, Ph+NH), 7.19 (1H, d, J = 7.59 Hz, Ph), 7.32-7.38 (1H, m, Ph), 7.60 (1H, d, J = 3.13 Hz, pyrazine), 7.65 (1H, d, J = 3.13 Hz, pyrazine), 9.03 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.01 (9H, s, 3CH 3 ), 1.48 (6H, s, 2CH 3 ), 1.80 (2H, s, CH 2 ), 5.39 (2H, s, OCH 2 Ph), 7.03-7.07 (1H, m, Ph), 7.10-7.13 (2H, m, Ph + NH), 7.19 (1H, d, J = 7.59 Hz, Ph), 7.32-7.38 (1H, m, Ph ), 7.60 (1H, d, J = 3.13 Hz, pyrazine), 7.65 (1H, d, J = 3.13 Hz, pyrazine), 9.03 (1H, s, NH)
화합물 142: 1-(3-(3-Compound 142: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-에틸 ) Pyrazin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.24 (3H, t, J = 7.25 Hz, CH3), 3.38-3.45 (2H, m, CH2), 5.40 (2H, s, OCH2Ph), 7.04-7.06 (1H, m, Ph), 7.11-7.14 (1H, m, Ph), 7.19 (1H, d, J = 7.6 Hz, Ph), 7.31 (1H, s, NH), 7.32-7.37 (1H, m, Ph), 7.63 (1H, d, J = 3.10 Hz, pyrazine), 7.68 (1H, d, J = 3.10 Hz, pyrazine), 9.12 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.24 (3H, t, J = 7.25 Hz, CH 3 ), 3.38-3.45 (2H, m, CH 2 ), 5.40 (2H, s, OCH 2 Ph), 7.04-7.06 (1H, m, Ph), 7.11-7.14 (1H, m, Ph), 7.19 (1H, d, J = 7.6 Hz, Ph), 7.31 (1H, s, NH), 7.32-7.37 (1H , m, Ph), 7.63 (1H, d, J = 3.10 Hz, pyrazine), 7.68 (1H, d, J = 3.10 Hz, pyrazine), 9.12 (1H, s, NH)
화합물 143: 1-(3-(3-Compound 143: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.43 (9H, s, 3CH3), 5.40 (2H, s, OCH2Ph), 7.03-7.05 (1H, m, Ph), 7.10-7.13 (1H, m, Ph), 7.15 (1H, s, NH), 7.19 (1H, J = 7.39 Hz, Ph), 7.32-7.36 (1H, m, Ph), 7.60 (1H, d, J = 3.14 Hz, pyrazine), 7.66 (1H, d, J = 3.14 Hz, pyrazine), 8.99 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.43 (9H, s, 3CH 3 ), 5.40 (2H, s, OCH 2 Ph), 7.03-7.05 (1H, m, Ph), 7.10-7.13 (1H, m, Ph), 7.15 (1H, s, NH), 7.19 (1H, J = 7.39 Hz, Ph), 7.32-7.36 (1H, m, Ph), 7.60 (1H, d, J = 3.14 Hz, pyrazine) , 7.66 (1H, d, J = 3.14 Hz, pyrazine), 8.99 (1H, s, NH)
화합물 144: 1-(3-(4-Compound 144: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.58-1.61 (10H, m, Cycloheptyl), 1.97-2.02 (2H, m, Cycloheptyl), 3.99-4.00 (1H, m, Cycloheptyl), 5.37 (2H, s, OCH2Ph), 7.05-7.09 (3H, m, Ph+NH), 7.39-7.42 (3H, m, Ph+NH), 7.62 (1H, d, J = 3.2 Hz, pyrazine), 7.67 (1H, d, J = 3.2 Hz, pyrazine), 9.05 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.58-1.61 (10H, m, Cycloheptyl), 1.97-2.02 (2H, m, Cycloheptyl), 3.99-4.00 (1H, m, Cycloheptyl), 5.37 (2H, s , OCH 2 Ph), 7.05-7.09 (3H, m, Ph + NH), 7.39-7.42 (3H, m, Ph + NH), 7.62 (1H, d, J = 3.2 Hz, pyrazine), 7.67 (1H, d, J = 3.2 Hz, pyrazine), 9.05 (1H, s, NH)
화합물 145: 1-(3-(4-Compound 145: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(2,4,4-Pyrazin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.01 (9H, s, 3CH3), 1.47 (6H, s, 2CH3), 1.80 (2H, s, CH2), 5.36 (2H, s, OCH2Ph), 7.06 (2H, t, J = 8.4 Hz, Ph), 7.12 (1H, brs, NH), 7.39-7.42 (2H, m, Ph), 7.60 (1H, d, J = 3.2 Hz, pyrazine), 7.64 (1H, d, J = 3.2 Hz, pyrazine), 9.03 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.01 (9H, s, 3CH 3 ), 1.47 (6H, s, 2CH 3 ), 1.80 (2H, s, CH 2 ), 5.36 (2H, s, OCH 2 Ph), 7.06 (2H, t, J = 8.4 Hz, Ph), 7.12 (1H, brs, NH), 7.39-7.42 (2H, m, Ph), 7.60 (1H, d, J = 3.2 Hz, pyrazine) , 7.64 (1H, d, J = 3.2 Hz, pyrazine), 9.03 (1H, s, NH)
화합물 146: 1-(3-(4-Compound 146: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-에틸 ) Pyrazin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.23 (3H, t, J = 7.2 Hz, CH3), 3.37-3.44 (2H, m, CH2), 5.37 (2H, s, OCH2Ph), 7.07 (2H, t, J = 8.4 Hz, Ph), 7.30 (1H, s, NH), 7.39-7.42 (2H, m, Ph), 7.63 (1H, d, J = 3.2 Hz, pyrazine), 7.67 (1H, d, J = 3.2 Hz, pyrazine), 8.97 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.23 (3H, t, J = 7.2 Hz, CH 3 ), 3.37-3.44 (2H, m, CH 2 ), 5.37 (2H, s, OCH 2 Ph), 7.07 (2H, t, J = 8.4 Hz, Ph), 7.30 (1H, s, NH), 7.39-7.42 (2H, m, Ph), 7.63 (1H, d, J = 3.2 Hz, pyrazine), 7.67 ( 1H, d, J = 3.2 Hz, pyrazine), 8.97 (1H, s, NH)
화합물 147: 1-(3-(4-Compound 147: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.42 (9H, s, 3CH3), 5.37 (2H, s, OCH2Ph), 7.06 (2H, t, J = 8.4 Hz, Ph), 7.14 (1H, s, NH), 7.38-7.42 (2H, n, Ph), 7.60 (1H, d, J = 3.2 Hz, pyrazine), 7.65 (1H, d, J = 3.2 Hz, pyrazine), 8.99 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.42 (9H, s, 3CH 3 ), 5.37 (2H, s, OCH 2 Ph), 7.06 (2H, t, J = 8.4 Hz, Ph), 7.14 (1H , s, NH), 7.38-7.42 (2H, n, Ph), 7.60 (1H, d, J = 3.2 Hz, pyrazine), 7.65 (1H, d, J = 3.2 Hz, pyrazine), 8.99 (1H, s , NH)
화합물 148: 1-(3-(2-Compound 148: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(Pyrazin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 1.65 (5H, s, adamantyl), 2.09 (9H, s, adamantyl), 5.51 (2H, s, OCH2Ph), 7.13 (1H, brs, NH), 7.27-7.31 (2H, m, Ph), 7,41-7.45 (2H, m, Ph), 7.61 (1H, d, J = 3.1, pyrazine), 7.77 (1H, d, J = 3.1 Hz, pyrazine), 8.94 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 1.65 (5H, s, adamantyl), 2.09 (9H, s, adamantyl), 5.51 (2H, s, OCH 2 Ph), 7.13 (1H, brs, NH ), 7.27-7.31 (2H, m, Ph), 7,41-7.45 (2H, m, Ph), 7.61 (1H, d, J = 3.1, pyrazine), 7.77 (1H, d, J = 3.1 Hz, pyrazine), 8.94 (1H, s, NH)
화합물 149: 1-(3-(2-Compound 149: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.55-1.65 (10H, m, Cycloheptyl), 1.96-2.04 (2H, m, Cycloheptyl), 3.98-4.02 (1H, m, Cycloheptyl), 5.51 (2H, s, OCH2Ph), 7.27-7.34 (3H, m, Ph+NH), 7.42-7.45 (2H, m, Ph), 7.63 (1H, d, J = 3.11 Hz, pyrazine), 7.69 (1H, d, J = 3.11 Hz, pyrazine), 9.08 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.55-1.65 (10H, m, Cycloheptyl), 1.96-2.04 (2H, m, Cycloheptyl), 3.98-4.02 (1H, m, Cycloheptyl), 5.51 (2H, s , OCH 2 Ph), 7.27-7.34 (3H, m, Ph + NH), 7.42-7.45 (2H, m, Ph), 7.63 (1H, d, J = 3.11 Hz, pyrazine), 7.69 (1H, d, J = 3.11 Hz, pyrazine), 9.08 (1H, s, NH)
화합물 150: 1-(3-(2-Compound 150: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2,4,4-Pyrazin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.02 (9H, s, 3CH3), 1.48 (6H, s, 2CH3), 1.80 (2H, s, CH2), 5.51 (2H, s, OCH2Ph), 7.14 (1H, s, NH), 7.28-7.31 (2H, m, Ph), 7.41-7.46 (2H, m, Ph), 7.61 (1H, d, J = 3.08 Hz, pyrazine), 7.66 (1H, d, J = 3.08 Hz, pyrazine), 9.05 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.02 (9H, s, 3CH 3 ), 1.48 (6H, s, 2CH 3 ), 1.80 (2H, s, CH 2 ), 5.51 (2H, s, OCH 2 Ph), 7.14 (1H, s, NH), 7.28-7.31 (2H, m, Ph), 7.41-7.46 (2H, m, Ph), 7.61 (1H, d, J = 3.08 Hz, pyrazine), 7.66 ( 1H, d, J = 3.08 Hz, pyrazine), 9.05 (1H, s, NH)
화합물 151: 1-(3-(2-Compound 151: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-에틸 ) Pyrazin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.24 (3H, t, J = 7.24 Hz, CH3), 3.38-3.45 (2H, m, CH2), 5.51 (2H, s, OCH2Ph), 7.27-7.34 (3H, m, Ph+NH), 7.42-7.46 (2H, m, Ph), 7.65 (1H, d, J = 3.11 Hz, pyrazine), 7.69 (1H, d, J = 3.11 Hz, pyrazine), 9.0 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.24 (3H, t, J = 7.24 Hz, CH 3 ), 3.38-3.45 (2H, m, CH 2 ), 5.51 (2H, s, OCH 2 Ph), 7.27-7.34 (3H, m, Ph + NH), 7.42-7.46 (2H, m, Ph), 7.65 (1H, d, J = 3.11 Hz, pyrazine), 7.69 (1H, d, J = 3.11 Hz, pyrazine ), 9.0 (1H, s, NH)
화합물 152: 1-(3-(2-Compound 152: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.43 (9H, s, 3CH3), 5.51 (2H, s, OCH2Ph), 7.16 (1H, brs, NH), 7.28-7.33 (2H, m, Ph), 7.41-7.45 (2H, m, Ph), 7.61 (1H, d, J = 3.08 Hz, pyrazine), 7.66 (1H, d, J = 3.08 Hz, pyrazine), 9.01 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.43 (9H, s, 3CH 3 ), 5.51 (2H, s, OCH 2 Ph), 7.16 (1H, brs, NH), 7.28-7.33 (2H, m, Ph), 7.41-7.45 (2H, m, Ph), 7.61 (1H, d, J = 3.08 Hz, pyrazine), 7.66 (1H, d, J = 3.08 Hz, pyrazine), 9.01 (1H, s, NH)
화합물 153: 1-(3-(3-Compound 153: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(Pyrazin-2-yl) -3- ( 아다만탄Adamantan -1-일) -1 day) 유레아Urea
1H NMR (400 MHz, DMSO-d6) δ = 1.65 (5H, s, adamantyl), 2.00 (9H, s, adamantyl), 5.42 (2H, s, OCH2Ph), 7.39-7.45 (3H, m, Ph), 7.65-7.66 (1H, m, Ph), 7.69 (1H, d, J = 3.14, pyrazine), 7.77 (1H, d, J = 3.14 Hz, pyrazine), 8.22 (1H, s, NH), 8.79 (1H, s, NH)
1 H NMR (400 MHz, DMSO-d 6 ) δ = 1.65 (5H, s, adamantyl), 2.00 (9H, s, adamantyl), 5.42 (2H, s, OCH 2 Ph), 7.39-7.45 (3H, m , Ph), 7.65-7.66 (1H, m, Ph), 7.69 (1H, d, J = 3.14, pyrazine), 7.77 (1H, d, J = 3.14 Hz, pyrazine), 8.22 (1H, s, NH) , 8.79 (1H, s, NH)
화합물 154: 1-(3-(3-Compound 154: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.57-1.65 (10H, m, Cycloheptyl), 1.96-2.00 (2H, m, Cycloheptyl), 3.98-4.03 (1H, m, Cycloheptyl), 5.38 (2H, s, OCH2Ph), 7.30-7.33 (4H, m, Ph+NH), 7.41 (1H, s, Ph), 7.62 (1H, d, J = 3.12 Hz, pyrazine), 7.68 (1H, d, J = 3.12 Hz, pyrazine), 9.05 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3) δ = 1.57-1.65 (10H, m, Cycloheptyl), 1.96-2.00 (2H, m, Cycloheptyl), 3.98-4.03 (1H, m, Cycloheptyl), 5.38 (2H, s , OCH 2 Ph), 7.30-7.33 ( 4H, m, Ph + NH), 7.41 (1H, s, Ph), 7.62 (1H, d, J = 3.12 Hz, pyrazine), 7.68 (1H, d, J = 3.12 Hz, pyrazine), 9.05 (1H, s, NH)
화합물 155: 1-(3-(3-Compound 155: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2,4,4-Pyrazin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.01 (9H, s, 3CH3), 1.48 (6H, s, 2CH3), 1.80 (2H, s, CH2), 5.37 (2H, s, OCH2Ph), 7.13 (1H, s, NH), 7.30-7.33 (3H, m, Ph), 7.41 (1H, s, Ph), 7.60 (1H, d, J = 3.12 Hz, pyrazine), 7.65 (1H, d, J = 3.12 Hz, pyrazine), 9.03 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.01 (9H, s, 3CH 3 ), 1.48 (6H, s, 2CH 3 ), 1.80 (2H, s, CH 2 ), 5.37 (2H, s, OCH 2 Ph), 7.13 (1H, s, NH), 7.30-7.33 (3H, m, Ph), 7.41 (1H, s, Ph), 7.60 (1H, d, J = 3.12 Hz, pyrazine), 7.65 (1H, d, J = 3.12 Hz, pyrazine), 9.03 (1H, s, NH)
화합물 156: 1-(3-(3-Compound 156: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-에틸 ) Pyrazin-2-yl) -3-ethyl 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 1.11 (3H, t, J = 7.2 Hz, CH3), 2.26-7.27 (2H, m, CH2), 5.42 (2H, s, OCH2Ph), 7.37-7.44 (2H, m, Ph), 7.46-7.48 (1H, m, Ph), 7.67 (1H, brs, Ph), 7.71 (1H, d, J = 3.0 Hz, pyrazine), 7.80 (1H, d, J = 3.0 Hz, Ph), 8.52 (1H, s, NH), 8.81 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 1.11 (3H, t, J = 7.2 Hz, CH 3 ), 2.26-7.27 (2H, m, CH 2 ), 5.42 (2H, s, OCH 2 Ph ), 7.37-7.44 (2H, m, Ph), 7.46-7.48 (1H, m, Ph), 7.67 (1H, brs, Ph), 7.71 (1H, d, J = 3.0 Hz, pyrazine), 7.80 (1H , d, J = 3.0 Hz, Ph), 8.52 (1H, s, NH), 8.81 (1H, s, NH)
화합물 157: 1-(3-(3-Compound 157: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 1.34 (9H, s, 3CH3), 5.49 (2H, s, OCH2Ph), 7.37-7.41 (2H, m, Ph), 7.43-7.48 (1H, m, Ph), 7.66 (1H, brs, Ph), 7.69 (1H, d, J = 3.0 Hz, Pyrazine), 7.79 (1H, d, J = 3.0 Hz, pyrazine), 8.26 (1H, s, NH), 8.82 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 1.34 (9H, s, 3CH 3 ), 5.49 (2H, s, OCH 2 Ph), 7.37-7.41 (2H, m, Ph), 7.43-7.48 ( 1H, m, Ph), 7.66 (1H, brs, Ph), 7.69 (1H, d, J = 3.0 Hz, Pyrazine), 7.79 (1H, d, J = 3.0 Hz, pyrazine), 8.26 (1H, s, NH), 8.82 (1H, s, NH)
화합물 158: 1-(3-(4-Compound 158: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 싸이클로헵틸Cycloheptyl 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 1.52-7.55 (10H, s, Cycloheptyl), 1.73-1.84 (2H, s, Cycloheptyl), 3.80-3.83 (1H, s, Cycloheptyl), 5.41 (2H, s, OCH2Ph), 7.44 (2H, d, J = 8.4 Hz, Ph), 7.56 (2H, d, J = 8.4 Hz, Ph), 7.70 (1H, d, J = 3.0 Hz, Py), 7.80 (1H, d, J = 3.0 Hz, Py), 8.40 (1H, s, NH), 8.90 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 1.52-7.55 (10H, s, Cycloheptyl), 1.73-1.84 (2H, s, Cycloheptyl), 3.80-3.83 (1H, s, Cycloheptyl), 5.41 (2H , s, OCH 2 Ph), 7.44 (2H, d, J = 8.4 Hz, Ph), 7.56 (2H, d, J = 8.4 Hz, Ph), 7.70 (1H, d, J = 3.0 Hz, Py), 7.80 (1H, d, J = 3.0 Hz, Py), 8.40 (1H, s, NH), 8.90 (1H, s, NH)
화합물 159: 1-(3-(4-Compound 159: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2,4,4-Pyrazin-2-yl) -3- (2,4,4- 트리메틸펜탄Trimethylpentane -2-일) -2 days) 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 0.96 (9H, s, 3CH3), 1.39 (6H, s, 2CH3), 1.73 (2H, s, CH2), 5.41 (2H, s, OCH2Ph), 7.45 (2H, d, J = 8.4 Hz, Ph), 7.57 (2H, d, J = 8.4 Hz, Ph), 7.69 (1H, d, J = 3.0 Hz, Py), 7.78 (1H, d, J = 3.0 Hz, Py), 8.12 (1H, s, NH), 8.91 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 0.96 (9H, s, 3CH 3 ), 1.39 (6H, s, 2CH 3 ), 1.73 (2H, s, CH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.45 (2H, d, J = 8.4 Hz, Ph), 7.57 (2H, d, J = 8.4 Hz, Ph), 7.69 (1H, d, J = 3.0 Hz, Py), 7.78 (1H , d, J = 3.0 Hz, Py), 8.12 (1H, s, NH), 8.91 (1H, s, NH)
화합물 160: 1-(3-(4-Compound 160: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-에틸 ) Pyrazin-2-yl) -3-ethyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.23 (3H, t, J = 7.2 Hz, CH3), 3.37-3.44 (2H, m, CH2), 5.38 (2H, s, OCH2Ph), 7.30 (1H, brs, NH), 7.36 (4H, brs, Ph), 7.62 (1H, d, J = 3.10 Hz, Pyrazine), 7.67 (1H, d, J = 3.10 Hz, pyrazine), 9.04 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.23 (3H, t, J = 7.2 Hz, CH 3 ), 3.37-3.44 (2H, m, CH 2 ), 5.38 (2H, s, OCH 2 Ph), 7.30 (1H, brs, NH), 7.36 (4H, brs, Ph), 7.62 (1H, d, J = 3.10 Hz, Pyrazine), 7.67 (1H, d, J = 3.10 Hz, pyrazine), 9.04 (1H, s, NH)
화합물 161: 1-(3-(4-Compound 161: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 삼차부틸Tert-butyl 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 1.42 (9H, s, 3CH3), 5.38 (2H, s, OCH2Ph), 7.15 (1H, brs, NH), 7.35 (4H, s, Ph), 7.59 (1H, d, J = 3.14 Hz, pyrazine), 7.66 (1H, d, J = 3.14 Hz, pyrazine), 8.99 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.42 (9H, s, 3CH 3 ), 5.38 (2H, s, OCH 2 Ph), 7.15 (1H, brs, NH), 7.35 (4H, s, Ph) , 7.59 (1H, d, J = 3.14 Hz, pyrazine), 7.66 (1H, d, J = 3.14 Hz, pyrazine), 8.99 (1H, s, NH)
실시예Example 6.1. 1-(3-( 6.1. 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
3-(3-벤질옥시)피라진-2-아민 (100 mg, 0.50 mmol)과 2-클로로에틸 아이소시아네이트 (50 μL, 0.60 mmol), DIPEA (0.26 mL, 1.50 mmol)를 테트라하이드로퓨란(0.25 M)에 녹인 후 15 시간 동안 가열 환류 시킨다. 반응 종결 후, 용매를 감압 농축하고, 잔여물을 컬럼크로마토그래피법 (초산에틸/노르말헥산 =1/2)으로 분리 정제하여 71.33%의 수율로 목적 화합물 109 mg을 얻었다.3- (3-benzyloxy) pyrazin-2-amine (100 mg, 0.50 mmol), 2-chloroethyl isocyanate (50 μL, 0.60 mmol), DIPEA (0.26 mL, 1.50 mmol) were added to tetrahydrofuran (0.25 M ) Is dissolved and heated to reflux for 15 hours. After completion of the reaction, the solvent was concentrated under reduced pressure, and the residue was separated and purified by column chromatography (ethyl acetate / normal hexane = 1/2) to obtain 109 mg of the target compound in a yield of 71.33%.
1H NMR (400 MHz, CDCl3) δ = 3.67-3.74 (4H, m, 2CH2), 5.41 (2H, s, OCH2Ph), 7.36-7.43 (6H, m, Ph+NH), 7.67 (1H, d, J = 3.08 Hz, pyrazine), 7.70 (1H, d, J = 3.08 Hz, pyrazine), 9.45 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.67-3.74 (4H, m, 2CH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.36-7.43 (6H, m, Ph + NH), 7.67 ( 1H, d, J = 3.08 Hz, pyrazine), 7.70 (1H, d, J = 3.08 Hz, pyrazine), 9.45 (1H, s, NH)
실시예Example 6.2. 1-(3-( 6.2. 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(2-(4-Pyrazin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) -1-yl) ethyl) 유레아Urea
수소화탄산칼륨 (41.1 mg, 0.49 mmol)과 1-메틸피페라진 (0.04 mL, 0.33 mmol)을 아세토니트릴 (3 mL)에 녹인 후, 1-(3-(벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아 (50 mg, 0.16 mmol)를 천천히 적가 한 후 20시간 동안 가열 환류시킨다. 반응물을 실온까지 식힌 후, 물을 넣는다. 혼합용액을 초산에틸로 추출한 후 황산나트륨으로 건조시키고, 감압 여과하여 감압 증류시킨다. 잔여물을 컬럼크로마토그래피법 (메틸렌클로라이드/메탄올 =1/1)으로 분리 정제하여 45.38%의 수율로 목적화합물 27.4 mg 얻었다.Potassium hydride (41.1 mg, 0.49 mmol) and 1-methylpiperazine (0.04 mL, 0.33 mmol) were dissolved in acetonitrile (3 mL), then 1- (3- (benzyloxy) pyrazin-2-yl)- 3- (2-chloroethyl) urea (50 mg, 0.16 mmol) was slowly added dropwise and heated to reflux for 20 hours. After the reaction has cooled to room temperature, water is added. The mixed solution was extracted with ethyl acetate, dried over sodium sulfate, filtered under reduced pressure and distilled under reduced pressure. The residue was separated and purified by column chromatography (methylene chloride / methanol = 1/1) to obtain 27.4 mg of the target compound in a yield of 45.38%.
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 2.48-2.60 (10H, m, 5CH2), 3.47-3.51 (2H, m, CH2), 5.41 (2H, s, OCH2Ph), 7.34-7.44 (6H, m, Ph+NH), 7.65 (1H, d, J = 3.08 Hz, pyrazine), 7.69 (1H, d, J = 3.08 Hz, pyrazine), 9.31 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 2.48-2.60 (10H, m, 5CH 2 ), 3.47-3.51 (2H, m, CH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.34-7.44 (6H, m, Ph + NH), 7.65 (1H, d, J = 3.08 Hz, pyrazine), 7.69 (1H, d, J = 3.08 Hz, pyrazine), 9.31 ( 1H, s, NH)
이하, 하기 화합물 162 내지 173을 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
Hereinafter, the following Compounds 162 to 173 were obtained by a similar method to the above Examples, and the analysis results of these compounds were as follows:
화합물 162: 1-(3-(Compound 162: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.67-3.74 (4H, m, 2CH2), 5.41 (2H, s, OCH2Ph), 7.36-7.43 (6H, m, Ph+NH), 7.67 (1H, d, J = 3.08 Hz, pyrazine), 7.70 (1H, d, J = 3.08 Hz, pyrazine), 9.45 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.67-3.74 (4H, m, 2CH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.36-7.43 (6H, m, Ph + NH), 7.67 ( 1H, d, J = 3.08 Hz, pyrazine), 7.70 (1H, d, J = 3.08 Hz, pyrazine), 9.45 (1H, s, NH)
화합물 163: 1-(3-(Compound 163: 1- (3- ( 벤질옥시Benzyloxy )피라진-2-일)-3-(2-(4-Pyrazin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) -1-yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.32 (3H, s, CH3), 2.48-2.60 (10H, m, 5CH2), 3.47-3.51 (2H, m, CH2), 5.41 (2H, s, OCH2Ph), 7.34-7.44 (6H, m, Ph+NH), 7.65 (1H, d, J = 3.08 Hz, pyrazine), 7.69 (1H, d, J = 3.08 Hz, pyrazine), 9.31 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.32 (3H, s, CH 3 ), 2.48-2.60 (10H, m, 5CH 2 ), 3.47-3.51 (2H, m, CH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.34-7.44 (6H, m, Ph + NH), 7.65 (1H, d, J = 3.08 Hz, pyrazine), 7.69 (1H, d, J = 3.08 Hz, pyrazine), 9.31 ( 1H, s, NH)
화합물 164: 1-(3-(3-Compound 164: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.67-3.75 (4H, m, 2CH2), 5.41 (2H, s, OCH2Ph), 7.03-7.08 (1H, m, Ph), 7.11-7.14 (1H, m, Ph), 7.20 (1H, d, J = 7.63 Hz, Ph), 7.33-7.39 (2H, m, Ph+NH), 7.67 (1H, d, J = 3.09 Hz, pyrazine), 7.70 (1H, d, J = 3.09 Hz, pyrazine), 9.44 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.67-3.75 (4H, m, 2CH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.03-7.08 (1H, m, Ph), 7.11-7.14 ( 1H, m, Ph), 7.20 (1H, d, J = 7.63 Hz, Ph), 7.33-7.39 (2H, m, Ph + NH), 7.67 (1H, d, J = 3.09 Hz, pyrazine), 7.70 ( 1H, d, J = 3.09 Hz, pyrazine), 9.44 (1H, s, NH)
화합물 165: 1-(3-(3-Compound 165: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(2-(4-Pyrazin-2-yl) -3- (2- (4- 메틸피페라Methylpipera 진-1-일)에틸) Jin-1-yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.31 (3H, s, CH3), 2.45-2.60 (10H, m, 5CH2), 3.47-3.51 (2H, m, CH2), 5.41 (2H, s, OCH2Ph), 7.04-7.06 (1H, m, Ph), 7.11-7.13 (1H, m, Ph), 7.20 (1H, d, J = 7.56 Hz, Ph), 7.33 (1H, s, NH), 7.34-7.36 (1H, m, Ph), 7.65 (1H, d, J = 3.07 Hz, pyrazine), 7.70 (1H, d, J = 3.09 Hz, pyrazine), 9.41 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.31 (3H, s, CH 3 ), 2.45-2.60 (10H, m, 5CH 2 ), 3.47-3.51 (2H, m, CH 2 ), 5.41 (2H, s, OCH 2 Ph), 7.04-7.06 (1H, m, Ph), 7.11-7.13 (1H, m, Ph), 7.20 (1H, d, J = 7.56 Hz, Ph), 7.33 (1H, s, NH ), 7.34-7.36 (1H, m, Ph), 7.65 (1H, d, J = 3.07 Hz, pyrazine), 7.70 (1H, d, J = 3.09 Hz, pyrazine), 9.41 (1H, s, NH)
화합물 166: 1-(3-(4-Compound 166: 1- (3- (4- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.68-3.73 (4H, m, 2CH2), 5.38 (2H, s, OCH2Ph), 7.08 (2H, t, J = 8.4 Hz, Ph), 7.36 (1H, brs, NH), 7.39-7.43 (2H, m, Ph), 7.67 (1H, d, J = 3.2 Hz, pyrazine), 7.71 (1H, d, J = 3.2 Hz, pyrazine), 9.44 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.68-3.73 (4H, m, 2CH 2 ), 5.38 (2H, s, OCH 2 Ph), 7.08 (2H, t, J = 8.4 Hz, Ph), 7.36 (1H, brs, NH), 7.39-7.43 (2H, m, Ph), 7.67 (1H, d, J = 3.2 Hz, pyrazine), 7.71 (1H, d, J = 3.2 Hz, pyrazine), 9.44 (1H , s, NH)
화합물 167: 1-(3-(2-Compound 167: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.67-3.75 (4H, m, 2CH2), 5.52 (2H, s, OCH2Ph), 7.27-7.35 (2H, m, Ph), 7.36 (1H, brs, NH), 7.43-7.46 (2H, m, Ph), 7.69 (1H, d, J = 3.09 Hz, pyrazine), 7.72 (1H, d, J = 3.09 Hz, pyrazine), 9.46 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.67-3.75 (4H, m, 2CH 2 ), 5.52 (2H, s, OCH 2 Ph), 7.27-7.35 (2H, m, Ph), 7.36 (1H, brs, NH), 7.43-7.46 (2H, m, Ph), 7.69 (1H, d, J = 3.09 Hz, pyrazine), 7.72 (1H, d, J = 3.09 Hz, pyrazine), 9.46 (1H, s, NH)
화합물 168: 1-(3-(2-Compound 168: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-(피페라진-1-일)에틸) Pyrazin-2-yl) -3- (2- (piperazin-1-yl) ethyl) 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 2.51-2.69 (12H, m, 6CH2), 5.50 (2H, s, OCH2Ph), 7.37-7.40 (2H, m, Ph), 7.44 (2H, d, J = 8.4 Hz, Ph), 7.57 (2H, d, J = 8.4 Hz, Ph), 7.69 (1H, d, J = 3.0 Hz, pyrazine), 7.78 (1H, d, J = 3.0 Hz, pyrazine), 8.11 (1H, s, NH), 8.91 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 2.51-2.69 (12H, m, 6CH 2 ), 5.50 (2H, s, OCH 2 Ph), 7.37-7.40 (2H, m, Ph), 7.44 ( 2H, d, J = 8.4 Hz, Ph), 7.57 (2H, d, J = 8.4 Hz, Ph), 7.69 (1H, d, J = 3.0 Hz, pyrazine), 7.78 (1H, d, J = 3.0 Hz , pyrazine), 8.11 (1H, s, NH), 8.91 (1H, s, NH)
화합물 169: 1-(3-(2-Compound 169: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-(4-Pyrazin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) -1-yl) ethyl) 유레아Urea
1H NMR (300 MHz, DMSO-d6) δ = 2.15 (3H, s, CH3), 2.31-3.43 (10H, m, 5CH2), 3.31-3.34 (2H, m, CH2), 5.50 (2H, s, OCH2Ph), 7.37-7.40 (2H, m, Ph), 7.49-7.54 (1H, m, Ph), 7.67-7.70 (1H, m, Ph), 7.75 (1H, d, J = 3.0 Hz, pyrazine), 7.80 (1H, d, J = 3.0 Hz, pyrazine), 8.38 (1H, s, NH), 9.08 (1H, s, NH)
1 H NMR (300 MHz, DMSO-d 6 ) δ = 2.15 (3H, s, CH 3 ), 2.31-3.43 (10H, m, 5CH 2 ), 3.31-3.34 (2H, m, CH 2 ), 5.50 ( 2H, s, OCH 2 Ph), 7.37-7.40 (2H, m, Ph), 7.49-7.54 (1H, m, Ph), 7.67-7.70 (1H, m, Ph), 7.75 (1H, d, J = 3.0 Hz, pyrazine), 7.80 (1H, d, J = 3.0 Hz, pyrazine), 8.38 (1H, s, NH), 9.08 (1H, s, NH)
화합물 170: 1-(3-(3-Compound 170: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.68-3.74 (4H, m, 2CH2), 5.39 (2H, s, OCH2Ph), 7.31-7.35 (4H, m, Ph+NH), 7.41 (1H, brs, Ph), 7.67 (1H, d, J = 3.09 Hz, pyrazine), 7.72 (1H, d, J = 3.09 Hz, pyrazine), 9.44 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.68-3.74 (4H, m, 2CH 2 ), 5.39 (2H, s, OCH 2 Ph), 7.31-7.35 (4H, m, Ph + NH), 7.41 ( 1H, brs, Ph), 7.67 (1H, d, J = 3.09 Hz, pyrazine), 7.72 (1H, d, J = 3.09 Hz, pyrazine), 9.44 (1H, s, NH)
화합물 171: 1-(3-(3-Compound 171: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-(피페라진-1-일)에틸) Pyrazin-2-yl) -3- (2- (piperazin-1-yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.49 (4H, brs, 2CH2), 2.56 (2H, t, J = 6.31 Hz, CH2), 2.93 (4H, t, J = 4.8 Hz, 2CH2), 3.47-3.51 (2H, m, CH2), 7.30-7.34 (4H, m, Ph+NH), 7.41 (1H, brs, Ph), 7.64 (1H, d, J = 3.08 Hz, pyrazine), 7.70 (1H, d, J = 3.08 Hz, pyrazine), 9.32 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.49 (4H, brs, 2CH 2 ), 2.56 (2H, t, J = 6.31 Hz, CH 2 ), 2.93 (4H, t, J = 4.8 Hz, 2CH 2 ), 3.47-3.51 (2H, m, CH 2 ), 7.30-7.34 (4H, m, Ph + NH), 7.41 (1H, brs, Ph), 7.64 (1H, d, J = 3.08 Hz, pyrazine), 7.70 (1H, doublet, J = 3.08 Hz, pyrazine), 9.32 (1H, s, NH)
화합물 172: 1-(3-(3-Compound 172: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-(4-Pyrazin-2-yl) -3- (2- (4- 메틸피페라진Methylpiperazine -1-일)에틸) -1-yl) ethyl) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 2.30 (3H, s, CH3), 2.32-2.61 (10H, m, 4CH2), 3.33-3.51 (4H, m, 2CH2), 5.39 (2H, s, OCH2Ph), 7.30-7.34 (4H, m, Ph+NH), 7.41 (1H, brs, Ph), 7.64 (1H, d, J = 3.06 Hz, pyrazine), 7.70 (1H, d, J = 3.06 Hz, pyrazine), 9.31 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.30 (3H, s, CH 3 ), 2.32-2.61 (10H, m, 4CH 2 ), 3.33-3.51 (4H, m, 2CH 2 ), 5.39 (2H, s, OCH 2 Ph), 7.30-7.34 (4H, m, Ph + NH), 7.41 (1H, brs, Ph), 7.64 (1H, d, J = 3.06 Hz, pyrazine), 7.70 (1H, d, J = 3.06 Hz, pyrazine), 9.31 (1H, s, NH)
화합물 173: 1-(3-(4-Compound 173: 1- (3- (4- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(2-Pyrazin-2-yl) -3- (2- 클로로에틸Chloroethyl ) ) 유레아Urea
1H NMR (400 MHz, CDCl3) δ = 3.68-3.74 (4H, m, 2CH2), 5.39 (2H, s, OCH2Ph), 7.36 (4H, s, Ph), 7.66 (1H, d, J = 2.98 Hz, pyrazine), 7.71 (1H, d, J = 2.98 Hz, pyrazine), 7.93 (1H, d, J = 2.62 Hz, NH), 9.48 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 3.68-3.74 (4H, m, 2CH 2 ), 5.39 (2H, s, OCH 2 Ph), 7.36 (4H, s, Ph), 7.66 (1H, d, J = 2.98 Hz, pyrazine), 7.71 (1H, d, J = 2.98 Hz, pyrazine), 7.93 (1H, d, J = 2.62 Hz, NH), 9.48 (1H, s, NH)
실시예Example 7.1. 1-(3- 7.1. 1- (3- 클로로페닐Chlorophenyl )-3-(3-) -3- (3- 하이드록시피리딘Hydroxypyridine -2-일)-2 days) 유레아Urea
질소 하에서 테트라하이드로퓨란 (4.5 mL)에 2-아미노-3-하이드록시피리딘 (100 mg, 0.91 mmol)을 용해시킨 후, 상온에서 3-클로로페닐이소시아네이트 (0.13 mL, 1.10 mmol)를 적가하고, 9 시간 동안 70 ℃에서 환류 교반시킨다. 반응이 종결된 후, 감압 증류하여 얻어진 혼합물은 디에틸에테르를 가하면 침전물이 생기고, 이 침전물을 여과하고 건조시켜 62% 수율로 목적화합물(148 mg, 0.56 mmol)을 얻었다.Dissolve 2-amino-3-hydroxypyridine (100 mg, 0.91 mmol) in tetrahydrofuran (4.5 mL) under nitrogen, then add dropwise 3-chlorophenylisocyanate (0.13 mL, 1.10 mmol) at room temperature, 9 Stir at reflux at 70 ° C. for time. After the reaction was completed, the mixture obtained by distillation under reduced pressure gave a precipitate when diethyl ether was added. The precipitate was filtered and dried to obtain the target compound (148 mg, 0.56 mmol) in 62% yield.
1H NMR (DMSO-d6, 300 MHz) d 11.78 (s, 1H), 10.67 (s, 1H), 7.85 (dd, J = 5.0, 1.4 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1H), 7.46-7.43 (m, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.21 (dd, J = 7.9, 1.4 Hz, 1H), 7.11-7.01 (m, 1H), 7.0 (dd, J = 7.9, 5.0 Hz, 1H)
1 H NMR (DMSO-d 6 , 300 MHz) d 11.78 (s, 1H), 10.67 (s, 1H), 7.85 (dd, J = 5.0, 1.4 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1H), 7.46-7.43 (m, 1H), 7.34 (t, J = 7.9 Hz, 1H), 7.21 (dd, J = 7.9, 1.4 Hz, 1H), 7.11-7.01 (m, 1H), 7.0 (dd , J = 7.9, 5.0 Hz, 1H)
실시예Example 7.2. 1-(3- 7.2. 1- (3- 클로로페닐Chlorophenyl )-3-(3-) -3- (3- 벤질옥시피리딘Benzyloxypyridine -2-일)-2 days) 유레아의Urea 정제 refine
1-(3-클로로페닐)-3-(3-벤질옥시피리딘-2-일)유레아 (50 mg, 0.14 mmol)를 메탄올 (3 mL)에 용해시킨 후, Pd(OH)2( 5.0 mg, 0.036 mmol)를 넣어준다. 혼합용액을 수소분위기 하에서 5 시간 동안 교반시킨다. 반응이 종결된 후, 반응 혼합용액은 셀라이트로 여과시킨 후, 여과액을 감압 증류하여, 100% 수율로 목적화합물 (38.9mg, 0.14 mmol)을 얻었다.
1- (3-chlorophenyl) -3- (3-benzyloxypyridin-2-yl) urea (50 mg, 0.14 mmol) was dissolved in methanol (3 mL), followed by Pd (OH) 2 (5.0 mg, 0.036 mmol). The mixed solution is stirred for 5 hours under a hydrogen atmosphere. After the reaction was completed, the reaction mixture was filtered through celite, and the filtrate was distilled under reduced pressure to obtain the target compound (38.9 mg, 0.14 mmol) in 100% yield.
실시예Example 7.3. 1-(3-(4- 7.3. 1- (3- (4- 니트로벤질옥시Nitrobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1-(3-클로로페닐)-3-(3-하이드록시피리딘-2-일)유레아 (100 mg, 0.65 mmol)를 아세토니트릴 (4.0 ml)에 용해시킨 후, 4-니트로벤질 브로마이드 (99 mg, 0.46 mmol)와 탄산칼륨 (78.77 mg, 0.57 mmol)를 상온에서 적가한 후, 10시간 동안 교반시킨다. 반응이 종결된 후, 물과 에틸아세테이트를 가하여 추출한 유기용매층을 염화나트륨 포화용액으로 세척한 후 황산마그네슘으로 건조시키고, 여과한 후 감압 증류한다. 혼합물에 디에틸에테르를 가한 후 얻어진 침전물을 여과하고 건조시켜 61% 수율로 목적화합물(91.78 mg, 0.23 mmol)을 얻었다. 1- (3-chlorophenyl) -3- (3-hydroxypyridin-2-yl) urea (100 mg, 0.65 mmol) was dissolved in acetonitrile (4.0 ml) and then 4-nitrobenzyl bromide (99 mg , 0.46 mmol) and potassium carbonate (78.77 mg, 0.57 mmol) were added dropwise at room temperature, followed by stirring for 10 hours. After the reaction was completed, the organic solvent layer extracted by adding water and ethyl acetate was washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and distilled under reduced pressure. Diethyl ether was added to the mixture, and the obtained precipitate was filtered and dried to obtain the target compound (91.78 mg, 0.23 mmol) in 61% yield.
1H NMR (DMSO-d6, 300 MHz) d 11.78 (s, 1H), 8.75 (s, 1H), 8.28 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 5.0, 1.1 Hz, 1H), 7.84 (dd, J = 6.8, 1.7 Hz, 3H), 7.53 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.13-7.06 (m, 2H), 5.44 (s, 2H)
1 H NMR (DMSO-d 6 , 300 MHz) d 11.78 (s, 1H), 8.75 (s, 1H), 8.28 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 5.0, 1.1 Hz, 1H), 7.84 (dd, J = 6.8, 1.7 Hz, 3H), 7.53 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.13-7.06 (m, 2H), 5.44 (s, 2H)
이하, 하기 화합물 174 내지 182를 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
The following compounds 174 to 182 were obtained by the same method as the above examples, and the analysis results of these compounds were as follows:
화합물 174: 1-(3-(2-Compound 174: 1- (3- (2- 니트로벤질옥시Nitrobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.76 (s, 1H), 8.66 (s, 1H), 8.19 (dd, J = 8.2, 1.0 Hz, 1H), 7.99 (dd, J = 5.1, 1.1 Hz, 1H), 7.87-7.78(m, 4H), 7.68-7.62 (m, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.47 (d, J = 9.1 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.12-7.05 (m, 2H), 5.62 (s, 2H); yield 38%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.76 (s, 1H), 8.66 (s, 1H), 8.19 (dd, J = 8.2, 1.0 Hz, 1H), 7.99 (dd, J = 5.1, 1.1 Hz, 1H), 7.87-7.78 (m, 4H), 7.68-7.62 (m, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.47 (d, J = 9.1 Hz, 1H), 7.36 (t , J = 8.0 Hz, 1H), 7.12-7.05 (m, 2H), 5.62 (s, 2H); yield 38%
화합물 175: 1-(3-(3-Compound 175: 1- (3- (3- 니트로벤질옥시Nitrobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.88 (s, 1H), 8.71 (s, 1H), 8.47 (s, 1H), 8.21 (d, J = 8.2 Hz, 1H), 8.04 (d, J = 7.6 Hz, 1H), 7.96 (d, J = 4.3 Hz, 1H), 7.83 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.55 (d, J = 7.7 Hz, 1H), 7.47 (d, J = 8.2 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.11-7.04 (m, 2H), 5.40 (s, 2H); yield 65%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.88 (s, 1H), 8.71 (s, 1H), 8.47 (s, 1H), 8.21 (d, J = 8.2 Hz, 1H), 8.04 (d, J = 7.6 Hz, 1H), 7.96 (d, J = 4.3 Hz, 1H), 7.83 (s, 1H), 7.71 (t, J = 7.9 Hz, 1H), 7.55 (d, J = 7.7 Hz, 1H) , 7.47 (d, J = 8.2 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.11-7.04 (m, 2H), 5.40 (s, 2H); yield 65%
화합물 176: 1-(3-(4-Compound 176: 1- (3- (4- 니트로벤질옥시Nitrobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.78 (s, 1H), 8.75 (s, 1H), 8.28 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 5.0, 1.1 Hz, 1H), 7.84 (dd, J = 6.8, 1.7 Hz, 3H), 7.53 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.13-7.06 (m, 2H), 5.44 (s, 2H); yield 61%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.78 (s, 1H), 8.75 (s, 1H), 8.28 (d, J = 8.8 Hz, 2H), 7.97 (dd, J = 5.0, 1.1 Hz, 1H), 7.84 (dd, J = 6.8, 1.7 Hz, 3H), 7.53 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.13-7.06 (m, 2H), 5.44 (s, 2H); yield 61%
화합물 177: 1-(3-(2-Compound 177: 1- (3- (2- 메틸벤질옥시Methylbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.66 (s, 1H), 8.41 (s, 1H), 7.96 (d, J = 4.9 Hz, 1H), 7.81 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 7.0 Hz, 2H), 7.37-7.22 (m, 4H), 7.12 (t, J = 8.0 Hz, 2H), 5.26 (s, 2H), 2.36 (s, 3H); yield 30%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.66 (s, 1H), 8.41 (s, 1H), 7.96 (d, J = 4.9 Hz, 1H), 7.81 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 7.0 Hz, 2H), 7.37-7.22 (m, 4H), 7.12 (t, J = 8.0 Hz, 2H), 5.26 (s, 2H), 2.36 ( s, 3H); yield 30%
화합물 178: 1-(3-(3-Compound 178: 1- (3- (3- 메틸벤질옥시Methylbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.26 (s, 1H), 7.95 (dd, J = 5.5, 1.1 Hz, 1H), 7.81 (d, J = 1.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.42-7.28 (m, 5H), 7.24-7.12 (m, 3H), 5.31 (s, 2H), 2.32 (s, 3H); yield 60%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.26 (s, 1H), 7.95 (dd, J = 5.5, 1.1 Hz, 1H), 7.81 (d, J = 1.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.42-7.28 (m, 5H), 7.24-7.12 (m, 3H), 5.31 (s, 2H), 2.32 (s, 3H); yield 60%
화합물 179: 1-(3-(3-Compound 179: 1- (3- (3- 메톡시벤질옥시Methoxybenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.76 (s, 1H), 8.48 (s, 1H), 7.94 (d, J = 4.4 Hz, 1H), 7.83 (s, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.46 (d, J = 8.3 Hz, 1H), 7.38-7.29 (m, 2H), 7.14-7.04 (m, 4H), 6.91 (dd, J = 7.9, 2.1 Hz, 1H), 5.24 (s, 2H), 3.37 (s, 3H); yield 40%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.76 (s, 1H), 8.48 (s, 1H), 7.94 (d, J = 4.4 Hz, 1H), 7.83 (s, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.46 (d, J = 8.3 Hz, 1H), 7.38-7.29 (m, 2H), 7.14-7.04 (m, 4H), 6.91 (dd, J = 7.9, 2.1 Hz, 1H ), 5.24 (s, 2 H), 3.37 (s, 3 H); yield 40%
화합물 180: 1-(3-(2-Compound 180: 1- (3- (2- 플루오로벤질옥시Fluorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.68 (s, 1H), 7.97 (dd, J= 5.2, 1.2 Hz, 1H), 7.81 (t, J = 2.0 Hz, 1H), 7.69-7.63 (m, 2H), 7.46-7.42 (m, 2H), 7.38-7.23 (m, 3H), 7.15-7.09 (m, 2H), 5.32 (s, 2H); yield 20%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.68 (s, 1H), 7.97 (dd, J = 5.2, 1.2 Hz, 1H), 7.81 (t, J = 2.0 Hz, 1H), 7.69-7.63 ( m, 2H), 7.46-7.42 (m, 2H), 7.38-7.23 (m, 3H), 7.15-7.09 (m, 2H), 5.32 (s, 2H); yield 20%
화합물 181: 1-(3-(3-Compound 181: 1- (3- (3- 플루오로벤질옥시Fluorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.66 (s, 1H), 8.74 (s, 1H), 7.95 (dd, J = 5.1, 1.2 Hz, 1H), 7.83 (t, J = 1.9 Hz, 1H), 7.57 (d, J = 8.3 Hz, 1H), 7.49-7.42 (m, 3H), 7.39-7.33 (m, 2H), 7.21-7.15 (m, 1H), 7.12-7.08 (m, 2H), 5.31 (s, 2H); yield 20%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.66 (s, 1H), 8.74 (s, 1H), 7.95 (dd, J = 5.1, 1.2 Hz, 1H), 7.83 (t, J = 1.9 Hz, 1H), 7.57 (d, J = 8.3 Hz, 1H), 7.49-7.42 (m, 3H), 7.39-7.33 (m, 2H), 7.21-7.15 (m, 1H), 7.12-7.08 (m, 2H) , 5.31 (s, 2 H); yield 20%
화합물 182: 1-(3-(4-Compound 182: 1- (3- (4- 플루오로벤질옥시Fluorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1H NMR (DMSO-d6, 300 MHz) d 11.46 (s, 1H), 8.46 (s, 1H), 7.95 (dd, J = 5.3, 1.0 Hz, 1H), 7.82 (t, J = 1.8 Hz, 1H), 7.68-7.59 (m, 3H), 7.44-7.33 (m, 2H), 7.25 (t, J = 8.9 Hz, 2H), 7.16-7.11 (m, 2H), 5.29 (s, 2H); yield 21%
1 H NMR (DMSO-d 6 , 300 MHz) d 11.46 (s, 1H), 8.46 (s, 1H), 7.95 (dd, J = 5.3, 1.0 Hz, 1H), 7.82 (t, J = 1.8 Hz, 1H), 7.68-7.59 (m, 3H), 7.44-7.33 (m, 2H), 7.25 (t, J = 8.9 Hz, 2H), 7.16-7.11 (m, 2H), 5.29 (s, 2H); yield 21%
실시예Example 8. 1-(3-(4- 8. 1- (3- (4- 메틸벤질옥시Methylbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
화합물 183: 1-(3-(4-Compound 183: 1- (3- (4- 메틸벤질옥시Methylbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1-(3-클로로페닐)-3-(3-하이드록시피리딘-2-일)유레아 (100 mg, 0.65 mmol)를 아세토니트릴 (4.0 ml)에 용해시킨 후, 4-메틸벤질 브로마이드 (99 mg, 0.46 mmol)와 탄산칼륨 (78.77 mg, 0.57 mmol)를 상온에서 적가하고, 10시간 동안 교반하였다. 반응이 종결된 후, 물과 에틸아세테이트를 가하여 추출한 유기용매층을 염화나트륨 포화용액으로 세척한 후 황산마그네슘으로 건조시키고, 여과한 후 감압 증류한다. 혼합물은 컬럼크로마토그래피법(SiO2, Hex : EtOAc = 3 : 1)으로 분리 정제하여 51% 수율로 목적화합물(142 mg, 0.39 mmol)을 얻었다.1- (3-chlorophenyl) -3- (3-hydroxypyridin-2-yl) urea (100 mg, 0.65 mmol) was dissolved in acetonitrile (4.0 ml) and then 4-methylbenzyl bromide (99 mg , 0.46 mmol) and potassium carbonate (78.77 mg, 0.57 mmol) were added dropwise at room temperature and stirred for 10 hours. After the reaction was completed, the organic solvent layer extracted by adding water and ethyl acetate was washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and distilled under reduced pressure. The mixture was separated and purified by column chromatography (SiO 2, Hex: EtOAc = 3: 1) in 51% yield. The target compound (142 mg, 0.39 mmol) was obtained.
1H NMR (DMSO-d6, 300 MHz) d 11.86 (s, 1H), 8.24 (s, 1H), 7.93 (dd, J = 5.0, 1.1 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1H), 7.51-7.41 (m, 4H), 7.34 (t, J = 8.0 Hz, 1H), 7.21 (d, J = 7.9 Hz, 2H), 7.10 (dd, J= 7.7, 1.2 Hz, 1H), 7.04 (m, 1H), 5.21 (s, 2H)
1 H NMR (DMSO-d 6 , 300 MHz) d 11.86 (s, 1H), 8.24 (s, 1H), 7.93 (dd, J = 5.0, 1.1 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1H), 7.51-7.41 (m, 4H), 7.34 (t, J = 8.0 Hz, 1H), 7.21 (d, J = 7.9 Hz, 2H), 7.10 (dd, J = 7.7, 1.2 Hz, 1H), 7.04 (m, 1 H), 5.21 (s, 2 H)
실시예Example 9. 1-(3-(4- 9. 1- (3- (4- 메톡시벤질옥시Methoxybenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
화합물 184: 1-(3-(4-Compound 184: 1- (3- (4- 메톡시벤질옥시Methoxybenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1-(3-클로로페닐)-3-(3-하이드록시피리딘-2-일)유레아 (100 mg, 0.65 mmol)를 아세토니트릴 (4.0 ml)에 용해시킨 후, 4-메톡시벤질 클로라이드 (99 mg, 0.46 mmol)와 탄산칼륨 (78.77 mg, 0.57 mmol), TBAI (56.15 mg, 0.15 mmol)를 상온에서 적가한 후, 10시간 동안 교반하였다. 반응이 종결된 후, 물과 에틸아세테이트를 가하여 추출한 유기용매층을 염화나트륨 포화용액으로 세척한 후 황산마그네슘으로 건조시키고, 여과한 후 감압 증류한다. 혼합물에 디에틸에테르를 가한 후 얻어진 침전물을 여과하고 건조시켜 89% 수율로 목적화합물(261 mg, 0.68 mmol)을 얻었다.1- (3-chlorophenyl) -3- (3-hydroxypyridin-2-yl) urea (100 mg, 0.65 mmol) was dissolved in acetonitrile (4.0 ml) and then 4-methoxybenzyl chloride (99 mg, 0.46 mmol), potassium carbonate (78.77 mg, 0.57 mmol) and TBAI (56.15 mg, 0.15 mmol) were added dropwise at room temperature, followed by stirring for 10 hours. After the reaction was completed, the organic solvent layer extracted by adding water and ethyl acetate was washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and distilled under reduced pressure. Diethyl ether was added to the mixture, and the obtained precipitate was filtered and dried to obtain the target compound (261 mg, 0.68 mmol) in 89% yield.
1H NMR (DMSO-d6, 300 MHz) d 11.87 (s, 1H), 8.20 (s, 1H), 7.93 (dd, J = 5.0, 1.2 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1 H), 7.52 (dd, J = 8.1, 1.3 Hz, 1H), 7.49-7.44 (m, 3H), 7.34 (t, J = 8.0, 1H), 7.12-7.08 (m, 1H), 7.04 (dd, J = 8.1, 5.0 Hz, 1H), 6.95 (dd, J = 6.7, 2.0 Hz, 2H), 5.18 (s, 2H), 3.75 (s, 3H)
1 H NMR (DMSO-d 6 , 300 MHz) d 11.87 (s, 1H), 8.20 (s, 1H), 7.93 (dd, J = 5.0, 1.2 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1 H), 7.52 (dd, J = 8.1, 1.3 Hz, 1H), 7.49-7.44 (m, 3H), 7.34 (t, J = 8.0, 1H), 7.12-7.08 (m, 1H), 7.04 (dd , J = 8.1, 5.0 Hz, 1H), 6.95 (dd, J = 6.7, 2.0 Hz, 2H), 5.18 (s, 2H), 3.75 (s, 3H)
실시예Example 10. 1-(3-(4- 10. 1- (3- (4- 플루오로벤질옥시Fluorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
화합물 185: 1-(3-(4-Compound 185: 1- (3- (4- 플루오로벤질옥시Fluorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 유레아Urea
1-(3-클로로페닐)-3-(3-하이드록시피리딘-2-일)유레아 (50 mg, 0.19 mmol)를 테트라하이드로퓨란 (2.0 mL)에 용해시킨 후, (2-메톡시페닐)메탄올 (0.023 mL, 0.19 mmol)과 PPh3(76.1 mg, 0.29 mmol)를 넣고, DIAD (0.11mL, 0.57 mmol)를 천천히 적가하였다. 반응용액을 상온에서 교반하였고, 반응이 종결된 후 반응용액은 감압 증류하였고, 혼합물은 관크로마토그래피법 (SiO2, Hex : EtOAc = 3 : 1)으로 분리정제하여 70% 수율로 목적화합물(51 mg, 0.13 mmol)을 얻었다.Dissolve 1- (3-chlorophenyl) -3- (3-hydroxypyridin-2-yl) urea (50 mg, 0.19 mmol) in tetrahydrofuran (2.0 mL) and then (2-methoxyphenyl) Methanol (0.023 mL, 0.19 mmol) and PPh3 (76.1 mg, 0.29 mmol) were added, and DIAD (0.11 mL, 0.57 mmol) was slowly added dropwise. The reaction solution was stirred at room temperature, and after completion of the reaction, the reaction solution was distilled under reduced pressure, and the mixture was purified by column chromatography (SiO 2, Hex: EtOAc = 3: 1) to obtain the target compound (51 mg) in 70% yield. , 0.13 mmol).
1H NMR (DMSO-d6, 300 MHz) d 11.86 (s, 1H), 8.13 (s, 1H), 7.97 (dd, J = 5.1, 1.2 Hz, 1H), 7.83 (t, J = 2.0 Hz, 1H), 7.55 (dd, J = 8.1, 1.2 Hz, 1H), 7.48-7.44(m, 2H), 7.37-7.32 (m, 2H), 7.12-7.04 (m, 3H), 7.00 (t, J = 6.9 Hz, 1H), 5.20 (s, 2H), 3.87 (s, 3H)
1 H NMR (DMSO-d 6 , 300 MHz) d 11.86 (s, 1H), 8.13 (s, 1H), 7.97 (dd, J = 5.1, 1.2 Hz, 1H), 7.83 (t, J = 2.0 Hz, 1H), 7.55 (dd, J = 8.1, 1.2 Hz, 1H), 7.48-7.44 (m, 2H), 7.37-7.32 (m, 2H), 7.12-7.04 (m, 3H), 7.00 (t, J = 6.9 Hz, 1H), 5.20 (s, 2H), 3.87 (s, 3H)
이하, 하기 화합물 186 내지 187을 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
Hereinafter, the following Compounds 186 to 187 were obtained by a method similar to the above Example, and the analysis results of these compounds were as follows:
화합물 186: 1-(3-(2,4-Compound 186: 1- (3- (2,4- 다이메톡시벤질옥시Dimethoxybenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) 유레아) Urea
1H NMR (DMSO-d6, 300 MHz) d 11.87(s, 1H), 7.99 (s, 1H), 7.96 (d, J = 5.0 Hz, 1H), 7.82 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.3 Hz, 1H), 7.34 (t, J = 8.0 Hz, 2H), 7.12-7.04 (m, 2H), 6.63 (d, J = 2.0 Hz, 1H), 6.53 (dd, J = 8.3, 2.2 Hz, 1H), 5.10 (s, 2H), 3.86 (s, 3H), 3.78 (d, J = 7.5 Hz, 3H)
1 H NMR (DMSO-d 6 , 300 MHz) d 11.87 (s, 1H), 7.99 (s, 1H), 7.96 (d, J = 5.0 Hz, 1H), 7.82 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.3 Hz, 1H), 7.34 (t, J = 8.0 Hz, 2H), 7.12-7.04 (m, 2H), 6.63 (d, J = 2.0 Hz, 1H), 6.53 (dd, J = 8.3, 2.2 Hz, 1H), 5.10 (s, 2H), 3.86 (s, 3H), 3.78 (d, J = 7.5 Hz, 3H)
화합물 187: 1-(3-(3,4-Compound 187: 1- (3- (3,4- 다이메톡시벤질옥시Dimethoxybenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) 유레아) Urea
1H NMR (DMSO-d6, 300 MHz) d 11.84 (s, 1H), 8.27 (s, 1H), 7.93(dd, J = 5.0, 1.2 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1H), 7.53 (dd, J = 8.1, 1.3 Hz, 1H), 7.45-7.44 (m, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.18 (d, J = 1.8Hz, 1H), 7.11-7.02 (m, 3H), 6.94 (d, J = 8.2 Hz, 1H), 5.16 (s, 2H), 3.75(d, J = 3.6 Hz, 6H)
1 H NMR (DMSO-d 6 , 300 MHz) d 11.84 (s, 1H), 8.27 (s, 1H), 7.93 (dd, J = 5.0, 1.2 Hz, 1H), 7.82 (t, J = 2.0 Hz, 1H), 7.53 (dd, J = 8.1, 1.3 Hz, 1H), 7.45-7.44 (m, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.18 (d, J = 1.8 Hz, 1H), 7.11-7.02 (m, 3H), 6.94 (d, J = 8.2 Hz, 1H), 5.16 (s, 2H), 3.75 (d, J = 3.6 Hz, 6H)
실시예 11. 1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아Example 11. 1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-isopropyl thiourea
수소화 나트륨 (60% in mineral oil, 34 mg, 0.85 mmol)과 3-(2-클로로벤질옥시)피리딘-2-아민 (100 mg, 0.43 mmol)을 테트라하이드로퓨란 (0.25M)에 녹인 후 이소프로필 티오아이소시아네이트 (0.06 mL, 0.51 mmol)을 천천히 적가 한 후 3시간 동안 가열 환류시킨다. 반응물을 실온까지 식힌 후, 물을 적가한 다음, 혼합 용액을 초산에틸로 추출한다. 유기층을 황산마그네슘으로 건조 후 감압 필터 하여 감압 농축한다. 잔여물을 소량의 디에틸에테르로 씻어준 후 감압 필터하여 72.3%의 수율로 목적 화합물 103.4 mg을 얻었다.Sodium hydride (60% in mineral oil, 34 mg, 0.85 mmol) and 3- (2-chlorobenzyloxy) pyridin-2-amine (100 mg, 0.43 mmol) are dissolved in tetrahydrofuran (0.25M) and isopropyl Thioisocyanate (0.06 mL, 0.51 mmol) is slowly added dropwise and then heated to reflux for 3 hours. After the reaction was cooled to room temperature, water was added dropwise, and the mixed solution was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under a reduced pressure filter. The residue was washed with a small amount of diethyl ether and filtered under reduced pressure to obtain 103.4 mg of the target compound in a yield of 72.3%.
1H NMR (400 MHz, CDCl3) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH3), 4.55-4.60 (1H, m, Ph), 5.55 (2H, s, OCH2Ph), 7.28-7.32 (2H, m, Ph), 7.42-7.45 (2H, m, Ph), 7.69 (1H, d, J = 3.2 Hz, pyrazine), 7.70 (1H, d, J = 3.2 Hz, pyrazine), 8.40 (1H, s, NH), 11.06 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH 3 ), 4.55-4.60 (1H, m, Ph), 5.55 (2H, s, OCH 2 Ph), 7.28 -7.32 (2H, m, Ph), 7.42-7.45 (2H, m, Ph), 7.69 (1H, d, J = 3.2 Hz, pyrazine), 7.70 (1H, d, J = 3.2 Hz, pyrazine), 8.40 (1H, s, NH), 11.06 (1H, s, NH)
이하, 하기 화합물 188 내지 222를 상기 실시예와 유사한 방법으로 수행하여 얻었으며, 이들 화합물의 분석결과는 다음과 같다:
Hereinafter, the following Compounds 188 to 222 were obtained by a method similar to the above Example, and the analysis results of these compounds were as follows:
화합물 188: 1-(3-(Compound 188: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.34 (3H, t, CH3), 3.75-3.82 (2H, m, CH2), 6.85 (1H, dd, J1 = 5.1 Hz, J2 = 8.07 Hz, Py), 7.11 (1H, dd, J1 = 1.30 Hz, J2 = 8.07 Hz, Py), 7.35-7.42 (5H, m, Ph), 7.75 (1H, dd, J1 = 5.1 Hz, J2 = 1.30 Hz, Py), 8.58 (1H, s, NH), 11.59 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.34 (3H, t, CH 3 ), 3.75-3.82 (2H, m, CH 2 ), 6.85 (1H, dd, J 1 = 5.1 Hz, J 2 = 8.07 Hz, Py), 7.11 (1H, dd, J 1 = 1.30 Hz, J 2 = 8.07 Hz, Py), 7.35-7.42 (5H, m, Ph), 7.75 (1H, dd, J 1 = 5.1 Hz, J 2 = 1.30 Hz, Py), 8.58 (1H, s, NH), 11.59 (1H, s, NH)
화합물 189: 1-(3-(Compound 189: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-이소프로필 Pyridin-2-yl) -3-isopropyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.35 (6H, d, J = 6.56 Hz, 2CH3), 4.59-4.60 (1H, m, CH), 5.15 (2H, s, OCH2Ph), 6.85 (1H, dd, J1 = 5.1 Hz, J2 = 8.07 Hz, Py), 7.11 (1H, dd, J1 = 1.30 Hz, J2 = 8.07 Hz, Py), 7.35-7.42 (5H, m, Ph), 7.75 (1H, dd, J1 = 1.30 Hz, J2 = 5.10 Hz, Py), 8.52 (1H, s, NH), 11.55 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.35 (6H, d, J = 6.56 Hz, 2CH 3 ), 4.59-4.60 (1H, m, CH), 5.15 (2H, s, OCH 2 Ph), 6.85 (1H, dd, J 1 = 5.1 Hz, J 2 = 8.07 Hz, Py), 7.11 (1H, dd, J 1 = 1.30 Hz, J 2 = 8.07 Hz, Py), 7.35-7.42 (5H, m, Ph), 7.75 (1H, dd, J 1 = 1.30 Hz, J 2 = 5.10 Hz, Py), 8.52 (1H, s, NH), 11.55 (1H, s, NH)
화합물 190: 1-(3-(Compound 190: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.63 (9H, s, 3CH3), 5.15 (2H, s, OCH2Ph), 6.82 (1H, dd, J1 = 5.09 Hz, J2 = 8.04 Hz, Py), 7.08 (1H, dd, J1 = 1.13 Hz, J2 = 8.04 Hz, Py), 7.34-7.41 (5H, m, Ph), 7.72 (1H, dd, J1 = 1.13 Hz, J2 = 5.09 Hz, Py), 8.43 (1H, s, NH), 11.82 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.63 (9H, s, 3CH 3 ), 5.15 (2H, s, OCH 2 Ph), 6.82 (1H, dd, J 1 = 5.09 Hz, J 2 = 8.04 Hz, Py), 7.08 (1H, dd, J 1 = 1.13 Hz, J 2 = 8.04 Hz, Py), 7.34-7.41 (5H, m, Ph), 7.72 (1H, dd, J 1 = 1.13 Hz, J 2 = 5.09 Hz, Py), 8.43 (1H, s, NH), 11.82 (1H, s, NH)
화합물 191: 1-(3-(Compound 191: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-벤질 ) Pyridin-2-yl) -3-benzyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.02 (2H, d, J = 5.6 Hz, OCH2Ph), 5.16 (2H, s, OCH2Ph), 6.84 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.11 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.29-7.30 (1H, m, Ph), 7.34-7.42 (9H, m, Ph), 7.67 (1H, dd, J1 = 5.2 Hz, J2 = 8.0 Hz, Py), 8.69 (1H, s, NH), 12.04 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.02 (2H, d, J = 5.6 Hz, OCH 2 Ph), 5.16 (2H, s, OCH 2 Ph), 6.84 (1H, dd, J 1 = 8.0 Hz , J 2 = 5.2 Hz, Py), 7.11 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.29-7.30 (1H, m, Ph), 7.34-7.42 (9H, m, Ph), 7.67 (1H, dd, J 1 = 5.2 Hz, J 2 = 8.0 Hz, Py), 8.69 (1H, s, NH), 12.04 (1H, s, NH)
화합물 192: 1-(3-(Compound 192: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 2.36 (3H, s, CH3), 5.18 (2H, s, OCH2Ph), 6.91 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.16 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.20 (2H, d, J = 8.0 Hz, Ph), 7.36-7.43 (5H, m, Ph), 7.54 (2H, d, J = 8.0 Hz, Ph), 7.80 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.73 (1H, s, NH), 13.47 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.36 (3H, s, CH 3 ), 5.18 (2H, s, OCH 2 Ph), 6.91 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz , Py), 7.16 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.20 (2H, d, J = 8.0 Hz, Ph), 7.36-7.43 (5H, m, Ph), 7.54 (2H, d, J = 8.0 Hz, Ph), 7.80 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.73 (1H, s, NH), 13.47 (1H, s, NH)
화합물 193: 1-(3-(Compound 193: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.19 (2H, s, OCH2Ph), 6.94 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.18-7.22 (2H, m, Ph+Py), 7.32 (1H, t, J = 8.0 Hz, Ph), 7.37-7.42 (5H, m, Ph), 7.66 (1H, d, J = 8.0 Hz, Ph), 7.79 (1H, t, J = 2.0 Hz, Ph), 7.81 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.76 (1H, s, NH), 13.73 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.19 (2H, s, OCH 2 Ph), 6.94 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.18-7.22 (2H, m, Ph + Py), 7.32 (1H, t, J = 8.0 Hz, Ph), 7.37-7.42 (5H, m, Ph), 7.66 (1H, d , J = 8.0 Hz, Ph), 7.79 (1H, t, J = 2.0 Hz, Ph), 7.81 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.76 (1H, s, NH), 13.73 (1H, s, NH)
화합물 194: 1-(3-(Compound 194: 1- (3- ( 벤질옥시Benzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.19 (2H, s, OCH2Ph), 6.96 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.22 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.36-7.44 (5H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.56 (1H, d, J = 7.6 Hz, Ph), 7.81-7.83 (2H, m, Ph+Py), 7.89-7.91 (1H, m, Ph), 8.00 (1H, d, J = 7.6 Hz, Ph), 8.07-8.09 (1H, m, Ph), 8.92 (1H, s, NH), 13.79 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.19 (2H, s, OCH 2 Ph), 6.96 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.22 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.36-7.44 (5H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.56 (1H, d, J = 7.6 Hz, Ph) , 7.81-7.83 (2H, m, Ph + Py), 7.89-7.91 (1H, m, Ph), 8.00 (1H, d, J = 7.6 Hz, Ph), 8.07-8.09 (1H, m, Ph), 8.92 (1H, s, NH), 13.79 (1H, s, NH)
화합물 195: 1-(3-(3-Compound 195: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.34 (3H, t, J = 7.2 Hz, CH3), 3.75-3.82 (2H, m, CH2), 5.14 (2H, s, OCH2Ph), 6.86 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.03-7.09 (3H, m, Ph+Py), 7.17 (1H, d, J = 7.2 Hz, Ph), 7.35-7.40 (1H, m, Ph), 7.77 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.56 (1H, s, NH), 11.56 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.34 (3H, t, J = 7.2 Hz, CH 3 ), 3.75-3.82 (2H, m, CH 2 ), 5.14 (2H, s, OCH 2 Ph), 6.86 (1H, doublet of doublets, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.03-7.09 (3H, m, Ph + Py), 7.17 (1H, d, J = 7.2 Hz, Ph), 7.35-7.40 (1H, m, Ph), 7.77 (1H, dd , J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.56 (1H, s, NH), 11.56 (1H, s, NH)
화합물 196: 1-(3-(3-Compound 196: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-이소프로필 Pyridin-2-yl) -3-isopropyl 티오유레아Thiourea ;;
1H NMR (400 MHz, CDCl3) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH3), 4.57-4.61 (1H, m, CH), 5.14 (2H, s, OCH2Ph), 6.85 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.05-7.08 (3H, m, Ph+Py), 7.16 (1H, d, J = 7.6 Hz, Ph), 7.35-7.39 (1H, m, Ph), 7.77 (1H, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.50 (1H, s, NH), 11.53 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH 3 ), 4.57-4.61 (1H, m, CH), 5.14 (2H, s, OCH 2 Ph), 6.85 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.05-7.08 (3H, m, Ph + Py), 7.16 (1H, d, J = 7.6 Hz, Ph), 7.35-7.39 (1H, m, Ph), 7.77 (1H, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.50 (1H, s, NH), 11.53 (1H, s, NH)
화합물 197: 1-(3-(3-Compound 197: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.63 (9H, s, 3CH3), 5.14 (2H, s, OCH2Ph), 6.82 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.03-7.08 (3H, m, Ph+Py), 7.16 (1H, J = 8.0 Hz, Ph), 7.34-7.39 (1H, m, Ph), 7.74 (1H, dd, J1 = 5.2 Hz, J2 = 1.6 Hz, Py), 8.40 (1H, s, NH), 11.80 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3) δ = 1.63 (9H, s, 3CH 3), 5.14 (2H, s, OCH 2 Ph), 6.82 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.03-7.08 (3H, m, Ph + Py), 7.16 (1H, J = 8.0 Hz, Ph), 7.34-7.39 (1H, m, Ph), 7.74 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.6 Hz, Py), 8.40 (1H, s, NH), 11.80 (1H, s, NH)
화합물 198: 1-(3-(3-Compound 198: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-벤질 ) Pyridin-2-yl) -3-benzyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.01 (2H, d, J = 5.6 Hz, OCH2Ph), 5.15 (2H, s, OCH2Ph), 6.85 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.04-7.10 (3H, m, Ph), 7.18 (1H, d, J = 7.6 Hz, Ph), 7.27-7.31 (1H, m, Ph), 7.34-7.42 (5H, m, Ph), 7.69 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.66 (1H, s, NH), 12.02 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.01 (2H, d, J = 5.6 Hz, OCH 2 Ph), 5.15 (2H, s, OCH 2 Ph), 6.85 (1H, dd, J 1 = 8.0 Hz , J 2 = 5.2 Hz, Py), 7.04-7.10 (3H, m, Ph), 7.18 (1H, d, J = 7.6 Hz, Ph), 7.27-7.31 (1H, m, Ph), 7.34-7.42 (5H, m , Ph), 7.69 (1H, doublet of doublets, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.66 (1H, s, NH), 12.02 (1H, s, NH)
화합물 199: 1-(3-(3-Compound 199: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 2.36 (3H, s, CH3), 5.17 (2H, s, OCH2Ph), 6.92 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.07-7.14 (3H, m, Ph), 7.18-7.19 (1H, m, Ph), 7.21 (2H, d, J = 8.0 Hz, Ph), 7.38-7.40 (1H, m, Ph), 7.54 (2H, d, J = 8.0 Hz, Ph), 7.82 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.71 (1H, s, NH), 13.45 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.36 (3H, s, CH 3 ), 5.17 (2H, s, OCH 2 Ph), 6.92 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz , Py), 7.07-7.14 (3H, m, Ph), 7.18-7.19 (1H, m, Ph), 7.21 (2H, d, J = 8.0 Hz, Ph), 7.38-7.40 (1H, m, Ph) , 7.54 (2H, d, J = 8.0 Hz, Ph), 7.82 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.71 (1H, s, NH), 13.45 (1H, s , NH)
화합물 200: 1-(3-(3-Compound 200: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.19 (2H, s, OCH2Ph), 6.94 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.07-7.11 (2H, m, Ph), 7.15 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.18-7.23 (2H, m, Ph), 7.33 (1H, t, J = 8.0 Hz, Ph), 7.37-7.42 (1H, m, Ph), 7.66 (1H, d, J = 8.0 Hz, Ph), 7.79 (1H, t, J = 2.0 Hz, Ph), 7.83 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.74 (1H, s, NH), 13.70 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.19 (2H, s, OCH 2 Ph), 6.94 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.07-7.11 (2H, m, Ph), 7.15 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.18-7.23 (2H, m, Ph), 7.33 (1H, t, J = 8.0 Hz, Ph), 7.37-7.42 (1H, m, Ph), 7.66 (1H, d, J = 8.0 Hz, Ph), 7.79 (1H, t, J = 2.0 Hz, Ph), 7.83 (1H, doublet of doublets, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.74 (1H, s, NH), 13.70 (1H, s, NH)
화합물 201: 1-(3-(3-Compound 201: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.21 (2H, s, OCH2Ph), 6.96 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.08-7.09(1H, m, Ph), 7.10-7.14 (1H, m, Ph), 7.18 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.22 (1H, d, J = 7.6 Hz, Ph), 7.38-7.44 (1H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.57 (1H, d, J = 8.0 Hz, Ph), 7.81-7.85 (2H, m, Ph+Py), 7.89-7.91 (1H, m, Ph), 8.00 (1H, d, J = 7.6 Hz, Ph), 8.07-8.09 (1H, m, Ph), 8.90 (1H, s, NH), 13.76 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.21 (2H, s, OCH 2 Ph), 6.96 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.08-7.09 (1H, m, Ph), 7.10-7.14 (1H, m, Ph), 7.18 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.22 (1H, d, J = 7.6 Hz, Ph) , 7.38-7.44 (1H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.57 (1H, d, J = 8.0 Hz, Ph), 7.81-7.85 (2H, m, Ph + Py), 7.89-7.91 (1H, m, Ph), 8.00 (1H, d, J = 7.6 Hz, Ph), 8.07-8.09 (1H, m, Ph), 8.90 (1H, s, NH), 13.76 (1H, s , NH)
화합물 202: 1-(3-(2-Compound 202: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.34 (3H, t, J = 7.6 Hz, CH3), 3.75-3.82 (2H, m, CH2), 5.25 (2H, s, OCH2Ph), 6.88 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.12 (1H, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.28-7.33 (2H, m, Ph), 7.41-7.44 (2H, m, Ph), 7.78 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.59 (1H, s, NH), 11.58 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.34 (3H, t, J = 7.6 Hz, CH 3 ), 3.75-3.82 (2H, m, CH 2 ), 5.25 (2H, s, OCH 2 Ph), 6.88 (1H, doublet of doublets, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.12 (1H, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.28-7.33 (2H, m, Ph), 7.41-7.44 (2H, m, Ph), 7.78 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.59 (1H, s, NH), 11.58 (1H, s, NH)
화합물 203: 1-(3-(2-Compound 203: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-이소프로필 Pyridin-2-yl) -3-isopropyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.36 (6H, d, J = 6.8 Hz, 2CH3), 4.57-4.63 (1H, m, CH), 5.25 (2H, s, OCH2Ph), 6.87 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.11 (1H, d, J = 8.0 Hz, Py), 7.29-7.33 (2H, m, Ph), 7.41-7.44 (2H, m, Ph), 7.78 (1H, d, J = 5.2 Hz, Py), 8.53 (1H, s, NH), 11.54 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.36 (6H, d, J = 6.8 Hz, 2CH 3 ), 4.57-4.63 (1H, m, CH), 5.25 (2H, s, OCH 2 Ph), 6.87 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.11 (1H, d, J = 8.0 Hz, Py), 7.29-7.33 (2H, m, Ph), 7.41-7.44 (2H , m, Ph), 7.78 (1H, d, J = 5.2 Hz, Py), 8.53 (1H, s, NH), 11.54 (1H, s, NH)
화합물 204: 1-(3-(2-Compound 204: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 티오유레아Thiourea
H NMR (400 MHz, CDCl3) δ = 1.63 (9H, s, 3CH3), 5.24 (2H, s, OCH2Ph), 6.85 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.09 (1H, J1 = 8.0 Hz, J2 = 1.2 Ph), 7.27-7.30 (2H, m, Ph), 7.40-7.43 (2H, m, Ph), 7.74 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.42 (1H, s, NH), 11.82 (1H, s, NH)
H NMR (400 MHz, CDCl 3 ) δ = 1.63 (9H, s, 3CH 3 ), 5.24 (2H, s, OCH 2 Ph), 6.85 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.09 (1H, J 1 = 8.0 Hz, J 2 = 1.2 Ph), 7.27-7.30 (2H, m, Ph), 7.40-7.43 (2H, m, Ph ), 7.74 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.42 (1H, s, NH), 11.82 (1H, s, NH)
화합물 205: 1-(3-(2-Compound 205: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 2.36 (3H, s, CH3), 5.29 (2H, s, OCH2Ph), 6.92 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.07-7.14 (3H, m, Ph), 7.18-7.19 (1H, m, Ph), 7.21 (2H, d, J = 8.0 Hz, Ph), 7.38-7.40 (1H, m, Ph), 7.54 (2H, d, J = 8.0 Hz, Ph), 7.82 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.74 (1H, s, NH), 13.47 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.36 (3H, s, CH 3 ), 5.29 (2H, s, OCH 2 Ph), 6.92 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.07-7.14 (3H, m, Ph), 7.18-7.19 (1H, m, Ph), 7.21 (2H, d, J = 8.0 Hz, Ph), 7.38-7.40 (1H, m , Ph), 7.54 (2H, d, J = 8.0 Hz, Ph), 7.82 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.74 (1H, s, NH), 13.47 (1H, s, NH)
화합물 206: 1-(3-(2-Compound 206: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.29 (2H, s, OCH2Ph), 6.94 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.10-7.12 (1H, m, Ph), 7.19-7.24 (2H, m, Ph), 7.28-7.35 (3H, m, Ph), 7.43-7.46 (2H, m, Ph), 7.66 (1H, d, J = 8.0 Hz, Ph), 7.78 (1H, t, J = 2.4 Hz, Ph), 7.85 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.76 (1H, s, NH), 13.72 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.29 (2H, s, OCH 2 Ph), 6.94 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.10-7.12 (1H, m, Ph), 7.19-7.24 (2H, m, Ph), 7.28-7.35 (3H, m, Ph), 7.43-7.46 (2H, m, Ph), 7.66 (1H, d, J = 8.0 Hz, Ph ), 7.78 (1H, t, J = 2.4 Hz, Ph), 7.85 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.76 (1H, s, NH), 13.72 (1H, s, NH)
화합물 207: 1-(3-(2-Compound 207: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.33 (2H, s, OCH2Ph), 6.96 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.22-7.25 (2H, m, Ph), 7.34-7.35 (2H, m, Ph), 7.43-7.49 (2H, m, Ph), 7.50-7.58 (3H, m, Ph+Py), 7.82( 1H, d, J = 8.0 Hz, Ph), 7.86 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 7.89-7.91 (1H, m, Ph), 8.0 (1H, d, J = 6.0 Hz, Ph), 8.07-8.10 (1H, m, Ph), 8.92 (1H, s, NH), 13.78 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.33 (2H, s, OCH 2 Ph), 6.96 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.22-7.25 (2H, m, Ph), 7.34-7.35 (2H, m, Ph), 7.43-7.49 (2H, m, Ph), 7.50-7.58 (3H, m, Ph + Py), 7.82 (1H, d, J = 8.0 Hz, Ph), 7.86 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 7.89-7.91 (1H, m, Ph), 8.0 (1H, d, J = 6.0 Hz, Ph), 8.07-8.10 (1H, m, Ph), 8.92 (1H, s, NH), 13.78 (1H, s, NH)
화합물 208: 1-(3-(3-Compound 208: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-에틸 Pyridin-2-yl) -3-ethyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.34 (3H, t, J = 7.2 Hz, CH3), 3.77-3.80 (2H, m, CH2), 5.12 (2H, s, OCH2Ph), 6.84-6.88 (1H, m, Py), 7.07 (1H, d, J = 8.0 Hz, Ph), 7.28 (1H, m, Ph), 7.34-7.36 (3H, m, Ph+Py), 7.77 (1H, d, J = 4.0 Hz, Py), 8.55 (1H, s, NH), 11.57 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.34 (3H, t, J = 7.2 Hz, CH 3 ), 3.77-3.80 (2H, m, CH 2 ), 5.12 (2H, s, OCH 2 Ph), 6.84-6.88 (1H, m, Py), 7.07 (1H, d, J = 8.0 Hz, Ph), 7.28 (1H, m, Ph), 7.34-7.36 (3H, m, Ph + Py), 7.77 (1H , d, J = 4.0 Hz, Py), 8.55 (1H, s, NH), 11.57 (1H, s, NH)
화합물 209: 1-(3-(3-Compound 209: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-이소프로필 Pyridin-2-yl) -3-isopropyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH3), 4.59-4.61 (1H, m, CH), 5.12 (2H, s, OCH2Ph), 6.85 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.06 (1H, d, J = 8.0 Hz, Py), 7.27 (1H, m, Ph), 7.33-7.35 (3H, m, Ph), 7.77 (1H, d, J = 5.2 Hz, Py), 8.49 (1H, s, NH), 11.53 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH 3 ), 4.59-4.61 (1H, m, CH), 5.12 (2H, s, OCH 2 Ph), 6.85 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.06 (1H, d, J = 8.0 Hz, Py), 7.27 (1H, m, Ph), 7.33-7.35 (3H, m, Ph), 7.77 (1H , d, J = 5.2 Hz, Py), 8.49 (1H, s, NH), 11.53 (1H, s, NH)
화합물 210: 1-(3-(3-Compound 210: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-Pyridin-2-yl) -3- 삼차부틸Tert-butyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.63 (9H, s, 3CH3), 5.12 (2H, s, OCH2Ph), 6.83 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.03 (1H, J1 = 8.0 Hz, J2 = 1.2 Ph), 7.27-7.28 (1H, m, Ph), 7.32-7.35 (3H, m, Ph), 7.73 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.39 (1H, s, NH), 11.80 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.63 (9H, s, 3CH 3 ), 5.12 (2H, s, OCH 2 Ph), 6.83 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.03 (1H, J 1 = 8.0 Hz, J 2 = 1.2 Ph), 7.27-7.28 (1H, m, Ph), 7.32-7.35 (3H, m, Ph ), 7.73 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.39 (1H, s, NH), 11.80 (1H, s, NH)
화합물 211: 1-(3-(3-Compound 211: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-ρ-) Pyridin-2-yl) -3-ρ- 톨릴Tolyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 2.36 (3H, s, CH3), 5.15 (2H, s, OCH2Ph), 6.91 (1H, dd, J1 = 8.0 Hz, J2 = 4.8 Hz, Py), 7.12 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.21 (2H, d, J = 8.4 Hz, Ph), 7.29-7.31 (1H, m, Ph), 7.35-7.38 (3H, m, Ph), 7.54 (2H, d, J = 8.4 Hz, Ph), 7.82 (1H, dd, J1 = 4.8 Hz, J2 = 1.2 Hz, Py), 8.70 (1H, s, NH), 13.45 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.36 (3H, s, CH 3 ), 5.15 (2H, s, OCH 2 Ph), 6.91 (1H, dd, J 1 = 8.0 Hz, J 2 = 4.8 Hz, Py), 7.12 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.21 (2H, d, J = 8.4 Hz, Ph), 7.29-7.31 (1H, m, Ph), 7.35-7.38 (3H, m, Ph), 7.54 (2H, d, J = 8.4 Hz, Ph), 7.82 (1H, dd, J 1 = 4.8 Hz, J 2 = 1.2 Hz, Py), 8.70 (1H, s, NH), 13.45 (1H, s, NH)
화합물 212: 1-(3-(3-Compound 212: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(3-Pyridin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.16 (2H, s, OCH2Ph), 6.94 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.15 (1H, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 7.20-7.23 (1H, m, Ph), 7.30-7.38 (5H, m, Ph), 7.64-7.67 (1H, m, Ph), 7.78 (1H, t, J = 2.0 Hz, Ph), 7.84 (1H, dd, J1 = 5.2 Hz, J2 = 1.2 Hz, Py), 8.72 (1H, s, NH), 13.70 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.16 (2H, s, OCH 2 Ph), 6.94 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.15 (1H, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 7.20-7.23 (1H, m, Ph), 7.30-7.38 (5H, m, Ph), 7.64-7.67 (1H, m, Ph), 7.78 (1H, t, J = 2.0 Hz, Ph), 7.84 (1H, dd, J 1 = 5.2 Hz, J 2 = 1.2 Hz, Py), 8.72 (1H, s, NH), 13.70 (1H, s, NH)
화합물 213: 1-(3-(3-Compound 213: 1- (3- (3- 클로로벤질옥시Chlorobenzyloxy )피리딘-2-일)-3-(나프탈렌-1-일) Pyridin-2-yl) -3- (naphthalen-1-yl) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.19 (2H, s, OCH2Ph), 6.96 (1H, dd, J1 = 8.0 Hz, J2 = 5.2 Hz, Py), 7.18 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, Py), 7.33-7.41 (4H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.57 (1H, d, J = 7.6 Hz, Ph), 7.81-7.85 (2H, m, Ph+Py), 7.89-7.91 (1H, m, Ph), 7.80 (1H, d, J = 7.2 Hz, Ph), 7.07-7.09 (1H, m, Ph), 8.89 (1H, s, NH), 13.76 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.19 (2H, s, OCH 2 Ph), 6.96 (1H, dd, J 1 = 8.0 Hz, J 2 = 5.2 Hz, Py), 7.18 (1H, dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, Py), 7.33-7.41 (4H, m, Ph), 7.50-7.54 (2H, m, Ph), 7.57 (1H, d, J = 7.6 Hz, Ph), 7.81-7.85 (2H, m , Ph + Py), 7.89-7.91 (1H, m, Ph), 7.80 (1H, d, J = 7.2 Hz, Ph), 7.07-7.09 (1H, m, Ph), 8.89 (1H, s, NH) , 13.76 (1H, s, NH)
화합물 214: 1-(3-(3-Compound 214: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-이소프로필 Pyrazin-2-yl) -3-isopropyl 티오유레아Thiourea
1H NMR (300 MHz, CDCl3) δ = 1.35 (6H, d, J = 4.2 Hz, 2CH3), 4.50-4.63 (1H, m, Ph), 5.44 (2H, s, OCH2Ph), 7.01-7.07 (1H, m, Ph), 7.20 (1H, d, J = 7.5 Hz, Ph), 7.32-7.39 (1H, m, Ph), 7.68 (1H, d, J = 3.3 Hz, pyrazine), 7.70 (1H, d, J = 3.3 Hz, pyrazine), 8.39 (1H, s, NH), 11.00 (1H, s, NH)
1 H NMR (300 MHz, CDCl 3 ) δ = 1.35 (6H, d, J = 4.2 Hz, 2CH 3 ), 4.50-4.63 (1H, m, Ph), 5.44 (2H, s, OCH 2 Ph), 7.01 -7.07 (1H, m, Ph), 7.20 (1H, d, J = 7.5 Hz, Ph), 7.32-7.39 (1H, m, Ph), 7.68 (1H, d, J = 3.3 Hz, pyrazine), 7.70 (1H, d, J = 3.3 Hz, pyrazine), 8.39 (1H, s, NH), 11.00 (1H, s, NH)
화합물 215: 1-(3-(3-Compound 215: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-Pyrazin-2-yl) -3- 삼차부틸Tert-butyl 티오유레아Thiourea ;;
1H NMR (300 MHz, CDCl3) δ = 1.61 (9H, s, 3CH3), 5.44 (2H, s, OCH2Ph), 7.01-7.06 (1H, m, Ph), 7.13 (1H, d, J = 9.0 Hz, Ph), 7.19-7.29 (1H, m, Ph), 7.31-7.38 (1H, m, Ph), 7.65 (1H, d, J = 3.0 Hz, pyrazine), 7.67 (1H, d, J = 3.0 Hz, pyrazine), 8.28 (1H, s, NH), 11.27 (1H, s, NH)
1 H NMR (300 MHz, CDCl 3 ) δ = 1.61 (9H, s, 3CH 3 ), 5.44 (2H, s, OCH 2 Ph), 7.01-7.06 (1H, m, Ph), 7.13 (1H, d, J = 9.0 Hz, Ph), 7.19-7.29 (1H, m, Ph), 7.31-7.38 (1H, m, Ph), 7.65 (1H, d, J = 3.0 Hz, pyrazine), 7.67 (1H, d, J = 3.0 Hz, pyrazine), 8.28 (1H, s, NH), 11.27 (1H, s, NH)
화합물 216: 1-(3-(3-Compound 216: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-벤질 Pyrazin-2-yl) -3-benzyl 티오유레아Thiourea
1H NMR (300 MHz, CDCl3) δ = 4.92 (2H, d, J = 5.7 Hz, OCH2Ph), 5.48 (2H, s, OCH2Ph), 7.15-7.20 (1H, m, Ph), 7.24-7.31 (2H, m, Ph), 7.34-7.37 (4H, m, Ph), 7.41-7.49 (2H, m, Ph), 7.82 (1H, d, J = 3.0 Hz, pyrazine), 7.85 (1H, d, J = 3.0 Hz, pyrazine), 8.92 (1H, s, NH), 11.35 (1H, s, NH)
1 H NMR (300 MHz, CDCl 3 ) δ = 4.92 (2H, d, J = 5.7 Hz, OCH 2 Ph), 5.48 (2H, s, OCH 2 Ph), 7.15-7.20 (1H, m, Ph), 7.24-7.31 (2H, m, Ph), 7.34-7.37 (4H, m, Ph), 7.41-7.49 (2H, m, Ph), 7.82 (1H, d, J = 3.0 Hz, pyrazine), 7.85 (1H , d, J = 3.0 Hz, pyrazine), 8.92 (1H, s, NH), 11.35 (1H, s, NH)
화합물 217: 1-(3-(3-Compound 217: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 티오유레아Thiourea
1H NMR (300 MHz, CDCl3) δ = 5.49 (2H, s, OCH2Ph), 7.09-7.20 (1H, m, Ph), 7.26-7.33 (1H, m, Ph), 7.32-7.51 (4H, m, Ph), 7.60 (1H, d, J = 8.4 Hz, Ph), 7.90-7.97 (3H, m, pyrazine+Ph), 9.40 (1H, s, NH), 12.75 (1H, s, NH)
1 H NMR (300 MHz, CDCl 3 ) δ = 5.49 (2H, s, OCH 2 Ph), 7.09-7.20 (1H, m, Ph), 7.26-7.33 (1H, m, Ph), 7.32-7.51 (4H , m, Ph), 7.60 (1H, d, J = 8.4 Hz, Ph), 7.90-7.97 (3H, m, pyrazine + Ph), 9.40 (1H, s, NH), 12.75 (1H, s, NH)
화합물 218: 1-(3-(3-Compound 218: 1- (3- (3- 플루오르벤질옥시Fluorbenzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 티오유레아Thiourea
1H NMR (300 MHz, CDCl3) δ = 1.50 (3H, s, CH3), 5.59 (2H, s, OCH2Ph), 7.27-7.36 (4H, m, Ph), 7.44-7.49 (2H, m, Ph), 7.62 (1H, d, J = 7.5 Hz, Ph), 7.74-7.77 (2H, m, pyrazine+Ph), 7.81 (1H, d, J = 3.0 Hz, pyrazine), 8.63 (1H, s, NH), 13.09 (1H, s, NH)
1 H NMR (300 MHz, CDCl 3 ) δ = 1.50 (3H, s, CH 3 ), 5.59 (2H, s, OCH 2 Ph), 7.27-7.36 (4H, m, Ph), 7.44-7.49 (2H, m, Ph), 7.62 (1H, d, J = 7.5 Hz, Ph), 7.74-7.77 (2H, m, pyrazine + Ph), 7.81 (1H, d, J = 3.0 Hz, pyrazine), 8.63 (1H, s, NH), 13.09 (1H, s, NH)
화합물 219: 1-(3-(2-Compound 219: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-이소프로필 Pyrazin-2-yl) -3-isopropyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH3), 4.55-4.60 (1H, m, Ph), 5.55 (2H, s, OCH2Ph), 7.28-7.32 (2H, m, Ph), 7.42-7.45 (2H, m, Ph), 7.69 (1H, d, J = 3.2 Hz, pyrazine), 7.70 (1H, d, J = 3.2 Hz, pyrazine), 8.40 (1H, s, NH), 11.06 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 1.35 (6H, d, J = 6.8 Hz, 2CH 3 ), 4.55-4.60 (1H, m, Ph), 5.55 (2H, s, OCH 2 Ph), 7.28 -7.32 (2H, m, Ph), 7.42-7.45 (2H, m, Ph), 7.69 (1H, d, J = 3.2 Hz, pyrazine), 7.70 (1H, d, J = 3.2 Hz, pyrazine), 8.40 (1H, s, NH), 11.06 (1H, s, NH)
화합물 220: 1-(3-(2-Compound 220: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-벤질 Pyrazin-2-yl) -3-benzyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 4.99 (2H, d, J = 5.2 Hz, OCH2Ph), 5.56 (2H, s, OCH2Ph), 7.29-7.33 (3H, m, Ph), 7.34-7.41 (4H, m, Ph), 7.43-7.46 (2H, m, Ph), 7.62 (1H, d, J = 3.2 Hz, pyrazine), 7.71 (1H, d, J = 3.2 Hz, pyrazine), 8.56 (1H, s, NH), 11.50 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 4.99 (2H, d, J = 5.2 Hz, OCH 2 Ph), 5.56 (2H, s, OCH 2 Ph), 7.29-7.33 (3H, m, Ph), 7.34-7.41 (4H, m, Ph), 7.43-7.46 (2H, m, Ph), 7.62 (1H, d, J = 3.2 Hz, pyrazine), 7.71 (1H, d, J = 3.2 Hz, pyrazine), 8.56 (1H, s, NH), 11.50 (1H, s, NH)
화합물 221: 1-(3-(2-Compound 221: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-(3-Pyrazin-2-yl) -3- (3- 클로로페닐Chlorophenyl ) ) 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 5.60 (2H, s, OCH2Ph), 7.22-7.25 (1H, m, Ph), 7.31-7.35 (3H, m, Ph), 7.44-7.49 (2H, m, Ph), 7.44-7.49 (2H, m, Ph), 7.62 (1H, d, J = 7.6 Hz, Ph), 7.75-7.76 (2H, m, pyrazine+Ph), 7.81 (1H, d, J = 3.2 Hz, pyrazine), 8.63 (1H, s, NH), 13.09 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 5.60 (2H, s, OCH 2 Ph), 7.22-7.25 (1H, m, Ph), 7.31-7.35 (3H, m, Ph), 7.44-7.49 (2H , m, Ph), 7.44-7.49 (2H, m, Ph), 7.62 (1H, d, J = 7.6 Hz, Ph), 7.75-7.76 (2H, m, pyrazine + Ph), 7.81 (1H, d, J = 3.2 Hz, pyrazine), 8.63 (1H, s, NH), 13.09 (1H, s, NH)
화합물 222: 1-(3-(2-Compound 222: 1- (3- (2- 클로로벤질옥시Chlorobenzyloxy )피라진-2-일)-3-ρ-) Pyrazin-2-yl) -3-ρ- 톨릴Tolyl 티오유레아Thiourea
1H NMR (400 MHz, CDCl3) δ = 2.36 (3H, s, CH3), 5.59 (2H, s, OCH2Ph), 7.21 (2H, d, J = 8.4 Hz, Ph), 7.30-7.34 (2H, m, Ph), 7.43-7.48 (2H, m, Ph), 7.50 (2H, d, J = 8.4 Hz, Ph), 7.74 (1H, d, J = 3.2 Hz, pyrazine), 7.78 (1H, d, J = 3.2 Hz, pyrazine), 8.61 (1H, s, NH), 12.88 (1H, s, NH)
1 H NMR (400 MHz, CDCl 3 ) δ = 2.36 (3H, s, CH 3 ), 5.59 (2H, s, OCH 2 Ph), 7.21 (2H, d, J = 8.4 Hz, Ph), 7.30-7.34 (2H, m, Ph), 7.43-7.48 (2H, m, Ph), 7.50 (2H, d, J = 8.4 Hz, Ph), 7.74 (1H, d, J = 3.2 Hz, pyrazine), 7.78 (1H , d, J = 3.2 Hz, pyrazine), 8.61 (1H, s, NH), 12.88 (1H, s, NH)
제조예Manufacturing example . . 유레아Urea 유도체의 제제화 Formulation of Derivatives
본 발명에 따른 유레아 유도체는 여러 형태로 제제화가 가능하다. 이하, 본 발명의 이해를 돕기 위하여 바람직한 제조예를 들어 본 발명을 더욱 상세하게 설명한다. 그러나 하기의 제조예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 이에 의해 본 발명의 내용이 한정되는 것은 아니다.
Urea derivatives according to the invention can be formulated in many forms. Hereinafter, the present invention will be described in more detail with reference to preferred production examples in order to aid the understanding of the present invention. However, the following preparation examples are merely provided to more easily understand the present invention, thereby not limiting the contents of the present invention.
제조예Manufacturing example 1.1 정제 ( 1.1 tablets ( 직접가압Direct pressure ))
활성성분 5.0 mg을 체로 친 후, 락토스 14.1 mg, 크로스포비돈 USNF 0.8 mg 및 마그네슘 스테아레이트 0.1 mg을 혼합하고 가압하여 정제로 만들었다.
After sifting 5.0 mg of the active ingredient, 14.1 mg of lactose, 0.8 mg of crospovidone USNF and 0.1 mg of magnesium stearate were mixed and pressurized into tablets.
제조예Manufacturing example 1.2. 정제 (습식 조립) 1.2. Tablets (wet assembly)
활성성분 5.0 ㎎을 체로 친 후, 락토스 16.0 ㎎과 녹말 4.0 ㎎을 섞었다. 폴리솔베이트 80 0.3 ㎎을 순수한 물에 녹인 후 이 용액의 적당량을 첨가한 다음, 미립화하였다. 건조 후에 미립을 체질한 후 콜로이달 실리콘 디옥사이드 2.7 ㎎ 및 마그네슘 스테아레이트 2.0 ㎎과 섞었다. 미립을 가압하여 정제로 만들었다.
After 5.0 mg of the active ingredient was sieved, 16.0 mg of lactose and 4.0 mg of starch were mixed. 0.3 mg of Polysorbate 80 was dissolved in pure water, and an appropriate amount of this solution was added, followed by atomization. After drying, the granules were sieved and mixed with 2.7 mg of colloidal silicon dioxide and 2.0 mg of magnesium stearate. The granules were pressurized to make tablets.
제조예Manufacturing example 2. 분말과 2. with powder 캡슐제Capsule
활성성분 5.0 ㎎을 체로 친 후에, 락토스 14.8 ㎎, 폴리비닐 피롤리돈 10.0 ㎎, 마그네슘 스테아레이트 0.2 ㎎와 함께 섞은 후, 단단한 No. 5 젤라틴 캡슐에 채웠다.
After sifting 5.0 mg of the active ingredient, the mixture was mixed with 14.8 mg of lactose, 10.0 mg of polyvinyl pyrrolidone, and 0.2 mg of magnesium stearate, followed by solid No. 5 gelatin capsules.
제조예Manufacturing example 3. 주사제 3. Injection
활성성분으로 100 mg을 함유시키고, 그 외에 만니톨 180 mg, Na2HPO412H2O 26 mg 및 증류수 2974 mg를 함유시켜 주사제를 제조하였다.
Injectables were prepared by containing 100 mg of the active ingredient, followed by the addition of 180 mg of mannitol, 26 mg of Na 2 HPO 4 12H 2 O and 2974 mg of distilled water.
실험예Experimental Example
본 발명에 따라 제조된 유레아 유도체에 대하여 베타 아밀로이드에 의해 손상된 미토콘드리아의 기능회복 정도 측정을 수행하였으며, 이를 백분율로 표시하였다. 베타 아밀로이드에서 손상된 정도를 100% 로 두고 베타 아밀로이드가 없는 정상상태를 0% 로 표시하였다.
The urea derivative prepared according to the present invention was measured for the degree of functional recovery of mitochondria damaged by beta amyloid, which is expressed as a percentage. The degree of damage in beta amyloid was set at 100% and the normal state without beta amyloid was expressed as 0%.
실험예Experimental Example 1. 베타 아밀로이드에 의한 미토콘드리아 손상 ( 1. Mitochondrial damage caused by beta amyloid ( JCJC -1 -One mitochondrialmitochondrial membrane membrane potentialpotential assayassay ))
실험에 쓰인 세포주는 HT-22 (mouse hippocampal cell line)으로서 10%(v/v)의 FBS와 항생제를 포함하는 Dulbecco’s Modified Eagle’s Medium (DMEM, GIBCO)을 사용하여 37 ℃, 5% CO2 하에서 배양하였다. The cell line used in this experiment was HT-22 (mouse hippocampal cell line) at 37 ° C and 5% CO 2 using Dulbecco's Modified Eagle's Medium (DMEM, GIBCO) containing 10% (v / v) FBS and antibiotics. Incubated under
투명한 96 well plate 에 HT-22 세포를 각 well 당 30,000개씩 하루 전에 seeding하여 준비하고, JC-1 dye (Stratagen, USA)를 Phenol Red를 포함하지 않는 Opti-MEM에 희석하여 7.5 μM 농도로 1시간 15분간 37 ℃, 5% CO2 하에서 배양하였다. 염색된 세포를 Phosphate buffered saline (PBS) 로 두 번 세척한 후에 각 화합물을 well 당 최종농도가 5μM이 되도록 처리하고 10분간 37℃에서 incubation 하였다. 여기에 10 mM의 베타 아밀로이드 용액 (American peptide, 1-42)를 추가로 첨가한 후 매 한 시간마다 plate reader를 이용하여 530/580(ex/em) nm와 485/530(ex/em) nm에서의 형광신호를 측정한다. 580 nm (red) 와 530 nm (green)에서 측정되는 형광신호의 비율을 측정하여 각 화합물을 사용했을 때의 green to red ratio가 화합물을 사용하지 않았을 때의 변화량과 비교하여 얼마나 달라졌는지를 퍼센트로 표시하였으며, 하기 표 1에 나타내었다.
Seed 30,000 HT-22 cells per day in a clear 96 well plate, and prepare JC-1 dye (Stratagen, USA) in Opti-MEM without Phenol Red for 1 hour at 7.5 μM concentration. 15 minutes at 37 ° C., 5% CO 2 Incubated under After staining the stained cells twice with Phosphate buffered saline (PBS), each compound was treated to a final concentration of 5μM per well and incubated at 37 ℃ for 10 minutes. An additional 10 mM beta amyloid solution (American peptide, 1-42) was added to the plate reader every hour for 530/580 (ex / em) nm and 485/530 (ex / em) nm. Measure the fluorescence signal at. Measure the ratio of the fluorescence signal measured at 580 nm (red) and 530 nm (green) to determine how much the green to red ratio with each compound is compared to the amount of change without the compound. It is shown in Table 1 below.
실험예Experimental Example 2. 베타 아밀로이드에 의해 2. by beta amyloid 감소된Reduced ATPATP 생산 능력의 회복력 % (cellular % Resilience of production capacity ATPATP levellevel assayassay ))
투명한 96 well plate 에 HT-22 세포를 각 well 당 30,000개씩 하루 전에 seeding하여 준비한 후, 각 화합물 (10 mM)을 함유한 25 mL 용액을 각 well 에 첨가하여 10분간 배양한 후에 10 mM의 베타 아밀로이드 용액 (American peptide, 1-42)를 추가로 첨가하고 37 ℃, 5% CO2 하에서 6시간 동안 배양하였다. 1% Triton-X 100 in TBST 버퍼를 이용하여 세포를 lysis 한 후에 BCA 단백질 정량 킷 (Thermo Scientific) 을 이용하여 각 well당 lysates 의 단백질 량을 측정하였다. 각 well 에서 동일한 양의 cell lysates 를 취하여 96 well plate 에 옮긴 후에 각 well 당 생성되는 ATP의 양을 ATP determination kit (Invitrogen)을 이용하여 측정하였다. 약물처리하지 않은 콘트롤 군의 ATP 생성량과 베타 아밀로이드로 세포독성을 유발한 군의 ATP 생성량간의 차이를 계산한 후 이 값에 비해 약물 처리했을 때 ATP 생성량이 얼마나 변화했는지를 퍼센트로 표시하였으며, 이를 하기 표 1에 나타내었다. After seeding 30,000 HT-22 cells in each well on a clear 96 well plate one day ago, a 25 mL solution containing each compound (10 mM) was added to each well and incubated for 10 minutes, followed by 10 mM beta amyloid. Additional solution (American peptide, 1-42) was added and 37 ° C., 5% CO 2 Incubated for 6 hours. After lysis of cells using 1% Triton-X 100 in TBST buffer, the protein content of lysates per well was measured using a BCA protein quantitative kit (Thermo Scientific). The same amount of cell lysates was taken from each well and transferred to a 96 well plate, and the amount of ATP generated per well was measured using an ATP determination kit (Invitrogen). The difference between ATP production in the control group and the drug-induced beta amyloid-induced ATP production was calculated and expressed as a percentage of the change in ATP production compared to this value. Table 1 shows.
Claims (19)
<화학식 1>
상기 화학식 1에서,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,
X는 탄소 또는 질소이며,
Y는 산소 또는 황이며,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.Urea derivatives represented by the following general formula (1):
≪ Formula 1 >
In Chemical Formula 1,
R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X is carbon or nitrogen,
Y is oxygen or sulfur,
R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
1-(3-(벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-벤질 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-페닐 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-벤질 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-페닐 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-벤질 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-페닐 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-벤질 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-페닐 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-에틸 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-에틸 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-에틸 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-에틸 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-에틸 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-싸이클로헵틸 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-에틸 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;
1-(3-(4-플루오르벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(2-(피페라진-1일)에틸) 유레아;
1-(3-(4-클로로벤질옥시)피리딘-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-벤질 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-페닐 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-벤질 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-페닐 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-벤질 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-페닐 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(3,4-다이틀로로페닐) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-벤질 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-페닐 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(2-플루오르페닐) 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(3-플루오르페닐) 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(3,4-다이클로로페닐) 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(나프탈렌-1-일) 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(4-(트리플루오르메틸)페닐) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-에틸 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-삼차부틸 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-에틸 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-삼차부틸 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-에틸 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-삼차부틸 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-에틸 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-삼차부틸 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(아다만탄-1-일) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-에틸 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-삼차부틸 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-싸이클로헵틸 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(2,4,4-트리메틸펜탄-2-일) 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-에틸 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-삼차부틸 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(4-플루오르벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-(피페라진-1-일)에틸) 유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-(피페라진-1-일)에틸) 유레아;
1-(3-(3-클로로벤질옥시)피라진-2-일)-3-(2-(4-메틸피페라진-1-일)에틸) 유레아;
1-(3-(4-클로로벤질옥시)피라진-2-일)-3-(2-클로로에틸) 유레아;
1-(3-(2-니트로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3-니트로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(4-니트로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(2-메틸벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3-메틸벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3-메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(2-플루오로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3-플루오로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(4-플루오로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(4-메틸벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(4-메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(2-메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(2,4-다이메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(3,4-다이메톡시벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-에틸 티오유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-벤질 티오유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;
1-(3-(벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-에틸 티오유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-벤질 티오유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;
1-(3-(3-플루오르벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-에틸 티오유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;
1-(3-(2-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-에틸 티오유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-이소프로필 티오유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-삼차부틸 티오유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-ρ-톨릴 티오유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(3-클로로페닐) 티오유레아;
1-(3-(3-클로로벤질옥시)피리딘-2-일)-3-(나프탈렌-1-일) 티오유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-이소프로필 티오유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-삼차부틸 티오유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-벤질 티오유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-(3-클로로페닐) 티오유레아;
1-(3-(3-플루오르벤질옥시)피라진-2-일)-3-ρ-톨릴 티오유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-이소프로필 티오유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-벤질 티오유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-(3-클로로페닐) 티오유레아;
1-(3-(2-클로로벤질옥시)피라진-2-일)-3-ρ-톨릴 티오유레아; 인 것을 특징으로 하는 유레아 유도체.The method of claim 1, wherein the urea derivative is
1- (3- (benzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3-benzyl urea;
1- (3- (benzyloxy) pyridin-2-yl) -3-phenyl urea;
1- (3- (benzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (3-Fluorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-benzyl urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-phenyl urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-benzyl urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-phenyl urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-benzyl urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-phenyl urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3-ethyl urea;
1- (3- (benzyloxy) pyridin-2-yl) -3-tert-butyl urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ethylurea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-cycloheptyl urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-ethyl urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (2- (piperazin-1yl) ethyl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (2- (piperazin-1 yl) ethyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (2- (piperazin-1yl) ethyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (2- (piperazin-1yl) ethyl) urea;
1- (3- (4-chlorobenzyloxy) pyridin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (3,4-ditrolophenyl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3-benzyl urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3-phenyl urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3,4-difluorophenyl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-benzyl urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-phenyl urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3,4-difluorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-benzyl urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-phenyl urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (3,4-difluorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-benzyl urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-phenyl urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (2-fluorophenyl) urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (3-fluorophenyl) urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (3,4-dichlorophenyl) urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (naphthalen-1-yl) urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (4- (trifluoromethyl) phenyl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3-ethyl urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (adamantan-1-yl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-cycloheptyl urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (2,4,4-trimethylpentan-2-yl) urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-ethyl urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3-tert-butyl urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (benzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (4-fluorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (piperazin-1-yl) ethyl) urea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (piperazin-1-yl) ethyl) urea;
1- (3- (3-chlorobenzyloxy) pyrazin-2-yl) -3- (2- (4-methylpiperazin-1-yl) ethyl) urea;
1- (3- (4-chlorobenzyloxy) pyrazin-2-yl) -3- (2-chloroethyl) urea;
1- (3- (2-nitrobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3-nitrobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (4-nitrobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (2-methylbenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3-methylbenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3-methoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (2-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (4-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (4-methylbenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (4-methoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (2-methoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (2,4-dimethoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (3,4-dimethoxybenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) urea;
1- (3- (benzyloxy) pyridin-2-yl) -3-ethyl thiourea;
1- (3- (benzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
1- (3- (benzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
1- (3- (benzyloxy) pyridin-2-yl) -3-benzyl thiourea;
1- (3- (benzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
1- (3- (benzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ethyl thiourea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-benzyl thiourea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
1- (3- (3-fluorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ethyl thiourea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
1- (3- (2-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ethyl thiourea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-isopropyl thiourea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-tert-butyl thiourea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3-ρ-tolyl thiourea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (3-chlorophenyl) thiourea;
1- (3- (3-chlorobenzyloxy) pyridin-2-yl) -3- (naphthalen-1-yl) thiourea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-isopropyl thiourea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-tert-butyl thiourea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-benzyl thiourea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) thiourea;
1- (3- (3-fluorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl thiourea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-isopropyl thiourea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-benzyl thiourea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3- (3-chlorophenyl) thiourea;
1- (3- (2-chlorobenzyloxy) pyrazin-2-yl) -3-ρ-tolyl thiourea; Urea derivatives, characterized in that.
<화학식 2>
<화학식 1>
상기 화학식 1 또는 2에서,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,
X는 탄소 또는 질소이며,
Y는 산소 또는 황이며,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.A method for preparing a urea derivative comprising the step of preparing a compound of formula 1 by reacting a compound of formula 2 with an isocyanate compound or isothiocyanate compound:
(2)
≪ Formula 1 >
In the above formula (1) or (2)
R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X is carbon or nitrogen,
Y is oxygen or sulfur,
R 6 is a second alkyl, pephenyl, benzyl, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group containing a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group It may be a third alkyl group substituted with halogen.
<화학식 3>
상기 화학식 3에서,
X는 탄소 또는 질소이다.The method of claim 6, wherein the compound of Formula 2 is prepared by reacting a compound of Formula 3 with a benzyl halide compound.
(3)
In Formula 3,
X is carbon or nitrogen.
<화학식 4>
상기 화학식 4에서,
X는 탄소 또는 질소이다.The method of claim 6, wherein the compound of Formula 2 is prepared by reacting a compound of Formula 4 with a benzyl alcohol compound:
≪ Formula 4 >
In Formula 4,
X is carbon or nitrogen.
<화학식 5>
<화학식 1>
상기 화학식 1 또는 5에서,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,
X는 탄소 또는 질소이며,
Y는 산소 또는 황이며,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.A method for preparing a urea derivative comprising reacting a compound of Formula 5 with a benzyl halide compound or a benzyl alcohol compound to produce a compound of Formula 1:
≪ Formula 5 >
≪ Formula 1 >
In Chemical Formula 1 or 5,
R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X is carbon or nitrogen,
Y is oxygen or sulfur,
R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
<화학식 3>
상기 화학식 3에서,
X는 탄소 또는 질소이다.The method of claim 11, wherein the compound of Formula 5 is prepared by reacting a compound of Formula 3 with an isocyanate compound or an isothiocyanate compound:
(3)
In Formula 3,
X is carbon or nitrogen.
<화학식 6>
상기 화학식 6에서,
X는 탄소 또는 질소이며,
Y는 산소 또는 황이며,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.The method of claim 11, wherein the compound of Chemical Formula 5 is prepared by debenzylating a compound of Chemical Formula 6.
(6)
In Formula 6,
X is carbon or nitrogen,
Y is oxygen or sulfur,
R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
<화학식 7>
상기 화학식 7에서,
X는 탄소 또는 질소이다.The method of claim 15, wherein the compound of Chemical Formula 6 is prepared by reacting a compound of Chemical Formula 7 with an isocyanate compound or an isothiocyanate compound.
≪ Formula 7 >
In Formula 7,
X is carbon or nitrogen.
<화학식 1>
상기 화학식 1에서,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,
X는 탄소 또는 질소이며,
Y는 산소 또는 황이며,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.A pharmaceutical composition for inhibiting the action of mPTP, comprising the urea derivative represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:
≪ Formula 1 >
In Chemical Formula 1,
R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X is carbon or nitrogen,
Y is oxygen or sulfur,
R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
<화학식 1>
상기 화학식 1에서,
R1, R2, R3, R4, R5는 서로 동일하거나 상이할 수 있고, 각각 독립적으로 수소, 할로겐, 니트로, 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 제 1 알킬기 또는 탄소 수 1 내지 6 개의 직쇄상, 분쇄상 또는 고리상 탄소사슬을 포함하는 알콕시기일 수 있으며,
X는 탄소 또는 질소이며,
Y는 산소 또는 황이며,
R6는 탄소 수 1 내지 8개의 직쇄상, 분쇄상 또는 고리상의 탄소사슬을 포함하는 제 2 알킬기, 페닐기, 벤질기, 토릴기, 나프틸기, 아다만틸기, 피페라질기, 메틸피페라질기, 에틸피페라질기, 에틸메틸피페라질기, 피롤리딜기, 피페리딜기, 할로페닐기, 디할로페닐기, 할로벤질기, 디할로벤질기, 트리할로메틸페닐기 또는 상기 제 2 알킬기의 하나 이상의 수소가 할로겐으로 치환된 제 3 알킬기일 수 있다.A pharmaceutical composition for treating cranial nerve disease, comprising the urea derivative represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:
≪ Formula 1 >
In Chemical Formula 1,
R 1 , R 2 , R 3 , R 4 , R 5 may be the same or different from each other, and each independently include hydrogen, halogen, nitro, straight, crushed or cyclic carbon chain having 1 to 6 carbon atoms. It may be a first alkyl group or an alkoxy group containing a linear, pulverized or cyclic carbon chain having 1 to 6 carbon atoms,
X is carbon or nitrogen,
Y is oxygen or sulfur,
R 6 is a second alkyl group, phenyl group, benzyl group, toryl group, naphthyl group, adamantyl group, piperazil group, methylpiperazyl group, including a linear, pulverized or cyclic carbon chain having 1 to 8 carbon atoms, At least one hydrogen of the ethyl piperazyl group, ethyl methyl piperazil group, pyrrolidyl group, piperidyl group, halophenyl group, dihalophenyl group, halobenzyl group, dihalbenzyl group, trihalomethylphenyl group or the second alkyl group is halogen It may be a third alkyl group substituted with.
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