KR102131022B1 - Pyrimininone derivative compounds and use thereof - Google Patents

Pyrimininone derivative compounds and use thereof Download PDF

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KR102131022B1
KR102131022B1 KR1020180081325A KR20180081325A KR102131022B1 KR 102131022 B1 KR102131022 B1 KR 102131022B1 KR 1020180081325 A KR1020180081325 A KR 1020180081325A KR 20180081325 A KR20180081325 A KR 20180081325A KR 102131022 B1 KR102131022 B1 KR 102131022B1
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methyl
biphenyl
oxadiazole
oxadiazol
butyl
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김성헌
정원근
유병욱
김학도
양덕모
이성국
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보령제약 주식회사
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Abstract

본 발명은 피리미디논 유도체, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염을 제공한다. 본 발명의 화합물은 고혈압 및/또는 당뇨병의 치료, 예방 또는 개선 활성을 나타낸다.The present invention provides pyrimidinone derivatives, optical isomers thereof, or pharmaceutically acceptable salts thereof. The compounds of the present invention exhibit the treatment, prevention or improvement activity of hypertension and/or diabetes.

Description

피리미디논 유도체 화합물 및 이의 용도 {Pyrimininone derivative compounds and use thereof}Pyrimininone derivative compounds and use thereof

본 발명은 피리미디논 유도체 화합물 및 이의 용도에 관한 것이다.The present invention relates to pyrimidinone derivative compounds and uses thereof.

고혈압은 만성 질환으로 아직까지 원인이 밝혀지지 않은 본태성 고혈압(1차성 고혈압)이 전체 환자의 90 %를 차지하며, 고혈압 상태가 지속될 경우 심장마비, 뇌졸중 등의 치명적인 질환이 발생할 가능성이 증가한다. 특히, 대사성 질환의 하나인 당뇨가 동반되는 경우 그 치명성은 수배가 증가하게 된다. Hypertension is a chronic disease. Essential hypertension (primary hypertension), which has not yet been identified, accounts for 90% of all patients, and if hypertension persists, the likelihood of fatal diseases such as heart attack and stroke increases. Particularly, when diabetes, which is one of metabolic diseases, is accompanied, the fatality increases several times.

안지오텐신 I으로부터 안지오텐신 전환 효소에 의해 생성되는 안지오텐신 II는 세포막 단백질로서 혈관 세포벽에 존재하는 안지오텐신 II 수용체를 통해 혈압을 증가시킨다는 사실이 알려져 있다. 따라서, 안지오텐신 II 길항제는 안지오텐신에 의해 발생되는 고혈압을 치료하는데 사용되었다. 지금까지, 경구 투여 안지오텐신 II 길항제로서 개발된 약물로, 로사르탄(losartan), 칸데사르탄 실레세틸(candesartan cilexetil), 올메사르탄 메독소밀(olmesartan medoxomil), 텔미사르탄(telmisartan), 피마사르탄(fimasartan) 등이 알려져 있다.It is known that angiotensin II, produced by angiotensin converting enzyme from angiotensin I, is a cell membrane protein that increases blood pressure through the angiotensin II receptor present on the vascular cell wall. Thus, angiotensin II antagonists have been used to treat hypertension caused by angiotensin. So far, drugs developed as orally administered angiotensin II antagonists, losartan, candesartan cilexetil, olmesartan medoxomil, telmisartan, pimasartan (fimasartan) and the like are known.

한편, 당뇨병은 혈중 혈당 조절에 문제가 발생하며, 이로 인해 신장 질환, 혈관 질환 등이 발생하고 욕창, 실명, 신부전 등으로 진행하여 심한 경우 생명을 위협하는 질환이다.On the other hand, diabetes has a problem in regulating blood sugar in the blood, which causes kidney disease, vascular disease, etc., and progresses to bedsores, blindness, kidney failure, etc., which is a life-threatening disease.

TZD(티아졸리딘디온)로 알려진 약물군은 PPARγ를 타겟으로 하며, 혈당 조절 이상 환자에 대해 인슐린에 대한 저항성을 완화시킴으로서 혈당 조절 능력을 회복시켜 주는 약물이다. 이러한 TZD 계열의 약물은 핵 수용체인 PPARγ를 활성화시키는데, 이로 인해 지방대사, 당대사 등 다양한 유전자의 발현이 증가하게 된다고 알려져 있다. 이로 인해 의도하지 않게 부종이나 비만 등이 부작용으로 나타나며, 이러한 부작용을 줄이고 인슐린 내성 극복이라는 약리 효과만을 얻기 위해 부분 활성화제, 선택적 조절제 등의 개발이 시도되어 왔다. The drug group known as TZD (thiazolidinedione) targets PPARγ and is a drug that restores blood sugar control ability by alleviating insulin resistance in patients with abnormal blood sugar control. It is known that the drugs of the TZD family activate the nuclear receptor PPARγ, which increases the expression of various genes such as fat metabolism and glycolysis. Due to this, edema or obesity, etc. appear as unintended side effects, and development of partial activators, selective modulators, etc. has been attempted to reduce these side effects and obtain only the pharmacological effect of overcoming insulin resistance.

고혈압과 당뇨가 동반되는 환자군을 치료하기 위하여, 고혈압과 당뇨를 동시에 치료할 수 있는 치료제의 개발이 진행된 적이 있으나, 실제 약물 개발까지 이루어지지는 못하였다. 이에 본 발명자들은 고혈압 치료와 함께 인슐린 저항성을 조절하는 약물을 개발하고자 하였다.In order to treat a group of patients with hypertension and diabetes, development of a therapeutic agent capable of simultaneously treating hypertension and diabetes has been developed, but actual drug development has not been achieved. Accordingly, the present inventors tried to develop a drug that modulates insulin resistance along with the treatment of hypertension.

본 발명은 고혈압 및/또는 당뇨병의 치료 활성을 나타내는 피리미디논 유도체 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염을 제공하고자 한다. The present invention is to provide a pyrimidinone derivative compound, an optical isomer thereof, or a pharmaceutically acceptable salt thereof that exhibits therapeutic activity for hypertension and/or diabetes.

또한, 본 발명은 본 발명의 피리미디논 유도체 화합물의 제조방법을 제공하고자 한다. In addition, the present invention is to provide a method for producing a pyrimidinone derivative compound of the present invention.

또한, 본 발명은 본 발명의 피리미디논 유도체 화합물의 용도를 제공하고자 한다.In addition, the present invention is to provide a use of the pyrimidinone derivative compound of the present invention.

본 발명자들은 고혈압 및/또는 당뇨병의 치료 활성을 나타내는 피리미디논 유도체 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염을 발견하고 본 발명을 완성하였다.The present inventors have discovered the pyrimidinone derivative compound exhibiting therapeutic activity in hypertension and/or diabetes, an optical isomer thereof, or a pharmaceutically acceptable salt thereof and completed the present invention.

화학식 I의 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염A compound of formula (I), optical isomer thereof, or pharmaceutically acceptable salt thereof

상기 목적에 따라 본 발명에서는, 하기 화학식 I 로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염을 제공한다:According to the above object, the present invention provides a compound represented by the following formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof:

[화학식 I][Formula I]

Figure 112018068967010-pat00001
Figure 112018068967010-pat00001

상기 화학식 I 에서, In the above formula I,

X 는

Figure 112018068967010-pat00002
또는
Figure 112018068967010-pat00003
이고 {여기서, X 가
Figure 112018068967010-pat00004
이면 L2 및 Y 는 아무 것도 아님 (null)},X is
Figure 112018068967010-pat00002
or
Figure 112018068967010-pat00003
And {where X is
Figure 112018068967010-pat00004
L 2 and Y are nothing (null)},

X1 은 N, O, S, CR3 또는 NR4 이고, X 1 is N, O, S, CR 3 or NR 4 ,

X2 는 N, O, S 또는 NR4 이고, X 2 is N, O, S or NR 4 ,

X3 는 N, O, S 또는 CR3 이고, X 3 is N, O, S or CR 3 ,

X4 는 C 또는 N 이고, X 4 is C or N,

X5 는 O 또는 S 이고, X 5 is O or S,

X6 는 N 이고, X 6 is N,

Y 는 H, C1-C6 알킬, NR5R6, OR7, C3-C7 시클로알킬, C5-C10 스파이로 고리, C5-C10 바이사이클릭 고리, 4-7원 헤테로시클로알킬, 아릴 또는 헤테로아릴이고 {여기서, 상기 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6 알킬, NR5R6, OR7, 할로 또는 C1-C6 할로알킬로 치환될 수 있음}, Y is H, C 1 -C 6 alkyl, NR 5 R 6 , OR 7 , C 3 -C 7 cycloalkyl, C 5 -C 10 spiro ring, C 5 -C 10 bicyclic ring, 4-7 membered Heterocycloalkyl, aryl or heteroaryl, wherein at least one H of the aryl or heteroaryl is C 1 -C 6 alkyl, NR 5 R 6 , OR 7 , Can be substituted with halo or C 1 -C 6 haloalkyl},

Z 는

Figure 112018068967010-pat00005
,
Figure 112018068967010-pat00006
또는 -(C=O)O-R8 이고,Z is
Figure 112018068967010-pat00005
,
Figure 112018068967010-pat00006
Or -(C=O)OR 8 ,

Ra1, Ra2, Rb1 및 Rb2 는 각각 독립적으로 H, 할로, C1-C6 알킬 또는 C1-C6 할로알킬이고,R a1 , R a2 , R b1 and R b2 are each independently H, halo, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl,

R1 및 R2 는 각각 독립적으로 H, C1-C6 알킬, C2-C6 알케닐, C2-C6 알키닐 또는 C3-C7 시클로알킬이고,R 1 and R 2 Is each independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 7 cycloalkyl,

R3 및 R4 는 각각 독립적으로 H, C1-C6 알킬 또는 아릴이고,R 3 and R 4 are each independently H, C 1 -C 6 alkyl or aryl,

R5 내지 R8 은 각각 독립적으로 H 또는 C1-C6 알킬이고,R 5 to R 8 are each independently H or C 1 -C 6 alkyl,

L1 은 -(CH2)m- 이고 {여기서, 상기 -(CH2)m- 의 하나 이상의 H 는 중수소로 치환될 수 있음},L 1 is -(CH 2 ) m- (wherein at least one H of -(CH 2 ) m -can be substituted with deuterium),

L2 는 -(CH2)n- 또는

Figure 112018068967010-pat00007
이고 {여기서, 상기 -(CH2)n- 및
Figure 112018068967010-pat00008
의 하나 이상의 H 는 C1-C6 알킬로 치환될 수 있음}, L 2 is -(CH 2 ) n -or
Figure 112018068967010-pat00007
And {where, -(CH 2 ) n -and
Figure 112018068967010-pat00008
At least one H of may be substituted with C 1 -C 6 alkyl},

m 및 n 은 각각 독립적으로 0, 1, 2 또는 3 이고, m and n are each independently 0, 1, 2 or 3,

p 는 1, 2, 3 또는 4 이다.p is 1, 2, 3 or 4.

또한, 본 발명의 일 구체예에 따르면, 상기 화학식 I 로 표시되는 화합물은, In addition, according to an embodiment of the present invention, the compound represented by the formula (I),

X 는

Figure 112018068967010-pat00009
또는
Figure 112018068967010-pat00010
이고 {여기서, X 가
Figure 112018068967010-pat00011
이면 L2 및 Y 는 아무 것도 아님 (null)},X is
Figure 112018068967010-pat00009
or
Figure 112018068967010-pat00010
And {where X is
Figure 112018068967010-pat00011
L 2 and Y are nothing (null)},

X1 은 N, O, S, CR3 또는 NR4 이고, X 1 is N, O, S, CR 3 or NR 4 ,

X2 는 N, O 또는 NR4 이고, X 2 is N, O or NR 4 ,

X3 는 N, O 또는 CR3 이고, X 3 is N, O or CR 3 ,

X4 는 C 또는 N 이고, X 4 is C or N,

X5 는 O 이고, X 5 is O,

X6 는 N 이고, X 6 is N,

Y 는 C1-C4 알킬, NR5R6, OR7, C3-C6 시클로알킬, C5-C10 스파이로 고리, C5-C10 바이사이클릭 고리, 4-6원 헤테로시클로알킬, 아릴 또는 헤테로아릴이고 {여기서, 상기 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C4 알킬, OR7, 할로 또는 C1-C4 할로알킬로 치환될 수 있음}, Y is C 1 -C 4 alkyl, NR 5 R 6 , OR 7 , C 3 -C 6 cycloalkyl, C 5 -C 10 spiro ring, C 5 -C 10 bicyclic ring, 4-6 membered heterocyclo Alkyl, aryl or heteroaryl, wherein at least one H of the aryl or heteroaryl is C 1 -C 4 alkyl, OR 7 , Can be substituted with halo or C 1 -C 4 haloalkyl},

Z 는

Figure 112018068967010-pat00012
,
Figure 112018068967010-pat00013
또는 -(C=O)O-R8 이고,Z is
Figure 112018068967010-pat00012
,
Figure 112018068967010-pat00013
Or -(C=O)OR 8 ,

Ra1, Ra2, Rb1 및 Rb2 는 각각 독립적으로 H 또는 C1-C4 알킬이고,R a1 , R a2 , R b1 and R b2 are each independently H or C 1 -C 4 alkyl,

R1 및 R2 는 각각 독립적으로 C1-C4 알킬이고,R 1 and R 2 Are each independently C 1 -C 4 alkyl,

R3 및 R4 는 각각 독립적으로 H, C1- C4 알킬 또는 아릴이고,R 3 and R 4 are each independently H, C 1 -C 4 alkyl or aryl,

R5 내지 R8 은 각각 독립적으로 H 또는 C1- C4 알킬이고,R 5 to R 8 are each independently H or C 1 -C 4 alkyl,

L1 은 -(CH2)m- 이고 {여기서, 상기 -(CH2)m- 의 하나 이상의 H 는 중수소로 치환될 수 있음},L 1 is -(CH 2 ) m- (wherein at least one H of -(CH 2 ) m -can be substituted with deuterium),

L2 는 -(CH2)n- 또는

Figure 112018068967010-pat00014
이고 {여기서, 상기 -(CH2)n- 및
Figure 112018068967010-pat00015
의 하나 이상의 H 는 C1- C4 알킬로 치환될 수 있음}, L 2 is -(CH 2 ) n -or
Figure 112018068967010-pat00014
And {where, -(CH 2 ) n -and
Figure 112018068967010-pat00015
At least one H of may be substituted with C 1 -C 4 alkyl},

m 및 n 은 각각 독립적으로 0, 1 또는 2 이고, m and n are each independently 0, 1 or 2,

p 는 1 또는 2 이다.p is 1 or 2.

또한, 본 발명의 일 구체예에 따르면, 상기 화학식 I 로 표시되는 화합물은, In addition, according to an embodiment of the present invention, the compound represented by the formula (I),

X 는

Figure 112018068967010-pat00016
,
Figure 112018068967010-pat00017
,
Figure 112018068967010-pat00018
,
Figure 112018068967010-pat00019
,
Figure 112018068967010-pat00020
,
Figure 112018068967010-pat00021
,
Figure 112018068967010-pat00022
,
Figure 112018068967010-pat00023
,
Figure 112018068967010-pat00024
또는
Figure 112018068967010-pat00025
이고 {여기서, X 가
Figure 112018068967010-pat00026
이면 L2 및 Y 는 아무 것도 아님 (null)},X is
Figure 112018068967010-pat00016
,
Figure 112018068967010-pat00017
,
Figure 112018068967010-pat00018
,
Figure 112018068967010-pat00019
,
Figure 112018068967010-pat00020
,
Figure 112018068967010-pat00021
,
Figure 112018068967010-pat00022
,
Figure 112018068967010-pat00023
,
Figure 112018068967010-pat00024
or
Figure 112018068967010-pat00025
And {where X is
Figure 112018068967010-pat00026
L 2 and Y are nothing (null)},

Y 는 C1-C4 알킬, NR5R6, OR7, C3-C6 시클로알킬, C5-C10 스파이로 고리, C5-C10 바이사이클릭 고리, 피페리디닐, 몰폴리닐, 테트라하이드로피라닐, 페닐, 나프탈레닐, 피리디닐 또는 퀴놀리닐이고 {여기서, 상기 페닐, 나프탈레닐, 피리디닐 또는 퀴놀리닐의 하나 이상의 H는 C1-C4 알킬, OR7, F, Cl, Br 또는 CF3로 치환될 수 있음}, Y is C 1 -C 4 alkyl, NR 5 R 6 , OR 7 , C 3 -C 6 cycloalkyl, C 5 -C 10 spiro ring, C 5 -C 10 bicyclic ring, piperidinyl, morphpoly Nil, tetrahydropyranyl, phenyl, naphthalenyl, pyridinyl or quinolinyl, wherein at least one H of the phenyl, naphthalenyl, pyridinyl or quinolinyl is C 1 -C 4 alkyl, OR 7 , Can be substituted with F, Cl, Br or CF 3 },

Z 는

Figure 112018068967010-pat00027
,
Figure 112018068967010-pat00028
또는 -(C=O)O-R8 이고,Z is
Figure 112018068967010-pat00027
,
Figure 112018068967010-pat00028
Or -(C=O)OR 8 ,

R1 및 R2 는 각각 독립적으로 C1-C4 알킬이고,R 1 and R 2 Are each independently C 1 -C 4 alkyl,

R3 및 R4 는 각각 독립적으로 H, C1-C4 알킬 또는 아릴이고,R 3 and R 4 are each independently H, C 1 -C 4 alkyl or aryl,

R5 내지 R8 은 각각 독립적으로 H 또는 C1-C4 알킬이고,R 5 to R 8 are each independently H or C 1 -C 4 alkyl,

L1 은 -(CH2)m- 이고 {여기서, 상기 -(CH2)m- 의 하나 이상의 H 는 중수소로 치환될 수 있음},L 1 is -(CH 2 ) m- (wherein at least one H of -(CH 2 ) m -can be substituted with deuterium),

L2 는 -(CH2)n- 또는

Figure 112018068967010-pat00029
이고 {여기서, 상기 -(CH2)n- 및
Figure 112018068967010-pat00030
의 하나 이상의 H 는 C1-C4 알킬로 치환될 수 있음}, L 2 is -(CH 2 ) n -or
Figure 112018068967010-pat00029
And {where, -(CH 2 ) n -and
Figure 112018068967010-pat00030
At least one H of may be substituted with C 1 -C 4 alkyl},

m 및 n 은 각각 독립적으로 0, 1 또는 2 이고, m and n are each independently 0, 1 or 2,

p 는 1 또는 2 이다.p is 1 or 2.

또한, 본 발명의 구체예에 따르면, 상기 화학식 I 로 표시되는 화합물은, 하기 화합물들로 이루어진 군으로부터 선택된 어느 하나인 화학식 I 로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염일 수 있다:Further, according to an embodiment of the present invention, the compound represented by Formula I may be a compound represented by Formula I, any one selected from the group consisting of the following compounds, an optical isomer thereof, or a pharmaceutically acceptable salt thereof. have:

1) 3-(4'-((2-부틸-5-((3-(2-플루오로페닐)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 1) 3-(4'-((2-butyl-5-((3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

2) 3-(4'-((2-부틸-5-((3-사이클로프로필-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 2) 3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

3) 3-(4'-((2-부틸-5-((3-사이클로프로필-1,2,4-옥소다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 3) 3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxodiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

4) 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 4) 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyriimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

5) 3-(4'-((2-부틸-5-((3-(메톡시메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 5) 3-(4'-((2-butyl-5-((3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

6) 3-(4'-((2-부틸-5-((3-(2-메톡시에틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-yl)-1,2,4-옥사다이아졸-5(4H)-온; 6) 3-(4'-((2-butyl-5-((3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

7) 3-(4'-((2-부틸-5-((3-이소프로필-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 7) 3-(4'-((2-butyl-5-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

8) 3-(4'-((2-부틸-5-((3-(다이메틸아미노)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 8) 3-(4'-((2-butyl-5-((3-(dimethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

9) 3-(4'-((2-부틸-5-((3-((다이메틸아미노)메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 9) 3-(4'-((2-butyl-5-((3-((dimethylamino)methyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

10) 3-(4'-((2-부틸-5-((3-(다이에틸아미노)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 10) 3-(4'-((2-butyl-5-((3-(diethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

11) 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 11) 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxophy Rimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

12) 3-(4'-((2-부틸-5-((3-(2-메톡시프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 12) 3-(4'-((2-butyl-5-((3-(2-methoxypropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

13) 3-(4'-((2-부틸-4-이소프로필-5-((3-메틸-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 13) 3-(4'-((2-butyl-4-isopropyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

14) 3-(4'-((2-부틸-4-메틸-5-((3-메틸-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 14) 3-(4'-((2-butyl-4-methyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

15) 3-(4'-((5-((3-벤질-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 15) 3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

16) 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 16) 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

17) 3-(4'-((5-((3-벤질-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 17) 3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-isopropyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

18) 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 18) 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

19) 3-(4'-((2-부틸-4-메틸-5-((3-(1-메틸사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 19) 3-(4'-((2-butyl-4-methyl-5-((3-(1-methylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

20) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(스파이로[2.2]펜탄-1-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 20) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(spyro[2.2]pentan-1-yl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

21) 3-(4'-((2-부틸-5-((3-(이소프로폭시메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 21) 3-(4'-((2-butyl-5-((3-(isopropoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

22) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(1-페닐사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 22) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclopropyl)-1,2,4-oxadiazol-5-yl) Methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

23) 3-(4'-((2-부틸-5-((3-(3-클로로피리딘-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 23) 3-(4'-((2-butyl-5-((3-(3-chloropyridin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

24) 3-(4'-((2-부틸-5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 24) 3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

25) 3-(4'-((2-부틸-5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 25) 3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

26) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2-페닐프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 26) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-phenylpropan-2-yl)-1,2,4-oxadiazole-5 -Yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

27) 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸-d2)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 27) 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

28) 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸-d2)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 28) 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

29) 3-(4'-((2-부틸-4-메틸-5-((3-(4-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 29) 3-(4'-((2-butyl-4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

30) 3-(4'-((2-부틸-5-((3-(4-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 30) 3-(4'-((2-butyl-5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

31) 3-(4'-((2-부틸-5-((3-(4-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 31) 3-(4'-((2-butyl-5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

32) 3-(4'-((2-부틸-5-((3-(3-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 32) 3-(4'-((2-butyl-5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

33) 3-(4'-((2-부틸-5-((3-(3,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 33) 3-(4'-((2-butyl-5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

34) 3-(4'-((5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 34) 3-(4'-((5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

35) 3-(4'-((5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 35) 3-(4'-((5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

36) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(피페리딘-1-일메틸)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 36) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazole-5 -Yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

37) 3-(4'-((4-메틸-5-((3-(4-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 37) 3-(4'-((4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

38) 3-(4'-((5-((3-(4-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 38) 3-(4'-((5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

39) 3-(4'-((5-((3-(4-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 39) 3-(4'-((5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

40) 3-(4'-((5-((3-(3-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 40) 3-(4'-((5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

41) 3-(4'-((5-((3-(3,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 41) 3-(4'-((5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

42) 3-(4'-((5-((3-(2,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 42) 3-(4'-((5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

43) 3-(4'-((5-((3-사이클로펜틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 43) 3-(4'-((5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

44) 3-(4'-((5-((3-(사이클로펜틸메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 44) 3-(4'-((5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propyl Pyrimidine-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

45) 3-(4'-((5-((3-(사이클로헥실메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 45) 3-(4'-((5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propyl Pyrimidine-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

46) 3-(4'-((2-부틸-5-((3-(2,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 46) 3-(4'-((2-butyl-5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

47) 3-(4'-((2-부틸-5-((3-(사이클로헥실메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-yl)-1,2,4-옥사다이아졸-5(4H)-온; 47) 3-(4'-((2-butyl-5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

48) 3-(4'-((2-부틸-5-((3-(사이클로펜틸메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 48) 3-(4'-((2-butyl-5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

49) 3-(4'-((2-부틸-5-((3-사이클로펜틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 49) 3-(4'-((2-butyl-5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

50) 3-(4'-((5-((3-(사이클로프로필메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 50) 3-(4'-((5-((3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propyl Pyrimidine-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

51) 3-(4'-((5-((3-(2-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 51) 3-(4'-((5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

52) 3-(4'-((5-((3-(3,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 52) 3-(4'-((5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

53) 3-(4'-((5-((3-(2,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 53) 3-(4'-((5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

54) 3-(4'-((5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 54) 3-(4'-((5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

55) 3-(4'-((5-((3-(4-브로모벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 55) 3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

56) 3-(4'-((5-((3-(3-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 56) 3-(4'-((5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

57) 3-(4'-((5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 57) 3-(4'-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

58) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(2,4,6-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 58) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

59) 3-(4'-((4-메틸-6-옥소-5-((3-(피페리딘-1-일)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 59) 3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-yl)-1,2,4-oxadiazol-5-yl)methyl) -2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

60) 3-(4'-((5-((3-사이클로헥실-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 60) 3-(4'-((5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

61) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 61) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

62) 3-(4'-((2-부틸-4-메틸-5-((3-(2-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 62) 3-(4'-((2-butyl-4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

63) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(3-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 63) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

64) 3-(4'-((2-부틸-5-((3-(2,3-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 64) 3-(4'-((2-butyl-5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

65) 3-(4'-((4-메틸-6-옥소-5-((3-(피페리딘-1-일메틸)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 65) 3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl )-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

66) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(3-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 66) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

67) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(4-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 67) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

68) 3-(4'-((5-((3-(1-(4-플루오로페닐)사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 68) 3-(4'-((5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

69) 3-(4'-((4-메틸-5-((3-(몰폴리노메틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 69) 3-(4'-((4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

70) 3-(4'-((4-메틸-6-옥소-5-((3-(1-페닐사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 70) 3-(4'-((4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

71) 3-(4'-((2-부틸-5-((3-(2,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 71) 3-(4'-((2-butyl-5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

72) 3-(4'-((2-부틸-5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 72) 3-(4'-((2-butyl-5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

73) 3-(4'-((2-부틸-5-((3-(2-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 73) 3-(4'-((2-butyl-5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

74) 3-(4'-((2-부틸-5-((3-(2,6-다이클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 74) 3-(4'-((2-butyl-5-((3-(2,6-dichlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

75) 3-(4'-((4-메틸-5-((3-(2-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 75) 3-(4'-((4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

76) 3-(4'-((5-((3-(2,3-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 76) 3-(4'-((5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

77) 3-(4'-((5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 77) 3-(4'-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

78) 3-(4'-((5-((3-(3-클로로-5-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 78) 3-(4'-((5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

79) 3-(4'-((5-((3-(4-브로모벤질)-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 79) 3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

80) 3-(4'-((2-부틸-5-((3-(3-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 80) 3-(4'-((2-butyl-5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

81) 3-(4'-((2-부틸-5-((3-(3,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 81) 3-(4'-((2-butyl-5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

82) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(4-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 82) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

83) 3-(4'-((2-부틸-5-((3-(1-(4-플루오로페닐)사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 83) 3-(4'-((2-butyl-5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl) -4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

84) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(1-페닐사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 84) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl) Methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

85) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(2-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 85) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

86) 3-(4'-((5-((3-(1-(3-플루오로페닐)사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 86) 3-(4'-((5-((3-(1-(3-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

87) 3-(4'-((5-((3-(2-클로로-4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 87) 3-(4'-((5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)vinyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

88) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(3,4,5-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 88) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

89) 3-(4'-((2-부틸-4-메틸-5-((3-(몰폴리노메틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 89) 3-(4'-((2-butyl-4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

90) 3-(4'-((2-부틸-4-메틸-5-((3-(3-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 90) 3-(4'-((2-butyl-4-methyl-5-((3-(3-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

91) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2,4,6-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 91) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

92) 3-(4'-((2-부틸-5-((3-사이클로헥실-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 92) 3-(4'-((2-butyl-5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

93) 3-(4'-((5-((3-(2-클로로-6-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 93) 3-(4'-((5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

94) 3-(4'-((4-메틸-5-((3-(2-메틸펜탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸l)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 94) 3-(4'-((4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyll)-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

95) 3-(4'-((2-부틸-5-((3-(3-클로로-5-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 95) 3-(4'-((2-butyl-5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

96) 3-(4'-((2-부틸-5-((3-사이클로프로필-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 96) 3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

97) 3-(4'-((2-부틸-5-((3-(2-클로로-6-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 97) 3-(4'-((2-butyl-5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

98) 3-(4'-((2-부틸-5-((3-(2-클로로-4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 98) 3-(4'-((2-butyl-5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

99) 3-(4'-((2-부틸-4-메틸-5-((3-(2-메틸펜탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 99) 3-(4'-((2-butyl-4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyl )-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

100) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(3,4,5-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 100) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

101) 3-(4'-((5-((3-(1-(2-클로로페닐)에틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 101) 3-(4'-((5-((3-(1-(2-chlorophenyl)ethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

102) 3-(4'-((2-부틸-5-((3-(2-사이클로헥실프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 102) 3-(4'-((2-butyl-5-((3-(2-cyclohexylpropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

103) 3-(4'-((2-부틸-5-((3-(2-(4-클로로-2-플루오로페닐)프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 103) 3-(4'-((2-butyl-5-((3-(2-(4-chloro-2-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole -5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H) -On;

104) 3-(4'-((2-부틸-5-((3-(2-(2-클로로-6-플루오로페닐)프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 104) 3-(4'-((2-butyl-5-((3-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole -5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H) -On;

105) 3-(4'-((2-부틸-5-((3-(3-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 105) 3-(4'-((2-butyl-5-((3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

106) 3-(4'-((2-부틸-5-((3-(2-메톡시페닐)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 106) 3-(4'-((2-butyl-5-((3-(2-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

107) 3-(4'-((2-부틸-5-((3-(2-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 107) 3-(4'-((2-butyl-5-((3-(2-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

108) 3-(4'-((2-부틸-4-메틸-5-((3-(나프탈렌-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 108) 3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

109) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(테트라하이드로-2H-피란-4-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 109) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(tetrahydro-2H-pyran-4-yl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

110) 3-(4'-((2-부틸-5-((3-(1-에틸사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 110) 3-(4'-((2-butyl-5-((3-(1-ethylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

111) 3-(4'-((2-부틸-5-((3-사이클로부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 111) 3-(4'-((2-butyl-5-((3-cyclobutyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

112) 3-(4'-((5-((3-(바이사이클로[2.2.1]헵탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 112) 3-(4'-((5-((3-(bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-2- Butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

113) 3-(4'-((2-부틸-4-메틸-5-((3-(1-메틸사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 113) 3-(4'-((2-butyl-4-methyl-5-((3-(1-methylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

114) 3-(4'-((2-부틸-4-메틸-5-((3-(나프탈렌-1-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 114) 3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-1-yl)-1,2,4-oxadiazol-5-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

115) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(퀴놀린-2-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 115) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl) Methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

116) 3-(4'-((2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 116) 3-(4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyriimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

117) 3-(4'-((2-부틸-4-메틸-5-((5-(1-메틸사이클로프로필)-1,2,4-옥사다이아졸-3-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 117) 3-(4'-((2-butyl-4-methyl-5-((5-(1-methylcyclopropyl)-1,2,4-oxadiazol-3-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

118) 3-(4'-((2-부틸-5-((5-사이클로프로필-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 118) 3-(4'-((2-butyl-5-((5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

119) 3-(4'-((2-부틸-5-((5-이소프로필-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 119) 3-(4'-((2-butyl-5-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

120) 3-(4'-((2-부틸-5-((5-(1-(4-클로로페닐)사이클로프로필)-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 120) 3-(4'-((2-butyl-5-((5-(1-(4-chlorophenyl)cyclopropyl)-1,2,4-oxadiazol-3-yl)methyl)- 4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

121) 3-(4'-((2-부틸-5-((5-사이클로부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 121) 3-(4'-((2-butyl-5-((5-cyclobutyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

122) 3-(4'-((2-부틸-5-((5-(2-플루오로페닐)-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 122) 3-(4'-((2-butyl-5-((5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

123) 3-(4'-((2-부틸-5-((5-(2-플루오로벤질)-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 123) 3-(4'-((2-butyl-5-((5-(2-fluorobenzyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

124) 4'-((2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-카르복실산; 124) 4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidine-1 (6H)-yl)methyl)biphenyl-2-carboxylic acid;

125) 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온; 125) 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-tert-butyl-1,2,4-oxa Diazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one;

126) 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-(2-플루오로페닐)-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온; 126) 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(2-fluorophenyl)-1,2 ,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one;

127) 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-(4-메톡시벤질)-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온; 127) 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(4-methoxybenzyl)-1,2 ,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one;

128) 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-(4-클로로벤질)-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온; 128) 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(4-chlorobenzyl)-1,2, 4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one;

129) 메틸 4'-((2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-카르복실레이트; 129) Methyl 4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidine- 1(6H)-yl)methyl)biphenyl-2-carboxylate;

130) 3-(4'-((2-부틸-4-이소프로필-5-((5-메틸-1,3,4-옥사다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 130) 3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

131) 3-(4'-((2-부틸-4-이소프로필-5-((5-(4-메톡시페닐)-1,3,4-옥사다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 131) 3-(4'-((2-butyl-4-isopropyl-5-((5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

132) 3-(4'-((2-부틸-4-이소프로필-5-((5-(3-메톡시페닐)-1,3,4-옥사다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 132) 3-(4'-((2-butyl-4-isopropyl-5-((5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

133) 3-(4'-((2-부틸-5-((5-하이드록시-1,3,4-옥사다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 133) 3-(4'-((2-butyl-5-((5-hydroxy-1,3,4-oxadiazol-2-yl)methyl)-4-isopropyl-6-oxopyriimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

134) 3-(4'-((2-부틸-5-((5-(다이메틸아미노)-1,3,4-옥사다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 134) 3-(4'-((2-butyl-5-((5-(dimethylamino)-1,3,4-oxadiazol-2-yl)methyl)-4-isopropyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

135) 3-(4'-((2-부틸-4-이소프로필-6-옥소-5-((5-(피롤리딘-1-일)-1,3,4-옥사다이아졸-2-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 135) 3-(4'-((2-butyl-4-isopropyl-6-oxo-5-((5-(pyrrolidin-1-yl)-1,3,4-oxadiazole-2 -Yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

136) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((5-페닐옥사졸-2-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 136) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((5-phenyloxazol-2-yl)methyl)pyrimidin-1(6H)-yl)methyl) Biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

137) 3-(4'-((5-(벤조[d]옥사졸-2-일메틸)-2-부틸-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 137) 3-(4'-((5-(benzo[d]oxazol-2-ylmethyl)-2-butyl-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl )Biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

138) 3-(4'-((5-((5-벤질이소옥사졸-3-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 138) 3-(4'-((5-((5-benzylisooxazol-3-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl )Biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

139) 3-(4'-((2-부틸-5-((5-터트-부틸이소옥사졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 139) 3-(4'-((2-butyl-5-((5-tert-butylisooxazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl )Methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

140) 3-(4'-((2-부틸-5-((5-(2-하이드록시프로판-2-일)이소옥사졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일l)-1,2,4-옥사다이아졸-5(4H)-온; 140) 3-(4'-((2-butyl-5-((5-(2-hydroxypropan-2-yl)isooxazol-3-yl)methyl)-4-methyl-6-oxopy Rimidine-1(6H)-yl)methyl)biphenyl-2-yll)-1,2,4-oxadiazole-5(4H)-one;

141) 3-(4'-((2-부틸-5-((5-(1-하이드록시에틸)이소옥사졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 141) 3-(4'-((2-butyl-5-((5-(1-hydroxyethyl)isooxazol-3-yl)methyl)-4-methyl-6-oxopyrimidine-1 (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

142) 3-(4'-((2-부틸-4-메틸-5-((5-메틸-1,3,4-싸이아다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 142) 3-(4'-((2-butyl-4-methyl-5-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

143) 3-(4'-((2-부틸-5-((5-에틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 143) 3-(4'-((2-butyl-5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

144) 3-(4'-((2-부틸-5-((5-이소프로필-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 144) 3-(4'-((2-butyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyriimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

145) 3-(4'-((2-부틸-5-((5-터트-부틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 145) 3-(4'-((2-butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopy Rimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

146) 3-(4'-((4-메틸-5-((5-(1-메틸사이클로프로필)-1,3,4-싸이아다이아졸-2-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 146) 3-(4'-((4-methyl-5-((5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl)methyl)-6-oxo- 2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

147) 3-(4'-((5-((5-사이클로프로필-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 147) 3-(4'-((5-((5-cyclopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

148) 3-(4'-((5-((5-터트-부틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 148) 3-(4'-((5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo-2-propylpyri Midin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

149) 3-(4'-((2-부틸-5-((5-터트-부틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 149) 3-(4'-((2-butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

150) 3-(4'-((2-부틸-5-((5-(3-플루오로페닐)-1,3,4-싸이아다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 150) 3-(4'-((2-butyl-5-((5-(3-fluorophenyl)-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

151) 3-(4'-((2-부틸-4-이소프로필-5-((5-메틸-1,3,4-싸이아다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 151) 3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyriimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

152) 3-(4'-((2-부틸-5-((5-에틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 152) 3-(4'-((2-butyl-5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-oxopyriimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

153) 3-(4'-((2-부틸-4-이소프로필-5-((5-이소프로필-1,3,4-싸이아다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 153) 3-(4'-((2-butyl-4-isopropyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopy Rimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

154) 3-(4'-((2-부틸-5-((5-(4-플루오로페닐)-4H-1,2,4-트리아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 154) 3-(4'-((2-butyl-5-((5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4-methyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

155) 3-(4'-((2-부틸-5-((5-(2-플루오로페닐)-4H-1,2,4-트리아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 155) 3-(4'-((2-butyl-5-((5-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4-methyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

156) 3-(4'-((2-부틸-4-메틸-5-((3-메틸-1H-1,2,4-트리아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 156) 3-(4'-((2-butyl-4-methyl-5-((3-methyl-1H-1,2,4-triazol-5-yl)methyl)-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

157) 3-(4'-((2-부틸-4-메틸-5-((3-메틸-1-페닐-1H-1,2,4-트리아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 157) 3-(4'-((2-butyl-4-methyl-5-((3-methyl-1-phenyl-1H-1,2,4-triazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

158) 3-(4'-((2-부틸-5-((1-부틸-3-메틸-1H-1,2,4-트리아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 158) 3-(4'-((2-butyl-5-((1-butyl-3-methyl-1H-1,2,4-triazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;

159) 3-(4'-((2-부틸-5-((1-(4-플루오로벤질)-1H-1,2,3-트리아졸-4-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 및159) 3-(4'-((2-butyl-5-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one; And

160) 3-(4'-((2-부틸-5-((1-(2-플루오로벤질)-1H-1,2,3-트리아졸-4-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온.160) 3-(4'-((2-butyl-5-((1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl- 6-Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one.

본 발명에서, 약제학적으로 허용가능한 염은 의약업계에서 통상적으로 사용되는 염을 의미하며, 예를 들어 칼슘, 포타슘, 소듐 및 마그네슘 등으로 제조된 무기이온염, 염산, 질산, 인산, 브롬산, 요오드산, 과염소산 및 황산 등으로 제조된 무기산염; 아세트산, 트라이플루오로아세트산, 시트르산, 말레인산, 숙신산, 옥살산, 벤조산, 타르타르산, 푸마르산, 만데르산, 프로피온산, 젖산, 글리콜산, 글루콘산, 갈락투론산, 글루탐산, 글루타르산, 글루쿠론산, 아스파르트산, 아스코르브산, 카본산, 바닐릭산, 하이드로 아이오딕산 등으로 제조된 유기산염; 메탄설폰산, 에탄설폰산, 벤젠설폰산, p-톨루엔설폰산 및 나프탈렌설폰산 등으로 제조된 설폰산염; 글리신, 아르기닌, 라이신 등으로 제조된 아미노산염; 및 트리메틸아민, 트라이에틸아민, 암모니아, 피리딘, 피콜린 등으로 제조된 아민염 등이 있으나, 열거된 이들 염에 의해 본 발명에서 의미하는 염의 종류가 한정되는 것은 아니다.In the present invention, the pharmaceutically acceptable salt means a salt commonly used in the pharmaceutical industry, for example, inorganic ionic salts made of calcium, potassium, sodium and magnesium, hydrochloric acid, nitric acid, phosphoric acid, bromic acid, Inorganic acid salts made of iodic acid, perchloric acid and sulfuric acid; Acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid Organic acid salts made of acid, ascorbic acid, carbonic acid, vanic acid, and hydroiodic acid; Sulfonic acid salts made of methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and naphthalenesulfonic acid; Amino acid salts made of glycine, arginine, lysine, etc.; And amine salts made of trimethylamine, triethylamine, ammonia, pyridine, picoline, and the like, but the types of salts in the present invention are not limited by the salts listed.

본 발명의 화학식 I 로 표시되는 화합물은 1 개 이상의 비대칭 탄소를 함유할 수 있으며, 이에 따라 라세미체, 라세믹 혼합물, 단일의 에난티오머, 부분입체이성체 혼합물 및 각각의 부분입체이성체로서 존재할 수 있다. 이러한 이성질체는 종래기술, 예를 들어 화학식 I 로 표시된 화합물은 관 크로마토그래피 또는 HPLC 등의 분할에 의해 분리가 가능하다. 또는, 화학식 I 로 표시되는 화합물 각각의 입체 이성질체는 공지된 배열의 광학적으로 순수한 출발 물질 및/또는 시약을 사용하여 입체 특이적으로 합성할 수 있다. The compounds represented by formula (I) of the present invention may contain one or more asymmetric carbons, and thus may exist as racemates, racemic mixtures, single enantiomers, diastereomeric mixtures and respective diastereomers. have. These isomers can be separated by the prior art, for example, a compound represented by the formula (I) by column chromatography or HPLC. Alternatively, the stereoisomers of each of the compounds represented by the formula (I) can be stereospecifically synthesized using a known arrangement of optically pure starting materials and/or reagents.

화학식 I 화합물의 제조방법Method for preparing compound of formula I

본 발명은 화학식 I 로 표시되는 화합물, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염의 제조방법을 제공한다.The present invention provides a method for preparing a compound represented by Formula I, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

본 발명에 있어서, 본 발명의 화학식 I 로 표시되는 화합물, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염은 하기 반응식 1의 경로에 따라 제조할 수 있다.In the present invention, the compound represented by the formula (I) of the present invention, an optical isomer thereof or a pharmaceutically acceptable salt thereof can be prepared according to the route of Scheme 1 below.

[반응식 1][Scheme 1]

Figure 112018068967010-pat00031
Figure 112018068967010-pat00031

구체적으로, 상업적으로 구입가능한 화학식 1의 화합물 및 화학식 2의 화합물을 출발물질로 하여 염기 조건 하에 중합 반응을 통하여 화학식 3의 화합물을 얻고, 이와 화학식 4의 아미딘 화합물의 고리형성 반응을 통해 화학식 5의 화합물을 얻는다. 이를 화학식 6의 화합물과 염기를 이용한 중합반응을 통해 화학식 7의 화합물을 얻고 이의 시아노기를 공지된 방법으로 옥사다이아졸론으로 변형하여 화학식 11의 화합물을 얻는다. 화학식 11의 화합물을 가수분해한 뒤 여러가지 옥심화합물, 아미딘화합물 또는 히드라진화합물 등과 반응하고 고리화 반응을 통하여 화학식 I의 화합물을 제조할 수 있다.Specifically, a commercially available compound of Formula 1 and Compound 2 are used as starting materials to obtain a compound of Formula 3 through a polymerization reaction under basic conditions, and thus, through a ring-forming reaction of an amidine compound of Formula 4 To obtain the compound. This is obtained through the polymerization reaction using the compound of Formula 6 and a base, and the cyano group thereof is transformed into oxadiazolone by a known method to obtain a compound of Formula 11. After hydrolyzing the compound of Formula 11, it can react with various oxime compounds, amidine compounds, or hydrazine compounds, and prepare a compound of Formula I through a cyclization reaction.

보다 구체적으로, 본 발명의 화학식 I 로 표시되는 화합물, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염은 하기 반응식 2 내지 9의 경로에 따라 제조할 수 있다.More specifically, the compound represented by the formula (I) of the present invention, an optical isomer thereof, or a pharmaceutically acceptable salt thereof may be prepared according to the following schemes 2 to 9.

[반응식 2][Scheme 2]

Figure 112018068967010-pat00032
Figure 112018068967010-pat00032

[반응식 3][Scheme 3]

Figure 112018068967010-pat00033
Figure 112018068967010-pat00033

[반응식 4][Scheme 4]

Figure 112018068967010-pat00034
Figure 112018068967010-pat00034

[반응식 5][Scheme 5]

Figure 112018068967010-pat00035
Figure 112018068967010-pat00035

[반응식 6][Scheme 6]

Figure 112018068967010-pat00036
Figure 112018068967010-pat00036

[반응식 7][Scheme 7]

Figure 112018068967010-pat00037
Figure 112018068967010-pat00037

[반응식 8][Scheme 8]

Figure 112018068967010-pat00038
Figure 112018068967010-pat00038

[반응식 9][Scheme 9]

Figure 112018068967010-pat00039
Figure 112018068967010-pat00039

화학식 I 화합물을 포함하는 조성물, 이의 용도 및 이를 이용한 치료방법Composition comprising a compound of formula I, use thereof and method of treatment using same

본 발명은 하기 화학식 I 로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 고혈압 또는 당뇨병의 치료 또는 예방용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for the treatment or prevention of hypertension or diabetes, comprising a compound represented by the formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

[화학식 I][Formula I]

Figure 112018068967010-pat00040
Figure 112018068967010-pat00040

상기 화학식 I 은 위에서 정의한 바와 같다.Formula I is as defined above.

본 발명에 있어서, 상기 고혈압은 본태성 고혈압일 수 있고, 상기 당뇨병은 제2형 당뇨병일 수 있다.In the present invention, the hypertension may be essential hypertension, and the diabetes may be type 2 diabetes.

본 발명의 일 구체예에 따르면, 본 발명의 화합물은 고혈압 및 당뇨병 모두에 대하여 약리활성을 나타낸다. 따라서, 본 발명의 약학적 조성물은 고혈압 및 당뇨병을 동시에 치료 또는 예방하기 위하여 유용하게 사용될 수 있다.According to one embodiment of the invention, the compounds of the invention exhibit pharmacological activity against both hypertension and diabetes. Therefore, the pharmaceutical composition of the present invention can be usefully used to simultaneously treat or prevent hypertension and diabetes.

본 발명의 약학적 조성물은 투여를 위해서 상기 화학식 I 로 표시되는 화합물, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염 외에 추가로 약제학적으로 허용가능한 담체를 1 종 이상 더 포함할 수 있다. 약제학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 따라서, 본 발명의 조성물은 패치제, 액제, 환약, 캡슐, 과립, 정제, 좌제 등일 수 있다. 이들 제제는 당 분야에서 제제화에 사용되는 통상의 방법 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA 에 개시되어 있는 방법으로 제조될 수 있으며 각 질환에 따라 또는 성분에 따라 다양한 제제로 제제화될 수 있다.For administration, the pharmaceutical composition of the present invention may further include at least one pharmaceutically acceptable carrier in addition to the compound represented by the formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable carriers can be used by mixing one or more of these components: saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and, if necessary, antioxidants, buffers , Other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable formulations such as aqueous solutions, suspensions, emulsions, pills, capsules, granules or tablets. Therefore, the composition of the present invention may be a patch, liquid, pill, capsule, granule, tablet, suppository, and the like. These formulations can be prepared by conventional methods used in the formulation in the art or by methods disclosed in Remington's Pharmaceutical Science (latest edition), Mack Publishing Company, Easton PA, and formulated into various formulations according to each disease or component. Can be.

본 발명의 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도 등에 따라 그 범위가 다양하다. 본 발명의 화학식 I 로 표시되는 화합물의 일일 투여량은 약 1 내지 1000 ㎎/㎏ 이고, 바람직하게는 5 내지 100 ㎎/㎏ 이며, 하루 일회 내지 수회에 나누어 투여할 수 있다. The composition of the present invention may be administered orally or parenterally (eg, intravenously, subcutaneously, intraperitoneally, or topically) according to the desired method, and the dosage is the patient's weight, age, sex, and health status , The range varies according to diet, administration time, administration method, excretion rate and disease severity. The daily dosage of the compound represented by the formula (I) of the present invention is about 1 to 1000 mg/kg, preferably 5 to 100 mg/kg, and can be divided and administered once to several times a day.

본 발명의 상기 약학적 조성물은 상기 화학식 I 로 표시되는 화합물, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염 외에 동일 또는 유사한 약효를 나타내는 유효성분을 1 종 이상 더 포함할 수 있다. The pharmaceutical composition of the present invention may further include at least one active ingredient exhibiting the same or similar medicinal effect, in addition to the compound represented by the formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

본 발명은 상기 화학식 I 로 표시되는 화합물, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염의 치료학적으로 유효한 양을 인간을 포함하는 포유류에 투여하는 단계를 포함하는, 고혈압 또는 당뇨병을 치료하는 방법을 제공한다. The present invention provides a method for treating hypertension or diabetes, comprising administering to a mammal, including a human, a therapeutically effective amount of a compound represented by Formula I, an optical isomer thereof, or a pharmaceutically acceptable salt thereof. do.

본 발명에서 사용되는 "치료학적으로 유효한 양"이라는 용어는 고혈압 또는 당뇨병의 치료에 유효한 상기 화학식 I 로 표시되는 화합물의 양을 나타낸다.The term "therapeutically effective amount" used in the present invention refers to the amount of the compound represented by the formula (I) effective in the treatment of hypertension or diabetes.

본 발명의 치료방법은 상기 화학식 I 로 표시되는 화합물을 투여함으로써, 징후의 발현 전에 질병 그 자체를 다룰 뿐만 아니라, 이의 징후를 저해하거나 피하는 것을 또한 포함한다. 질환의 관리에 있어서, 특정 활성 성분의 예방적 또는 치료학적 용량은 질병 또는 상태의 본성(nature)과 심각도, 그리고 활성 성분이 투여되는 경로에 따라 다양할 것이다. 용량 및 용량의 빈도는 개별 환자의 연령, 체중 및 반응에 따라 다양할 것이다. 적합한 용량 용법은 이러한 인자를 당연히 고려하는 이 분야의 통상의 지식을 가진 자에 의해 쉽게 선택될 수 있다. 또한, 본 발명의 치료방법은 상기 화학식 I 로 표시되는 화합물과 함께 질환 치료에 도움이 되는 추가적인 활성 제제의 치료학적으로 유효한 양의 투여를 더 포함할 수 있으며, 추가적인 활성제제는 상기 화학식 I 의 화합물과 함께 시너지 효과 또는 보조적 효과를 나타낼 수 있다.The treatment method of the present invention includes not only treating the disease itself before the manifestation of the manifestation, but also inhibiting or avoiding the manifestation thereof, by administering the compound represented by the formula (I). In the management of a disease, the prophylactic or therapeutic dose of a particular active ingredient will vary depending on the nature and severity of the disease or condition and the route the active ingredient is administered. The dose and frequency of dose will vary depending on the age, weight and response of the individual patient. Suitable dosage regimens can be readily selected by those of ordinary skill in the art taking these factors into account. In addition, the treatment method of the present invention may further include the administration of a therapeutically effective amount of an additional active agent conducive to the treatment of a disease together with the compound represented by the formula (I), the additional active agent is a compound of the formula (I) In addition, it may have a synergistic effect or an auxiliary effect.

본 발명은 또한 고혈압 또는 당뇨병의 치료용 약제의 제조를 위한 상기 화학식 I 로 표시되는 화합물, 이의 광학 이성질체 또는 이의 약제학적으로 허용가능한 염의 용도를 제공하고자 한다. 약제의 제조를 위한 상기 화학식 I 로 표시되는 화합물은 허용되는 보조제, 희석제, 담체 등을 혼합할 수 있으며, 기타 활성제제와 함께 복합 제제로 제조되어 활성 성분들의 상승 작용을 가질 수 있다. The present invention also seeks to provide the use of a compound represented by the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of hypertension or diabetes. The compound represented by the formula (I) for the manufacture of a medicament may be mixed with an acceptable adjuvant, diluent, carrier, etc., and may be synergistically active with other active agents.

본 발명의 조성물, 용도, 치료방법에서 언급된 사항은 서로 모순되지 않는 한 동일하게 적용된다.The matters mentioned in the compositions, uses, and treatment methods of the present invention apply equally unless there are contradictions.

본 발명의 피리미디논 유도체 화합물은 고혈압 및/또는 당뇨병의 치료 활성을 나타낸다.The pyrimidinone derivative compound of the present invention exhibits therapeutic activity for hypertension and/or diabetes.

이하, 하기 실시예 및 실험예를 들어 본 발명을 더욱 구체적으로 설명한다. 그러나 이들 실시예 및 실험예는 본 발명에 대한 이해를 돕기 위해 예시의 목적으로만 제공된 것일 뿐 본 발명의 범위가 하기 실시예 및 실험예에 의해 제한되는 것은 아니다. Hereinafter, the present invention will be described in more detail with reference to the following examples and experimental examples. However, these examples and experimental examples are provided for the purpose of illustration only to aid understanding of the present invention, and the scope of the present invention is not limited by the following examples and experimental examples.

실시예Example A-1: 3-(4'-((2-부틸-5-((3-(2- A-1: 3-(4'-((2-butyl-5-((3-(2- 플루오로페닐Fluorophenyl )-1,2,4-)-1,2,4- 옥사다이아졸Oxadiazole -5-일)-5 days) 메틸methyl )-4-)-4- 메틸methyl -6--6- 옥소피리미딘Oxopyrimidine -1(6H)-일)-1(6H)-day) 메틸methyl )) 바이페닐Biphenyl -2-일)-1,2,4--2-day)-1,2,4- 옥사다이Oksada 아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Azole-5(4H)-one {3-(4'-((2-butyl-5-((3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Preparation of methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

[단계 1] (Z)-2-플루오로-N'-하이드록시벤즈이미드아마이드 {(Z)-2-fluoro-N'-hydroxybenzimidamide}의 제조[Step 1] Preparation of (Z)-2-fluoro-N'-hydroxybenzimideamide {(Z)-2-fluoro-N'-hydroxybenzimidamide}

Figure 112018068967010-pat00041
Figure 112018068967010-pat00041

플라스크에 NH2OH.HCl (688 mg, 9.9 mmol), NaHCO3 (832 mg, 9.9 mmol)을 넣고 정제수 5 ml를 주입 후 교반하였다. 2-플루오로 벤조나이트릴 (1 g, 8.26 mmol)을 에탄올 10 ml에 녹여서 플라스크에 주입한 후, 12 시간 동안 환류 교반하였다. 상온으로 냉각 후 반응액을 농축하였다. 에틸아세테이트 30 ml를 주입하고, 포화 NaHCO3 30 ml로 세척하였다. MgSO4로 건조하여 여과한 후, 여액을 농축하였다. 제조된 표제 화합물 (1.14 g)은 별도의 정제 없이 다음 반응에 사용하였다.NH 2 OH.HCl (688 mg, 9.9 mmol) and NaHCO 3 (832 mg, 9.9 mmol) were added to the flask, and 5 ml of purified water was injected and stirred. 2-fluoro benzonitrile (1 g, 8.26 mmol) was dissolved in 10 ml of ethanol, injected into a flask, and stirred at reflux for 12 hours. After cooling to room temperature, the reaction solution was concentrated. 30 ml of ethyl acetate was injected and washed with 30 ml of saturated NaHCO 3 . After drying over MgSO 4 and filtering, the filtrate was concentrated. The title compound (1.14 g) prepared was used in the next reaction without further purification.

[단계 2] 3-(4'-((2-부틸-5-((3-(2-플루오로페닐)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조[Step 2] 3-(4'-((2-butyl-5-((3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl- Preparation of 2-yl)-1,2,4-oxadiazol-5(4H)-one}

Figure 112018068967010-pat00042
Figure 112018068967010-pat00042

플라스크에 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세트산 (50 mg, 0.105 mmol)을 넣은 후, 피리딘 1 ml를 넣었다. SOCl2 15 mg를 주입한 후, 상온에서 1 시간 동안 교반하였다. 미리 준비된 단계 1의 화합물 (20 mg 0.126 mmol)을 주입한 후, 12 시간 동안 환류 교반하였다. 반응액을 농축한 후, 에틸아세테이트 20 ml를 넣고 정제수 20 ml와 brine 20 ml로 순차적으로 세척하였다. 무수 MgSO4로 유기층을 건조하여 여과한 후, 여액을 농축하였다. Prep-LC (아세토나이트릴 20 내지 100 %, gradient)로 정제하여 표제 화합물 27mg을 수득하였다.2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) in a flask) Biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetic acid (50 mg, 0.105 mmol) was added, followed by 1 ml of pyridine. After injecting SOCl 2 15 mg, the mixture was stirred at room temperature for 1 hour. The compound of step 1 (20 mg 0.126 mmol) prepared in advance was injected, followed by stirring at reflux for 12 hours. After the reaction solution was concentrated, 20 ml of ethyl acetate was added and washed sequentially with 20 ml of purified water and 20 ml of brine. The organic layer was dried over anhydrous MgSO 4 , filtered, and the filtrate was concentrated. Purification by Prep-LC (acetonitrile 20-100%, gradient) gave 27 mg of the title compound.

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.38 (2H, m), 1.67 (2H, m), 2.34 (3H, s), 2.67 (2H, t), 4.14 (2H, s), 5.26 (2H, s), 7.16-7.99 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.38 (2H, m), 1.67 (2H, m), 2.34 (3H, s), 2.67 (2H, t), 4.14 ( 2H, s), 5.26 (2H, s), 7.16-7.99 (12H, m)

<실시예 A-2 내지 A-115><Examples A-2 to A-115>

실시예 A-2 내지 A-115의 화합물은 실시예 A-1과 유사한 방법으로 각 실시예에 대응하는 나이트릴 유도체 화합물을 이용하여 합성하였다.The compounds of Examples A-2 to A-115 were synthesized using a nitrile derivative compound corresponding to each example in a similar manner to Example A-1.

실시예 A-2: 3-(4'-((2-부틸-5-((3-사이클로프로필-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-2: 3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2- butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1 Preparation of ,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97-1.01 (6H, m), 1.18 (6H, d), 1.43 (2H, m), 1.78 (2H, m), 2.05 (1H, m), 2.73 (2H, t), 3.01 (1H, m), 4.20 (2H, s), 5.31 (2H, s), 7.25-7.35 (4H, m), 7.43 (1H, d), 7.54 (1H, t), 7.61 (1H, t), 7.84 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97-1.01 (6H, m), 1.18 (6H, d), 1.43 (2H, m), 1.78 (2H, m), 2.05 (1H, m), 2.73 (2H, t), 3.01 (1H, m), 4.20 (2H, s), 5.31 (2H, s), 7.25-7.35 (4H, m), 7.43 (1H, d), 7.54 (1H, t) , 7.61 (1H, t), 7.84 (1H, d)

실시예 A-3: 3-(4'-((2-부틸-5-((3-사이클로프로필-1,2,4-옥소다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-3: 3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxodiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.92 (3H, t), 0.98-1.02 (4H, m), 1.35-1.74 (4H, m), 1.99-2.04 (1H, m), 2.31 (3H, s), 2.69 (2H, t), 4.03 (2H, s), 5.28 (2H, s), 7.19-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 0.98-1.02 (4H, m), 1.35-1.74 (4H, m), 1.99-2.04 (1H, m), 2.31 (3H , s), 2.69 (2H, t), 4.03 (2H, s), 5.28 (2H, s), 7.19-7.80 (8H, m)

실시예 A-4: 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-4: 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2- butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl) Preparation of -1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.33-1.43 (11H, m), 1.65-1.73 (2H, m), 2.30 (3H, s), 2.67 (2H, t), 4.05 (2H, s), 5,28 (2H, s), 7.18-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.33-1.43 (11H, m), 1.65-1.73 (2H, m), 2.30 (3H, s), 2.67 (2H, t ), 4.05 (2H, s), 5,28 (2H, s), 7.18-7.78 (8H, m)

실시예 A-5: 3-(4'-((2-부틸-5-((3-(메톡시메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-5: 3-(4'-((2-butyl-5-((3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2- Preparation of yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.33-1.71 (4H, m), 2.31 (3H, s), 2.66 (2H, t), 3.42 (3H, s), 4.08 (2H, s), 4.51 (2H, s), 5.24 (2H, s), 7.15-7.74 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.33-1.71 (4H, m), 2.31 (3H, s), 2.66 (2H, t), 3.42 (3H, s), 4.08 (2H, s), 4.51 (2H, s), 5.24 (2H, s), 7.15-7.74 (8H, m)

실시예 A-6: 3-(4'-((2-부틸-5-((3-(2-메톡시에틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-yl)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-6: 3-(4'-((2-butyl-5-((3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.34-1.72 (4H, m), 2.31 (3H, s), 2.67 (2H, t), 2.95 (2H, t), 3.33 (3H, s), 3.73 (2H, t), 4.05 (2H, s), 5.26 (2H, s), 7.17-7.76 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.34-1.72 (4H, m), 2.31 (3H, s), 2.67 (2H, t), 2.95 (2H, t), 3.33 (3H, s), 3.73 (2H, t), 4.05 (2H, s), 5.26 (2H, s), 7.17-7.76 (8H, m)

실시예 A-7: 3-(4'-((2-부틸-5-((3-이소프로필-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one }의 제조Example A-7: 3-(4'-((2-butyl-5-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.92 (3H, t), 1.30 (6H, d), 1.44-1.74 (4H, m), 2.32 (3H, s), 2.69 (2H, t), 3.00-3.07 (1H, m), 4.08 (2H, s), 5.28 (2H, s), 7.20-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 1.30 (6H, d), 1.44-1.74 (4H, m), 2.32 (3H, s), 2.69 (2H, t), 3.00-3.07 (1H, m), 4.08 (2H, s), 5.28 (2H, s), 7.20-7.80 (8H, m)

실시예 A-8: 3-(4'-((2-부틸-5-((3-(다이메틸아미노)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(dimethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-8: 3-(4'-((2-butyl-5-((3-(dimethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((3-(dimethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2- Preparation of yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.34-1.72 (4H, m), 2.30 (3H, s), 2.66 (2H, t), 2.95 (6H, s), 3.91 (2H, s), 5.26 (2H, s), 7.18-7.77 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.34-1.72 (4H, m), 2.30 (3H, s), 2.66 (2H, t), 2.95 (6H, s), 3.91 (2H, s), 5.26 (2H, s), 7.18-7.77 (8H, m)

실시예 A-9: 3-(4'-((2-부틸-5-((3-((다이메틸아미노)메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-((dimethylamino)methyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-9: 3-(4'-((2-butyl-5-((3-((dimethylamino)methyl)-1,2,4-oxadiazol-5-yl)methyl)- 4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-5-((3-((dimethylamino)methyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl) Preparation of methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.92 (3H, t), 1.36-1.76 (4H, m), 2.06 (6H, s), 2.41 (3H, s), 2.72 (2H, t), 3.38 (2H, s), 4.09 (2H, s), 5.23 (2H, s), 6.90-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 1.36-1.76 (4H, m), 2.06 (6H, s), 2.41 (3H, s), 2.72 (2H, t), 3.38 (2H, s), 4.09 (2H, s), 5.23 (2H, s), 6.90-7.80 (8H, m)

실시예 A-10: 3-(4'-((2-부틸-5-((3-(다이에틸아미노)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(diethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-10: 3-(4'-((2-butyl-5-((3-(diethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((3-(diethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2- Preparation of yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.07 (3H, t), 1.30-1.69 (4H, m), 2.36 (3H, s), 2.63 (2H, t), 3.25-3.30 (4H, m), 3.93 (2H, s), 5.21 (2H, s), 6.93-7.67 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.07 (3H, t), 1.30-1.69 (4H, m), 2.36 (3H, s), 2.63 (2H, t), 3.25-3.30 (4H, m), 3.93 (2H, s), 5.21 (2H, s), 6.93-7.67 (8H, m)

실시예 A-11: 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-11: 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2 -butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl )-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.18 (6H, d), 1.33-1.43 (11H, m), 1.65-2.05 (4H, m), 2.67 (2H, t), 3.01 (1H, m), 4.05 (2H, s), 5.27 (2H, s), 7.18-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.18 (6H, d), 1.33-1.43 (11H, m), 1.65-2.05 (4H, m), 2.67 (2H, t ), 3.01 (1H, m), 4.05 (2H, s), 5.27 (2H, s), 7.18-7.78 (8H, m)

실시예 A-12: 3-(4'-((2-부틸-5-((3-(2-메톡시프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-methoxypropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-12: 3-(4'-((2-butyl-5-((3-(2-methoxypropan-2-yl)-1,2,4-oxadiazol-5-yl) Methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-5-((3-(2-methoxypropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1 Preparation of (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, m), 1.23 (3H, d), 1.36 (5H, m), 1.72 (2H, m), 2.34 (3H, s), 2.71 (2H, t), 3.61 (2H, s), 3.74 (3H, s), 5.34 (2H, s), 7.20 (2H, d), 7.34 (2H, d), 7.44 (1H, q), 7.51 (1H, t), 7.62 (1H, t), 7.82 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, m), 1.23 (3H, d), 1.36 (5H, m), 1.72 (2H, m), 2.34 (3H, s), 2.71 ( 2H, t), 3.61 (2H, s), 3.74 (3H, s), 5.34 (2H, s), 7.20 (2H, d), 7.34 (2H, d), 7.44 (1H, q), 7.51 (1H , t), 7.62 (1H, t), 7.82 (1H, d)

실시예 A-13: 3-(4'-((2-부틸-4-이소프로필-5-((3-메틸-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-13: 3-(4'-((2-butyl-4-isopropyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -4-isopropyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.18 (6H, d), 1.32-1.43 (5H, m), 1.65-2.05 (4H, m), 2.67 (2H, t), 3.01 (1H, m), 4.05 (2H, s), 5,27 (2H, s), 7.18-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.18 (6H, d), 1.32-1.43 (5H, m), 1.65-2.05 (4H, m), 2.67 (2H, t ), 3.01 (1H, m), 4.05 (2H, s), 5,27 (2H, s), 7.18-7.78 (8H, m)

실시예 A-14: 3-(4'-((2-부틸-4-메틸-5-((3-메틸-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-14: 3-(4'-((2-butyl-4-methyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl- 4-methyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2 Preparation of ,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.32-1.43 (5H, m), 1.65-2.05 (4H, m), 2.67 (2H, t), 2.75 (3H, s), 4.05 (2H, s), 5,27 (2H, s), 7.18-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.32-1.43 (5H, m), 1.65-2.05 (4H, m), 2.67 (2H, t), 2.75 (3H, s) ), 4.05 (2H, s), 5,27 (2H, s), 7.18-7.78 (8H, m)

실시예 A-15: 3-(4'-((5-((3-벤질-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-15: 3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-(( 3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2 Preparation of ,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91-1.20 (3H, t), 1.38 (2H, m), 1.74 (2H, m), 2.75 (3H, s), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.53 (2H, t), 6.97-7.58 (11H, m), 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91-1.20 (3H, t), 1.38 (2H, m), 1.74 (2H, m), 2.75 (3H, s), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.53 (2H, t), 6.97-7.58 (11H, m),

실시예 A-16: 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-16: 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91-1.20 (3H, t), 1.38 (2H, m), 1.74 (2H, m), 2.75 (3H, s), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.53 (2H, t), 6.97-7.31 (6H, m), 7.36 (1H, d), 7.45 (1H, q), 7.56 (1H, q), 7.62 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91-1.20 (3H, t), 1.38 (2H, m), 1.74 (2H, m), 2.75 (3H, s), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.53 (2H, t), 6.97-7.31 (6H, m), 7.36 (1H, d), 7.45 (1H, q ), 7.56 (1H, q), 7.62 (1H, d)

실시예 A-17: 3-(4'-((5-((3-벤질-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-17: 3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-isopropyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-( (3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91-1.10 (3H, t), 1.18 (6H, d), 1.38 (2H, m), 1.74 (2H, m), 2.70 (2H, t), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.54 (2H, t), 6.98-7.65 (10H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91-1.10 (3H, t), 1.18 (6H, d), 1.38 (2H, m), 1.74 (2H, m), 2.70 (2H, t), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.54 (2H, t), 6.98-7.65 (10H, m)

실시예 A-18: 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-18: 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

1H-NMR (400 MHz, CDCl3): δ 0.91-1.05 (3H, t), 1.18 (6H, d), 1.38 (2H, m), 1.74 (2H, m), 2.70 (2H, t), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.54 (2H, t), 6.98-7.30 (6H, m), 7.36 (1H, d), 7.46 (1H, q), 7.57 (1H, q), 7.62 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91-1.05 (3H, t), 1.18 (6H, d), 1.38 (2H, m), 1.74 (2H, m), 2.70 (2H, t), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.54 (2H, t), 6.98-7.30 (6H, m), 7.36 (1H, d ), 7.46 (1H, q), 7.57 (1H, q), 7.62 (1H, d)

실시예 A-19: 3-(4'-((2-부틸-4-메틸-5-((3-(1-메틸사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(1-methylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-19: 3-(4'-((2-butyl-4-methyl-5-((3-(1-methylcyclopropyl)-1,2,4-oxadiazol-5-yl) Methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-4-methyl-5-((3-(1-methylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 0.98-1.25 (7H, m), 1.35-1.75 (4H, m), 2.31 (3H, s), 2.68 (2H, t, J=8Hz), 4.03 (2H, s), 5.23 (2H, s), 7.18-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 0.98-1.25 (7H, m), 1.35-1.75 (4H, m), 2.31 (3H, s), 2.68 (2H, t , J=8Hz), 4.03 (2H, s), 5.23 (2H, s), 7.18-7.80 (8H, m)

실시예 A-20: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(스파이로[2.2]펜탄-1-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(spiro[2.2]pentan-1-yl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-20: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(spyro[2.2]pentan-1-yl)-1,2,4 -Oxadiazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-4-methyl-6-oxo-5-((3-(spiro[2.2]pentan-1-yl)-1,2,4-oxadiazol-5-yl)methyl) Preparation of pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.75-0.79 (1H, m), 0.87-0.96 (6H, m), 1.31-1.69 (6H, m), 2.26 (3H, s), 2.35-2.38 (1H, m), 2.64 (2H, t), 4.00 (2H, s), 5.24 (2H, s), 7.13-7.71 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.75-0.79 (1H, m), 0.87-0.96 (6H, m), 1.31-1.69 (6H, m), 2.26 (3H, s), 2.35-2.38 (1H, m), 2.64 (2H, t), 4.00 (2H, s), 5.24 (2H, s), 7.13-7.71 (8H, m)

실시예 A-21: 3-(4'-((2-부틸-5-((3-(이소프로폭시메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(isopropoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-21: 3-(4'-((2-butyl-5-((3-(isopropoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((3-(isopropoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2 Preparation of -yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.19 (6H, d), 1.32-1.70 (4H, m), 2.30 (3H, s), 2.66 (2H, t), 3.69-3.78 (1H, m), 4.07 (2H, s), 4.55 (2H, s), 5.24 (2H, s), 7.13-7.72 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.19 (6H, d), 1.32-1.70 (4H, m), 2.30 (3H, s), 2.66 (2H, t), 3.69-3.78 (1H, m), 4.07 (2H, s), 4.55 (2H, s), 5.24 (2H, s), 7.13-7.72 (8H, m)

실시예 A-22: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(1-페닐사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-22: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclopropyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.87 (3H, t), 1.26-1.65 (4H, m), 2.54 (3H, s), 2.62 (2H, t), 5.19 (2H, s), 6.91-7.95 (19H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H, t), 1.26-1.65 (4H, m), 2.54 (3H, s), 2.62 (2H, t), 5.19 (2H, s), 6.91-7.95 (19H, m)

실시예 A-23: 3-(4'-((2-부틸-5-((3-(3-클로로피리딘-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(3-chloropyridin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-23: 3-(4'-((2-butyl-5-((3-(3-chloropyridin-2-yl)-1,2,4-oxadiazol-5-yl)methyl )-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-5-((3-(3-chloropyridin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91-1.15 (3H, t), 1.38 (2H, m), 1.74 (2H, m), 2.75 (3H, s), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.53 (2H, t), 6.97-7.31 (6H, m), 7.36 (1H, d), 7.45 (1H, q), 7.56 (1H, q), 7.62 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91-1.15 (3H, t), 1.38 (2H, m), 1.74 (2H, m), 2.75 (3H, s), 2.94 (1H, m), 3.98 (2H, s,), 4.07 (2H, s), 5.30 (2H, s), 6.53 (2H, t), 6.97-7.31 (6H, m), 7.36 (1H, d), 7.45 (1H, q ), 7.56 (1H, q), 7.62 (1H, d)

실시예 A-24: 3-(4'-((2-부틸-5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-24: 3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.38 (2H, m), 1.69 (2H, m), 2.29 (3H, s), 2.68 (2H, m), 4.00 (2H, s), 4.15 (2H, s), 5.27 (2H, s), 6.96 (2H, m), 6.97-7.30 (6H, m), 7.37 (1H, d), 7.48 (1H, q), 7.60 (1H, q), 7.80 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.38 (2H, m), 1.69 (2H, m), 2.29 (3H, s), 2.68 (2H, m), 4.00 ( 2H, s), 4.15 (2H, s), 5.27 (2H, s), 6.96 (2H, m), 6.97-7.30 (6H, m), 7.37 (1H, d), 7.48 (1H, q), 7.60 (1H, q), 7.80 (1H, d)

실시예 A-25: 3-(4'-((2-부틸-5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-25: 3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

1H-NMR (400 MHz, CDCl3): δ 0.92 (3H, t), 1.18 (6H, d), 1.38 (2H, m), 1.69 (2H, m), 2.68 (2H, m), 2.96 (1H, m), 4.00 (2H, s), 4.15 (2H, s), 5.27 (2H, s), 6.97 (2H, m), 6.97-7.30 (6H, m), 7.37 (1H, d), 7.48 (1H, q), 7.61 (1H, q), 7.80 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 1.18 (6H, d), 1.38 (2H, m), 1.69 (2H, m), 2.68 (2H, m), 2.96 ( 1H, m), 4.00 (2H, s), 4.15 (2H, s), 5.27 (2H, s), 6.97 (2H, m), 6.97-7.30 (6H, m), 7.37 (1H, d), 7.48 (1H, q), 7.61 (1H, q), 7.80 (1H, d)

실시예 A-26: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2-페닐프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-phenylpropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-26: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-phenylpropan-2-yl)-1,2,4-oxa Diazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-(4 '-((2-butyl-4-methyl-6-oxo-5-((3-(2-phenylpropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.38 (2H, m), 1.64 (2H, m), 1.72 (6H, s), 2.20 (3H, s), 2.62 (2H, t), 3.97 (2H, s), 5.23 (2H, s), 7.12-7.28 (9H, m), 7.36 (1H, d), 7.44 (m, 1H), 7.53 (m, 1H), 7.67 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.38 (2H, m), 1.64 (2H, m), 1.72 (6H, s), 2.20 (3H, s), 2.62 ( 2H, t), 3.97 (2H, s), 5.23 (2H, s), 7.12-7.28 (9H, m), 7.36 (1H, d), 7.44 (m, 1H), 7.53 (m, 1H), 7.67 (1H, d)

실시예 A-27: 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸-d2)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-27: 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl-d2) -4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl-6-oxopyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.40 (2H, m), 1.70 (2H, m), 2.30 (3H, s), 2.69 (2H, t), 3.99 (2H, s), 5.26 (2H, s), 6.94-7.79 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.40 (2H, m), 1.70 (2H, m), 2.30 (3H, s), 2.69 (2H, t), 3.99 ( 2H, s), 5.26 (2H, s), 6.94-7.79 (12H, m)

실시예 A-28: 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸-d2)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-28: 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl- Preparation of 2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.32 (9H, s), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.64 (2H, m), 5.25 (2H, s), 7.14-7.72 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.32 (9H, s), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.64 ( 2H, m), 5.25 (2H, s), 7.14-7.72 (8H, m)

실시예 A-29: 3-(4'-((2-부틸-4-메틸-5-((3-(4-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-29: 3-(4'-((2-butyl-4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl )-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.30-1.68 (4H, m), 2.28 (6H, s), 2.63 (2H, t), 3.96 (2H, s), 4.03 (2H, s), 5.22 (2H, s), 7.08-7.61 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.30-1.68 (4H, m), 2.28 (6H, s), 2.63 (2H, t), 3.96 (2H, s), 4.03 (2H, s), 5.22 (2H, s), 7.08-7.61 (12H, m)

실시예 A-30: 3-(4'-((2-부틸-5-((3-(4-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-30: 3-(4'-((2-butyl-5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.32-1.70 (4H, m), 2.27 (3H, s), 2.65 (2H, t), 3.73 (3H, s), 3.95 (2H, s), 4.01 (2H, s), 5.23 (2H, s), 6.78-7.71 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.32-1.70 (4H, m), 2.27 (3H, s), 2.65 (2H, t), 3.73 (3H, s), 3.95 (2H, s), 4.01 (2H, s), 5.23 (2H, s), 6.78-7.71 (12H, m)

실시예 A-31: 3-(4'-((2-부틸-5-((3-(4-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-31: 3-(4'-((2-butyl-5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.32-1.70 (4H, m), 2.27 (3H, s), 2.65 (2H, t), 3.97 (2H, s), 4.01 (2H, s), 5.23 (2H, s), 7.13-7.72 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.32-1.70 (4H, m), 2.27 (3H, s), 2.65 (2H, t), 3.97 (2H, s), 4.01 (2H, s), 5.23 (2H, s), 7.13-7.72 (12H, m)

실시예 A-32: 3-(4'-((2-부틸-5-((3-(3-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-32: 3-(4'-((2-butyl-5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.31-1.70 (4H, m), 2.27 (3H, s), 2.65 (2H, t), 4.00 (2H, s), 4.01 (2H, s), 5.23 (2H, s), 6.88-7.71 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.31-1.70 (4H, m), 2.27 (3H, s), 2.65 (2H, t), 4.00 (2H, s), 4.01 (2H, s), 5.23 (2H, s), 6.88-7.71 (12H, m)

실시예 A-33: 3-(4'-((2-부틸-5-((3-(3,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-33: 3-(4'-((2-butyl-5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl )-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.87 (3H, t), 1.29-1.68 (4H, m), 2.26 (3H, s), 2.63 (2H, t), 3.98 (2H, s), 4.01 (2H, s), 5.22 (2H, s), 6.62-7.68 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H, t), 1.29-1.68 (4H, m), 2.26 (3H, s), 2.63 (2H, t), 3.98 (2H, s), 4.01 (2H, s), 5.22 (2H, s), 6.62-7.68 (11H, m)

실시예 A-34: 3-(4'-((5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-34: 3-(4'-((5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-( (3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)- Preparation of 1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.99 (3H, t), 1.33 (9H, s), 1.71-1.80 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 4.08 (2H, s), 5.29 (2H, s), 7.19-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.99 (3H, t), 1.33 (9H, s), 1.71-1.80 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 4.08 (2H, s), 5.29 (2H, s), 7.19-7.80 (8H, m)

실시예 A-35: 3-(4'-((5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-35: 3-(4'-((5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97 (3H, t), 1.68-1.78 (2H, m), 2.28 (3H, s), 2.65 (2H, t), 3.99 (2H, s), 4.04 (2H, s), 5.25 (2H, s), 6.94-7.75 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97 (3H, t), 1.68-1.78 (2H, m), 2.28 (3H, s), 2.65 (2H, t), 3.99 (2H, s), 4.04 (2H, s), 5.25 (2H, s), 6.94-7.75 (12H, m)

실시예 A-36: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(피페리딘-1-일메틸)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-36: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxa) Diazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-(4 '-((2-butyl-4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 1.01 (3H, t), 1.49-2.72 (15H, m), 3.56-3.61 (4H, m), 4.13-4.20 (2H, m), 5.28 (2H, s), 7.20-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.01 (3H, t), 1.49-2.72 (15H, m), 3.56-3.61 (4H, m), 4.13-4.20 (2H, m), 5.28 (2H , s), 7.20-7.80 (8H, m)

실시예 A-37: 3-(4'-((4-메틸-5-((3-(4-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-37: 3-(4'-((4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl- Preparation of 2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.98 (3H, t), 1.69-1.78 (2H, m), 2.27-2.29 (6H, d), 2.65 (2H, t), 3.98 (2H, s), 4.04 (2H, s), 5.25 (2H, s), 7.08-7.76 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.98 (3H, t), 1.69-1.78 (2H, m), 2.27-2.29 (6H, d), 2.65 (2H, t), 3.98 (2H, s) ), 4.04 (2H, s), 5.25 (2H, s), 7.08-7.76 (12H, m)

실시예 A-38: 3-(4'-((5-((3-(4-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-38: 3-(4'-((5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.95 (3H, t), 1.65-1.75 (2H, m), 2.26 (3H, s), 2.62 (2H, t), 3.73 (3H, s), 3.94 (2H, s), 4.00 (2H, s), 5.22 (2H, s), 6.78-7.69 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.95 (3H, t), 1.65-1.75 (2H, m), 2.26 (3H, s), 2.62 (2H, t), 3.73 (3H, s), 3.94 (2H, s), 4.00 (2H, s), 5.22 (2H, s), 6.78-7.69 (12H, m)

실시예 A-39: 3-(4'-((5-((3-(4-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-39: 3-(4'-((5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl- Preparation of 2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.98 (3H, t), 1.70-1.79 (2H, m), 2.30 (3H, s), 2.66 (2H, t), 3.99 (2H, s), 4.07 (2H, s), 5.26 (2H, s), 7.18-7.79 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.98 (3H, t), 1.70-1.79 (2H, m), 2.30 (3H, s), 2.66 (2H, t), 3.99 (2H, s), 4.07 (2H, s), 5.26 (2H, s), 7.18-7.79 (12H, m)

실시예 A-40: 3-(4'-((5-((3-(3-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-40: 3-(4'-((5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.95 (3H, t), 1.66-1.76 (2H, m), 2.27 (3H, s), 2.63 (2H, t), 4.01 (2H, s), 4.02 (2H, s), 5.23 (2H, s), 6.88-7.71 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.95 (3H, t), 1.66-1.76 (2H, m), 2.27 (3H, s), 2.63 (2H, t), 4.01 (2H, s), 4.02 (2H, s), 5.23 (2H, s), 6.88-7.71 (12H, m)

실시예 A-41: 3-(4'-((5-((3-(3,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-41: 3-(4'-((5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.67-1.77 (2H, m), 2.29 (3H, s), 2.64 (2H, t), 3.99 (2H, s), 4.04 (2H, s), 5.20 (2H, s), 6.63-7.74 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.67-1.77 (2H, m), 2.29 (3H, s), 2.64 (2H, t), 3.99 (2H, s), 4.04 (2H, s), 5.20 (2H, s), 6.63-7.74 (11H, m)

실시예 A-42: 3-(4'-((5-((3-(2,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-42: 3-(4'-((5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97 (3H, t), 1.69-1.78 (2H, m), 2.29 (3H, s), 2.66 (2H, t), 4.02 (2H, s), 4.06 (2H, s), 5.26 (2H, s), 6.76-7.76 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97 (3H, t), 1.69-1.78 (2H, m), 2.29 (3H, s), 2.66 (2H, t), 4.02 (2H, s), 4.06 (2H, s), 5.26 (2H, s), 6.76-7.76 (11H, m)

실시예 A-43: 3-(4'-((5-((3-사이클로펜틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-43: 3-(4'-((5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-(( 3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2 Preparation of ,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97 (3H, t), 1.62-2.04 (10H, m), 2.29 (3H, s), 2.66 (2H, t), 3.10-3.18 (1H, m), 4.04 (2H, s), 5.26 (2H, s), 7.16-7.76 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97 (3H, t), 1.62-2.04 (10H, m), 2.29 (3H, s), 2.66 (2H, t), 3.10-3.18 (1H, m ), 4.04 (2H, s), 5.26 (2H, s), 7.16-7.76 (8H, m)

실시예 A-44: 3-(4'-((5-((3-(사이클로펜틸메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-44: 3-(4'-((5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo -2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5 -((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl )-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97 (3H, t), 1.16-1.25 (2H, m), 1.46-1.79 (8H, m), 2.21-2.29 (4H, m), 2.63-2.67 (4H, m), 4.05 (2H, s), 5.26 (2H, s), 7.17-7.76 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97 (3H, t), 1.16-1.25 (2H, m), 1.46-1.79 (8H, m), 2.21-2.29 (4H, m), 2.63-2.67 (4H, m), 4.05 (2H, s), 5.26 (2H, s), 7.17-7.76 (8H, m)

실시예 A-45: 3-(4'-((5-((3-(사이클로헥실메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-45: 3-(4'-((5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo -2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5 -((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl )-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.95-1.01 (5H, m), 1.11-1.26 (3H, m), 1.60-1.79 (8H, m), 2.29 (3H, s), 2.54 (2H, d), 2.64 (2H, t), 4.05 (2H, s), 5.26 (2H, s), 7.16-7.76 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.95-1.01 (5H, m), 1.11-1.26 (3H, m), 1.60-1.79 (8H, m), 2.29 (3H, s), 2.54 (2H , d), 2.64 (2H, t), 4.05 (2H, s), 5.26 (2H, s), 7.16-7.76 (8H, m)

실시예 A-46: 3-(4'-((2-부틸-5-((3-(2,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-46: 3-(4'-((2-butyl-5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl )-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.38 (2H, m), 1.68 (2H, m), 2.29 (3H, s), 2.68 (2H, m), 4.02 (2H, s), 4.06 (2H, s), 5.26 (2H, s), 6.78-6.81 (2H, m), 7.17-7.77 (9H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.38 (2H, m), 1.68 (2H, m), 2.29 (3H, s), 2.68 (2H, m), 4.02 ( 2H, s), 4.06 (2H, s), 5.26 (2H, s), 6.78-6.81 (2H, m), 7.17-7.77 (9H, m)

실시예 A-47: 3-(4'-((2-부틸-5-((3-(사이클로헥실메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-yl)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-47: 3-(4'-((2-butyl-5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2- Preparation of yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.38 (2H, m), 1.68 (2H, m), 2.30 (3H, s), 2.55 (2H, d), 2.68 (2H, m), 4.07 (2H, s), 5.27 (2H, s), 7.18-7.79 (8H,m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.38 (2H, m), 1.68 (2H, m), 2.30 (3H, s), 2.55 (2H, d), 2.68 ( 2H, m), 4.07 (2H, s), 5.27 (2H, s), 7.18-7.79 (8H,m)

실시예 A-48: 3-(4'-((2-부틸-5-((3-(사이클로펜틸메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-48: 3-(4'-((2-butyl-5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2- Preparation of yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.21 (2H, m), 1.41 (2H, m), 1.45-1.80 (8H, m), 2.26 (1H, m), 2.30 (3H, s), 2.66 (2H, d), 2.68 (2H, s), 4.06 (2H, s), 5.27 (2H, s), 7.18-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.21 (2H, m), 1.41 (2H, m), 1.45-1.80 (8H, m), 2.26 (1H, m), 2.30 (3H, s), 2.66 (2H, d), 2.68 (2H, s), 4.06 (2H, s), 5.27 (2H, s), 7.18-7.78 (8H, m)

실시예 A-49:Example A-49: 3-(4'-((2-부틸-5-((3-사이클로펜틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 3-(4'-((2-butyl-5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine-1 (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl-5-((3 -cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol- Preparation of 5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.39 (2H, m), 1.60-2.07 (10H, m), 2.30 (3H, s), 2.68 (2H, t), 3.15 (1H, m), 4.05 (2H, s), 5.27 (2H, s), 7.17-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.39 (2H, m), 1.60-2.07 (10H, m), 2.30 (3H, s), 2.68 (2H, t), 3.15 (1H, m), 4.05 (2H, s), 5.27 (2H, s), 7.17-7.78 (8H, m)

실시예 A-50: 3-(4'-((5-((3-(사이클로프로필메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-50: 3-(4'-((5-((3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo -2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5 -((3-(cyclopropylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl )-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.20-0.24 (2H, m), 0.50-0.55 (2H, m), 0.98 (3H, t), 1.05-1.13 (1H, m), 1.70-1.79 (2H, m), 2.32 (3H, s), 2.58 (2H, d), 2.66 (2H, t), 4.06 (2H, s), 5.26 (2H, s), 7.17-7.77 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.20-0.24 (2H, m), 0.50-0.55 (2H, m), 0.98 (3H, t), 1.05-1.13 (1H, m), 1.70-1.79 (2H, m), 2.32 (3H, s), 2.58 (2H, d), 2.66 (2H, t), 4.06 (2H, s), 5.26 (2H, s), 7.17-7.77 (8H, m)

실시예 A-51: 3-(4'-((5-((3-(2-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-51: 3-(4'-((5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl- Preparation of 2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 1.00 (3H, t), 1.71-1.81 (2H, m), 2.31 (3H, s), 2.68 (2H, t), 4.11 (2H, s), 4.17 (2H, s), 5.28 (2H, s), 7.17-7.82 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.00 (3H, t), 1.71-1.81 (2H, m), 2.31 (3H, s), 2.68 (2H, t), 4.11 (2H, s), 4.17 (2H, s), 5.28 (2H, s), 7.17-7.82 (12H, m)

실시예 A-52: 3-(4'-((5-((3-(3,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-52: 3-(4'-((5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.68-1.77 (2H, m), 2.29 (3H, s), 2.65 (2H, t), 3.97 (2H, s), 4.04 (2H, s), 5.24 (2H, s), 6.98-7.74 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.68-1.77 (2H, m), 2.29 (3H, s), 2.65 (2H, t), 3.97 (2H, s), 4.04 (2H, s), 5.24 (2H, s), 6.98-7.74 (11H, m)

실시예 A-53: 3-(4'-((5-((3-(2,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-53: 3-(4'-((5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97 (3H, t), 1.69-1.78 (2H, m), 2.30 (3H, s), 2.66 (2H, t), 4.03 (2H, s), 4.06 (2H, s), 5.25 (2H, s), 6.86-7.76 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97 (3H, t), 1.69-1.78 (2H, m), 2.30 (3H, s), 2.66 (2H, t), 4.03 (2H, s), 4.06 (2H, s), 5.25 (2H, s), 6.86-7.76 (11H, m)

실시예 A-54: 3-(4'-((5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-54: 3-(4'-((5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 1.00 (3H, t), 1.75 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 4.07 (2H, s), 4.09 (2H, s), 5.27 (2H, s), 7.05 (2H, m), 7.28 (4H, m), 7.30 (2H, m), 7.39 (1H, d), 7.49 (1H, m), 7.61 (1H, m), 7.80 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.00 (3H, t), 1.75 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 4.07 (2H, s), 4.09 ( 2H, s), 5.27 (2H, s), 7.05 (2H, m), 7.28 (4H, m), 7.30 (2H, m), 7.39 (1H, d), 7.49 (1H, m), 7.61 (1H , m), 7.80 (1H, d)

실시예 A-55: 3-(4'-((5-((3-(4-브로모벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-55: 3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.99 (3H, t), 1.71-1.80 (2H, m), 2.30 (3H, s), 2.67 (2H, t), 3.97 (2H, s), 4.08 (2H, s), 5.27 (2H, s), 7.15-7.80 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.99 (3H, t), 1.71-1.80 (2H, m), 2.30 (3H, s), 2.67 (2H, t), 3.97 (2H, s), 4.08 (2H, s), 5.27 (2H, s), 7.15-7.80 (12H, m)

실시예 A-56: 3-(4'-((5-((3-(3-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-56: 3-(4'-((5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl- Preparation of 2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.95 (3H, t), 1.66-1.75 (2H, m), 2.27 (3H, s), 2.63 (2H, t), 3.98 (2H, s), 4.02 (2H, s), 5.22 (2H, s), 7.11-7.70 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.95 (3H, t), 1.66-1.75 (2H, m), 2.27 (3H, s), 2.63 (2H, t), 3.98 (2H, s), 4.02 (2H, s), 5.22 (2H, s), 7.11-7.70 (12H, m)

실시예 A-57: 3-(4'-((5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2,6-dichlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-57: 3-(4'-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((5-((3-(2,6-dichlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.95 (3H, t), 1.66-1.76 (2H, m), 2.27 (3H, s), 2.63 (2H, t), 4.01 (2H, s), 4.36 (2H, s), 5.23 (2H, s), 7.13-7.71 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.95 (3H, t), 1.66-1.76 (2H, m), 2.27 (3H, s), 2.63 (2H, t), 4.01 (2H, s), 4.36 (2H, s), 5.23 (2H, s), 7.13-7.71 (11H, m)

실시예 A-58: 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(2,4,6-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-58: 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2,4,6-trifluorobenzyl)-1,2,4 -Oxadiazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((4-methyl-6-oxo-2-propyl-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin- Preparation of 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.94 (3H, t), 1.65-1.75 (2H, m), 2.26 (3H, s), 2.62 (2H, t), 4.00 (2H, s), 4.01 (2H, s), 5.22 (2H, s), 6.63-7.70 (10H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.94 (3H, t), 1.65-1.75 (2H, m), 2.26 (3H, s), 2.62 (2H, t), 4.00 (2H, s), 4.01 (2H, s), 5.22 (2H, s), 6.63-7.70 (10H, m)

실시예 A-59: 3-(4'-((4-메틸-6-옥소-5-((3-(피페리딘-1-일)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-yl)-1,2,4-oxadiazol-5-yl)methyl)-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-59: 3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-yl)-1,2,4-oxadiazole-5- 1)methyl)-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((4-methyl-6-oxo-5-((3-(piperidin-1-yl)-1,2,4-oxadiazol-5-yl)methyl)-2-propylpyrimidin-1(6H)-yl )methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

1H-NMR (400 MHz, CDCl3): δ 1.00 (3H, t), 1.58-1.81 (8H, m), 2.33 (3H, s), 2.68 (2H, t), 3.33-3.36 (4H, m), 3.96 (2H, s), 5.28 (2H, s), 7.20-7.82 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.00 (3H, t), 1.58-1.81 (8H, m), 2.33 (3H, s), 2.68 (2H, t), 3.33-3.36 (4H, m ), 3.96 (2H, s), 5.28 (2H, s), 7.20-7.82 (8H, m)

실시예 A-60: 3-(4'-((5-((3-사이클로헥실-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-60: 3-(4'-((5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-(( 3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2 Preparation of ,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.99 (3H, t), 1.22-1.99 (12H, m), 2.32 (3H, s), 2.66-2.76 (3H, m), 4.08 (2H, s), 5.28 (2H, s), 7.19-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.99 (3H, t), 1.22-1.99 (12H, m), 2.32 (3H, s), 2.66-2.76 (3H, m), 4.08 (2H, s) ), 5.28 (2H, s), 7.19-7.80 (8H, m)

실시예 A-61: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-61: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4- Oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-( 4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.03 (2H, s), 4.22 (2H, s), 5.23 (2H, s), 7.13-7.70 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.03 ( 2H, s), 4.22 (2H, s), 5.23 (2H, s), 7.13-7.70 (12H, m)

실시예 A-62: 3-(4'-((2-부틸-4-메틸-5-((3-(2-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-62: 3-(4'-((2-butyl-4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl )-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.36 (2H, m), 1.64 (2H, m), 2.25 (3H, s), 2.28 (3H, s), 2.64 (2H, t), 3.97 (2H, s), 3.99 (2H, s), 5.22 (2H, s), 7.03-7.68 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.36 (2H, m), 1.64 (2H, m), 2.25 (3H, s), 2.28 (3H, s), 2.64 ( 2H, t), 3.97 (2H, s), 3.99 (2H, s), 5.22 (2H, s), 7.03-7.68 (12H, m)

실시예 A-63: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(3-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-63: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4- Oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-( 4'-((2-butyl-4-methyl-6-oxo-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.02 (2H, s), 4.07 (2H, s), 5.23 (2H, s), 7.13-7.70 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.02 ( 2H, s), 4.07 (2H, s), 5.23 (2H, s), 7.13-7.70 (12H, m)

실시예 A-64: 3-(4'-((2-부틸-5-((3-(2,3-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-64: 3-(4'-((2-butyl-5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl )-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.36 (2H, m), 1.65 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.02 (2H, s), 4.08 (2H, s), 5.23 (2H, s), 6.99-7.71 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.36 (2H, m), 1.65 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.02 ( 2H, s), 4.08 (2H, s), 5.23 (2H, s), 6.99-7.71 (11H, m)

실시예 A-65: 3-(4'-((4-메틸-6-옥소-5-((3-(피페리딘-1-일메틸)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-65: 3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazole-5 -Yl)methyl)-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 1.01 (3H, t), 1.49-2.72 (15H, m), 3.56-3.61 (2H, m), 4.13-4.20 (5H, m), 5.28 (2H, s), 7.20-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.01 (3H, t), 1.49-2.72 (15H, m), 3.56-3.61 (2H, m), 4.13-4.20 (5H, m), 5.28 (2H , s), 7.20-7.80 (8H, m)

실시예 A-66: 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(3-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-66: 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4- Oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-( 4'-((4-methyl-6-oxo-2-propyl-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.68-1.78 (2H, m), 2.28 (3H, s), 2.65 (2H, t), 4.04 (2H, s), 4.08 (2H, s), 5.24 (2H, s), 7.14-7.74 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.68-1.78 (2H, m), 2.28 (3H, s), 2.65 (2H, t), 4.04 (2H, s), 4.08 (2H, s), 5.24 (2H, s), 7.14-7.74 (12H, m)

실시예 A-67: 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(4-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-67: 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4- Oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-( 4'-((4-methyl-6-oxo-2-propyl-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.68-1.77 (2H, m), 2.29 (3H, s), 2.64 (2H, t, J=7.8Hz), 4.04 (2H, s), 4.07 (2H, s), 5.24 (2H, s), 7.14-7.73 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.68-1.77 (2H, m), 2.29 (3H, s), 2.64 (2H, t, J=7.8Hz), 4.04 ( 2H, s), 4.07 (2H, s), 5.24 (2H, s), 7.14-7.73 (12H, m)

실시예 A-68: 3-(4'-((5-((3-(1-(4-플루오로페닐)사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-68: 3-(4'-((5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl) -4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3 -(4'-((5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin Preparation of -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 1.00 (3H, t), 1.55-1.58 (4H, m), 1.72-1.81 (2H, m), 2.31 (3H, s), 2.69 (2H, t), 4.05 (2H, s), 5.28 (2H, s), 6.93-7.82 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.00 (3H, t), 1.55-1.58 (4H, m), 1.72-1.81 (2H, m), 2.31 (3H, s), 2.69 (2H, t ), 4.05 (2H, s), 5.28 (2H, s), 6.93-7.82 (12H, m)

실시예 A-69: 3-(4'-((4-메틸-5-((3-(몰폴리노메틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-69: 3-(4'-((4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2- Preparation of yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.95 (3H, t), 1.67-1.77 (2H, m), 2.38 (3H, s), 2.46-2.64 (6H, m), 3.55-3.59 (6H, m), 4.09 (2H, s), 5.18 (2H, s), 6.88-7.62 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.95 (3H, t), 1.67-1.77 (2H, m), 2.38 (3H, s), 2.46-2.64 (6H, m), 3.55-3.59 (6H , m), 4.09 (2H, s), 5.18 (2H, s), 6.88-7.62 (8H, m)

실시예 A-70: 3-(4'-((4-메틸-6-옥소-5-((3-(1-페닐사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-70: 3-(4'-((4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl) Methyl)-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.71-1.76 (2H, m), 1.86-1.94 (1H, m), 2.02-2.14 (1H, m), 2.30 (3H, s), 2.61-2.68 (4H, m), 2.79-2.86 (2H, m), 4.04 (2H, s), 5.23 (2H, s), 7.00-7.71 (13H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.71-1.76 (2H, m), 1.86-1.94 (1H, m), 2.02-2.14 (1H, m), 2.30 (3H , s), 2.61-2.68 (4H, m), 2.79-2.86 (2H, m), 4.04 (2H, s), 5.23 (2H, s), 7.00-7.71 (13H, m)

실시예 A-71: 3-(4'-((2-부틸-5-((3-(2,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-71: 3-(4'-((2-butyl-5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl )-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.35-1.74 (4H, m), 2.31 (3H, s), 2.69 (2H, t), 4.05 (2H, s), 4.10 (2H, s), 5.27 (2H, s), 6.86-7.80 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.35-1.74 (4H, m), 2.31 (3H, s), 2.69 (2H, t), 4.05 (2H, s), 4.10 (2H, s), 5.27 (2H, s), 6.86-7.80 (11H, m)

실시예 A-72: 3-(4'-((2-부틸-5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-72: 3-(4'-((2-butyl-5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl )-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.34-1.73 (4H, m), 2.29 (3H, s), 2.68 (2H, t), 4.05 (2H, s), 4.08 (2H, s), 5.26 (2H, s), 6.84-7.77 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.34-1.73 (4H, m), 2.29 (3H, s), 2.68 (2H, t), 4.05 (2H, s), 4.08 (2H, s), 5.26 (2H, s), 6.84-7.77 (11H, m)

실시예 A-73: 3-(4'-((2-부틸-5-((3-(2-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-73: 3-(4'-((2-butyl-5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.34-1.73 (4H, m), 2.30 (3H, s), 2.69 (2H, t), 4.08 (2H, s), 4.17 (2H, s), 5.27 (2H, s), 7.17-7.78 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.34-1.73 (4H, m), 2.30 (3H, s), 2.69 (2H, t), 4.08 (2H, s), 4.17 (2H, s), 5.27 (2H, s), 7.17-7.78 (12H, m)

실시예 A-74: 3-(4'-((2-부틸-5-((3-(2,6-다이클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2,6-dichlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-74: 3-(4'-((2-butyl-5-((3-(2,6-dichlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl) -4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((2-butyl-5-((3-(2,6-dichlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.33-1.71 (4H, m), 2.28 (3H, s), 2.67 (2H, t), 4.03 (2H, s), 4.37 (2H, s), 5.25 (2H, s), 7.13-7.74 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.33-1.71 (4H, m), 2.28 (3H, s), 2.67 (2H, t), 4.03 (2H, s), 4.37 (2H, s), 5.25 (2H, s), 7.13-7.74 (11H, m)

실시예 A-75: 3-(4'-((4-메틸-5-((3-(2-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-75: 3-(4'-((4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl- Preparation of 2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.87 (3H. t), 1.63 (2H, m), 2.21 (3H, s), 2.29 (3H, s), 2.49 (2H, t), 3.85 (2H, s), 3.98 (2H, s), 5.07 (2H, s), 6.82 (2H, d), 6.95 (3H, t), 7.07 (3H, m), 7.19 (2H, m), 7.34 (1H, m), 7.55 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H. t), 1.63 (2H, m), 2.21 (3H, s), 2.29 (3H, s), 2.49 (2H, t), 3.85 ( 2H, s), 3.98 (2H, s), 5.07 (2H, s), 6.82 (2H, d), 6.95 (3H, t), 7.07 (3H, m), 7.19 (2H, m), 7.34 (1H) , m), 7.55 (1H, d)

실시예 A-76: 3-(4'-((5-((3-(2,3-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-76: 3-(4'-((5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.98 (3H, t), 1.75 (2H, m), 2.30 (3H, s), 2.66 (2H, t), 4.07 (2H, s), 4.10 (2H, s), 5.26 (2H, s), 7.02 (3H, m), 7.18 (2H, m), 7.28 (2H, t), 7.38 (1H, t), 7.46 (1H, m), 7.46 (1H, m), 7.58 (1H, m), 7.60 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.98 (3H, t), 1.75 (2H, m), 2.30 (3H, s), 2.66 (2H, t), 4.07 (2H, s), 4.10 ( 2H, s), 5.26 (2H, s), 7.02 (3H, m), 7.18 (2H, m), 7.28 (2H, t), 7.38 (1H, t), 7.46 (1H, m), 7.46 (1H) , m), 7.58 (1H, m), 7.60 (1H, d)

실시예 A-77: 3-(4'-((5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-77: 3-(4'-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)- Preparation of yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97 (3H, t), 1.73 (2H, m), 2.27 (3H, s), 2.64 (2H, m), 4.02 (2H, s), 4.08 (2H, s), 5.23 (2H, s), 6.88 (2H, t), 7.12 (2H, m), 7.20 (1H, m), 7.24 (2H, m), 7.29 (2H, m), 7.54 (1H, m), 7.59(1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97 (3H, t), 1.73 (2H, m), 2.27 (3H, s), 2.64 (2H, m), 4.02 (2H, s), 4.08 ( 2H, s), 5.23 (2H, s), 6.88 (2H, t), 7.12 (2H, m), 7.20 (1H, m), 7.24 (2H, m), 7.29 (2H, m), 7.54 (1H) , m), 7.59 (1H, d)

실시예 A-78: 3-(4'-((5-((3-(3-클로로-5-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-78: 3-(4'-((5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.72 (2H, m), 2.30 (3H, s), 2.65 (2H, t), 3.99 (2H, s), 4.05 (2H, s), 5.25 (2H, s), 6.94 (2H, m), 7.08 (1H, s), 7.14 (2H, d), 7.27 (2H, m), 7.38 (1H, d), 7.46 (1H, t), 7.64 (1H, m), 7.72 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.72 (2H, m), 2.30 (3H, s), 2.65 (2H, t), 3.99 (2H, s), 4.05 ( 2H, s), 5.25 (2H, s), 6.94 (2H, m), 7.08 (1H, s), 7.14 (2H, d), 7.27 (2H, m), 7.38 (1H, d), 7.46 (1H) , t), 7.64 (1H, m), 7.72 (1H, d)

실시예 A-79: 3-(4'-((5-((3-(4-브로모벤질)-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-79: 3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.31-1.69 (4H, m), 2.29 (3H, s), 2.64 (2H, t), 3.94 (2H, s), 4.03 (2H, s), 5.22 (2H, s), 7.07-7.66 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.31-1.69 (4H, m), 2.29 (3H, s), 2.64 (2H, t), 3.94 (2H, s), 4.03 (2H, s), 5.22 (2H, s), 7.07-7.66 (12H, m)

실시예 A-80: 3-(4'-((2-부틸-5-((3-(3-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-80: 3-(4'-((2-butyl-5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.31-1.69 (4H, m), 2.28 (3H, s), 2.65 (2H, t), 3.98 (2H, s), 4.02 (2H, s), 5.22 (2H, s), 7.10-7.69 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.31-1.69 (4H, m), 2.28 (3H, s), 2.65 (2H, t), 3.98 (2H, s), 4.02 (2H, s), 5.22 (2H, s), 7.10-7.69 (12H, m)

실시예 A-81: 3-(4'-((2-부틸-5-((3-(3,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-81: 3-(4'-((2-butyl-5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl )-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.88 (3H, t), 1.31-1.70 (4H, m), 2.28 (3H, s), 2.65 (2H, t), 3.96 (2H, s), 4.02 (2H, s), 5.23 (2H, s), 7.00-7.70 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.31-1.70 (4H, m), 2.28 (3H, s), 2.65 (2H, t), 3.96 (2H, s), 4.02 (2H, s), 5.23 (2H, s), 7.00-7.70 (11H, m)

실시예 A-82: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(4-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-82: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4- Oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-( 4'-((2-butyl-4-methyl-6-oxo-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.28 (3H, s), 2.65 (2H, t), 4.03 (2H, s), 4.07 (2H, s), 5.24 (2H, s), 7.14-7.72 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.28 (3H, s), 2.65 (2H, t), 4.03 ( 2H, s), 4.07 (2H, s), 5.24 (2H, s), 7.14-7.72 (12H, m)

실시예 A-83: 3-(4'-((2-부틸-5-((3-(1-(4-플루오로페닐)사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-83: 3-(4'-((2-butyl-5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole-5- 1)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one { 3-(4'-((2-butyl-5-((3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Preparation of oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.29 (2H, m), 1.36 (2H, m), 1.54 (2H, m), 1.66 (2H, m), 2.28 (3H, s), 2.66 (2H, t), 3.98 (2H, s), 5.24 (2H, s), 6.95-7.73 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.29 (2H, m), 1.36 (2H, m), 1.54 (2H, m), 1.66 (2H, m), 2.28 ( 3H, s), 2.66 (2H, t), 3.98 (2H, s), 5.24 (2H, s), 6.95-7.73 (12H, m)

실시예 A-84: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(1-페닐사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-84: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 1.87-2.18 (2H, m), 2.62-2.70 (4H, m), 2.86 (2H, m), 3.96 (2H, s), 5.23 (2H, s), 7.12-7.68 (13H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 1.87-2.18 (2H, m), 2.62-2.70 (4H, m ), 2.86 (2H, m), 3.96 (2H, s), 5.23 (2H, s), 7.12-7.68 (13H, m)

실시예 A-85: 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(2-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-85: 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4- Oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-( 4'-((4-methyl-6-oxo-2-propyl-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.73 (2H, m), 2.28 (3H, s), 2.64 (2H, t), 4.05 (2H, s), 4.23 (2H, s), 5.25 (2H, s), 7.15 (2H, m), 7.27 (1H, m), 7.33 (1H, m), 7.38 (3H, m), 7.46 (2H, m), 7.60 (1H, t), 7.71 (1H, d), 7.74 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.73 (2H, m), 2.28 (3H, s), 2.64 (2H, t), 4.05 (2H, s), 4.23 ( 2H, s), 5.25 (2H, s), 7.15 (2H, m), 7.27 (1H, m), 7.33 (1H, m), 7.38 (3H, m), 7.46 (2H, m), 7.60 (1H) , t), 7.71 (1H, d), 7.74 (1H, d)

실시예 A-86: 3-(4'-((5-((3-(1-(3-플루오로페닐)사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(1-(3-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Example A-86: 3-(4'-((5-((3-(1-(3-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl) -4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3 -(4'-((5-((3-(1-(3-fluorophenyl)cyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.97 (3H, t), 1.31-1.33 (2H, m), 1.55-1.57 (2H, m), 1.69-1.78 (2H, m), 2.29 (3H, s), 2.65 (2H, t), 4.01 (2H, s), 5.25 (2H, s), 6.90-7.75 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.97 (3H, t), 1.31-1.33 (2H, m), 1.55-1.57 (2H, m), 1.69-1.78 (2H, m), 2.29 (3H , s), 2.65 (2H, t), 4.01 (2H, s), 5.25 (2H, s), 6.90-7.75 (12H, m)

실시예 A-87: 3-(4'-((5-((3-(2-클로로-4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-87: 3-(4'-((5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.99 (3H, t), 1.71-1.80 (2H, m), 2.31 (3H, s), 2.68 (2H, t), 4.08 (2H, s), 4.12 (2H, s), 5.27 (2H, s), 6.89-7.79 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.99 (3H, t), 1.71-1.80 (2H, m), 2.31 (3H, s), 2.68 (2H, t), 4.08 (2H, s), 4.12 (2H, s), 5.27 (2H, s), 6.89-7.79 (11H, m)

실시예 A-88: 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(3,4,5-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-88: 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3,4,5-trifluorobenzyl)-1,2,4 -Oxadiazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((4-methyl-6-oxo-2-propyl-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin- Preparation of 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.68-1.77 (2H, m), 2.30 (3H, s), 2.65 (2H, t), 3.95 (2H, s), 4.05 (2H, s), 5.24 (22H, s), 6.88-7.74 (10H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.68-1.77 (2H, m), 2.30 (3H, s), 2.65 (2H, t), 3.95 (2H, s), 4.05 (2H, s), 5.24 (22H, s), 6.88-7.74 (10H, m)

실시예 A-89: 3-(4'-((2-부틸-4-메틸-5-((3-(몰폴리노메틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-89: 3-(4'-((2-butyl-4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl )-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2 Preparation of -yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.92 (3H, t), 1.40 (2H, m), 1.70 (2H, m), 2.36 (3H, s), 2.52 (4H, t), 2.69 (2H, t), 3.64 (4H, d), 3.66 (2H, s), 4.17 (2H, s), 5.29 (2H, s), 7.20 (2H, d), 7.31 (2H, d), 7.41 (1H, d), 7.50 (1H, t), 7.60 (1H, t), 7.78 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 1.40 (2H, m), 1.70 (2H, m), 2.36 (3H, s), 2.52 (4H, t), 2.69 ( 2H, t), 3.64 (4H, d), 3.66 (2H, s), 4.17 (2H, s), 5.29 (2H, s), 7.20 (2H, d), 7.31 (2H, d), 7.41 (1H , d), 7.50 (1H, t), 7.60 (1H, t), 7.78 (1H, d)

실시예 A-90: 3-(4'-((2-부틸-4-메틸-5-((3-(3-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(3-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-90: 3-(4'-((2-butyl-4-methyl-5-((3-(3-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl )-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-5-((3-(3-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl Preparation of -2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.40 (2H, m), 2.28 (3H, s), 2.68 (2H, t), 3.99 (2H, s), 4.05 (2H, s), 5.26 (2H, s), 7.10 (3H, m), 7.15 (3H, m), 7.36 (2H, m), 7.38 (1H, m), 7.58 (1H, t), 7.75 (1H, t), 7.77 (1H, t) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.40 (2H, m), 2.28 (3H, s), 2.68 (2H, t), 3.99 (2H, s), 4.05 ( 2H, s), 5.26 (2H, s), 7.10 (3H, m), 7.15 (3H, m), 7.36 (2H, m), 7.38 (1H, m), 7.58 (1H, t), 7.75 (1H) , t), 7.77 (1H, t)

실시예 A-91: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2,4,6-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-91: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2,4,6-trifluorobenzyl)-1,2,4 -Oxadiazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-4-methyl-6-oxo-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin- Preparation of 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.02 (2H, s), 5.24 (2H, s), 6.67 (2H, t), 7.27 (2H, d), 7.38 (2H, d), 7.46 (1H, m), 7.56 (1H, t), 7.68 (1H, m), 7.70 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.36 (2H, m), 1.66 (2H, m), 2.27 (3H, s), 2.65 (2H, t), 4.02 ( 2H, s), 5.24 (2H, s), 6.67 (2H, t), 7.27 (2H, d), 7.38 (2H, d), 7.46 (1H, m), 7.56 (1H, t), 7.68 (1H) , m), 7.70 (1H, d)

실시예 A-92: 3-(4'-((2-부틸-5-((3-사이클로헥실-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-92: 3-(4'-((2-butyl-5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.26 (4H, m), 1.66 (10H, m), 2.04 (1H, m), 2.32 (3H, d), 2.65 (2H, t), 4.13 (2H, s), 5.28 (2H, s), 7.14 (2H, m), 7.28 (2H, d), 7.37 (1H, m), 7.42 (1H, m), 7.51 (1H, m), 7.69 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.26 (4H, m), 1.66 (10H, m), 2.04 (1H, m), 2.32 (3H, d), 2.65 ( 2H, t), 4.13 (2H, s), 5.28 (2H, s), 7.14 (2H, m), 7.28 (2H, d), 7.37 (1H, m), 7.42 (1H, m), 7.51 (1H) , m), 7.69 (1H, d)

실시예 A-93: 3-(4'-((5-((3-(2-클로로-6-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-93: 3-(4'-((5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.95 (3H, t), 1.66-1.75 (2H, m), 2.26 (3H, s), 2.63 (2H, t), 4.01 (2H, s), 4.19 (2H, s), 5.30 (2H, s), 6.96-7.71 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.95 (3H, t), 1.66-1.75 (2H, m), 2.26 (3H, s), 2.63 (2H, t), 4.01 (2H, s), 4.19 (2H, s), 5.30 (2H, s), 6.96-7.71 (11H, m)

실시예 A-94: 3-(4'-((4-메틸-5-((3-(2-메틸펜탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸l)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-94: 3-(4'-((4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyl l)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2-propylpyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.83 (3H, t), 0.96 (3H, t), 1.10-1.20 (2H, m), 1.29 (6H, s), 1.58-1.77 (4H, m), 2.27 (3H, s), 2.64 (2H, t), 4.04 (2H, s), 5.26 (2H, s), 7.15-7.75 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.83 (3H, t), 0.96 (3H, t), 1.10-1.20 (2H, m), 1.29 (6H, s), 1.58-1.77 (4H, m ), 2.27 (3H, s), 2.64 (2H, t), 4.04 (2H, s), 5.26 (2H, s), 7.15-7.75 (8H, m)

실시예 A-95: 3-(4'-((2-부틸-5-((3-(3-클로로-5-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-95: 3-(4'-((2-butyl-5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl) Methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1 Preparation of (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.92 (3H, t), 1.72 (2H, m), 2.33 (3H, s), 2.72 (2H, t), 4.00 (2H, s), 4.09 (2H, s), 5.28 (2H, s), 6.91 (3H, m), 7.07 (1H, d), 7.19 (2H, d), 7.20 (1H, d), 7.38 (1H, d), 7.41 (1H, d), 7.49 (1H, t), 7.60 (1H, t), 7.78 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 1.72 (2H, m), 2.33 (3H, s), 2.72 (2H, t), 4.00 (2H, s), 4.09 ( 2H, s), 5.28 (2H, s), 6.91 (3H, m), 7.07 (1H, d), 7.19 (2H, d), 7.20 (1H, d), 7.38 (1H, d), 7.41 (1H) , d), 7.49 (1H, t), 7.60 (1H, t), 7.78 (1H, d)

실시예 A-96: 3-(4'-((2-부틸-5-((3-사이클로프로필-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-96: 3-(4'-((2-butyl-5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((3-cyclopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.22 (2H, m), 0.53 (2H, m), 0.88 (3H, t), 1.26 (1H, t), 1.35 (2H, m), 1.67 (2H, m), 2.30 (3H, s), 2.57 (2H, d), 2.66 (2H, t), 4.04 (2H, s), 5.25 (2H, s), 7.15 (2H, d), 7.28 (2H, d), 7.40 (1H, d), 7.47 (1H, t), 7.59 (1H, t), 7.71 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.22 (2H, m), 0.53 (2H, m), 0.88 (3H, t), 1.26 (1H, t), 1.35 (2H, m), 1.67 ( 2H, m), 2.30 (3H, s), 2.57 (2H, d), 2.66 (2H, t), 4.04 (2H, s), 5.25 (2H, s), 7.15 (2H, d), 7.28 (2H , d), 7.40 (1H, d), 7.47 (1H, t), 7.59 (1H, t), 7.71 (1H, d)

실시예 A-97: 3-(4'-((2-부틸-5-((3-(2-클로로-6-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-97: 3-(4'-((2-butyl-5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl) Methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1 Preparation of (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.36 (2H, m), 1.69 (2H, m), 2.33 (3H, s), 2.64 (2H, s), 4.09 (2H, s), 4.22 (2H, s), 5.25 (2H, s), 7.00 (3H, m), 7.12 (2H, d), 7.20 (2H, m), 7.26 (2H, m), 7.44 (1H, t), 7.58 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.36 (2H, m), 1.69 (2H, m), 2.33 (3H, s), 2.64 (2H, s), 4.09 ( 2H, s), 4.22 (2H, s), 5.25 (2H, s), 7.00 (3H, m), 7.12 (2H, d), 7.20 (2H, m), 7.26 (2H, m), 7.44 (1H) , t), 7.58 (1H, d)

실시예 A-98: 3-(4'-((2-부틸-5-((3-(2-클로로-4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-98: 3-(4'-((2-butyl-5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl) Methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1 Preparation of (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.39 (2H, m), 1.70 (2H, m), 2.32 (3H, s), 2.68 (2H, t), 4.10 (2H, s), 4.13 (2H, s), 5.28 (2H, s), 6.94 (2H, m), 7.15 (2H, m), 7.28 (3H, m), 7.48 (2H, d), 7.58 (1H, t), 7.78 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.39 (2H, m), 1.70 (2H, m), 2.32 (3H, s), 2.68 (2H, t), 4.10 ( 2H, s), 4.13 (2H, s), 5.28 (2H, s), 6.94 (2H, m), 7.15 (2H, m), 7.28 (3H, m), 7.48 (2H, d), 7.58 (1H) , t), 7.78 (1H, d)

실시예 A-99: 3-(4'-((2-부틸-4-메틸-5-((3-(2-메틸펜탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-99: 3-(4'-((2-butyl-4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazole-5 -Yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((2-butyl-4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1( Preparation of 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (6H, m), 1.26 (1H, t), 1.38 (12H, m), 1.69 (2H, m), 2.29 (3H, s), 2.67 (2H, t), 4.14 (2H, s), 5.29 (2H, s), 7.22 (2H, d), 7.38 (2H, d), 7.40 (1H, d), 7.59 (1H, t), 7.61 (1H, t), 7.81 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (6H, m), 1.26 (1H, t), 1.38 (12H, m), 1.69 (2H, m), 2.29 (3H, s), 2.67 ( 2H, t), 4.14 (2H, s), 5.29 (2H, s), 7.22 (2H, d), 7.38 (2H, d), 7.40 (1H, d), 7.59 (1H, t), 7.61 (1H) , t), 7.81 (1H, d)

실시예 A-100: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(3,4,5-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-100: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3,4,5-trifluorobenzyl)-1,2,4 -Oxadiazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-4-methyl-6-oxo-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin- Preparation of 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.38 (1H, m), 1.66 (2H, m), 2.28 (3H, s), 2.67 (2H, t), 3.96 (2H, s), 4.06 (2H, s), 5.25 (2H, s), 6.92 (2H, m), 7.13 (2H, d), 7.26 (2H, m), 7.45 (1H, d), 7.57 (1H, t), 7.66 (1H, t), 7.68 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.38 (1H, m), 1.66 (2H, m), 2.28 (3H, s), 2.67 (2H, t), 3.96 ( 2H, s), 4.06 (2H, s), 5.25 (2H, s), 6.92 (2H, m), 7.13 (2H, d), 7.26 (2H, m), 7.45 (1H, d), 7.57 (1H , t), 7.66 (1H, t), 7.68 (1H, d)

실시예 A-101: 3-(4'-((5-((3-(1-(2-클로로페닐)에틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(1-(2-chlorophenyl)ethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-101: 3-(4'-((5-((3-(1-(2-chlorophenyl)ethyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-( 4'-((5-((3-(1-(2-chlorophenyl)ethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1 Preparation of (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.96 (3H, t), 1.63 (3H, d), 1.64-1.69 (2H, m), 2.28 (3H, s), 2.64 (2H, t), 4.07 (2H, s), 4.71-4.77 (1H, m), 5.25 (2H, s), 7.12-7.71 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.63 (3H, d), 1.64-1.69 (2H, m), 2.28 (3H, s), 2.64 (2H, t), 4.07 (2H, s), 4.71-4.77 (1H, m), 5.25 (2H, s), 7.12-7.71 (12H, m)

실시예 A-102: 3-(4'-((2-부틸-5-((3-(2-사이클로헥실프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-cyclohexylpropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-102: 3-(4'-((2-butyl-5-((3-(2-cyclohexylpropan-2-yl)-1,2,4-oxadiazol-5-yl) Methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-5-((3-(2-cyclohexylpropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1 Preparation of (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 0.95-1.20 (5H, m), 1.24 (6H, s), 1.33-1.43 (2H, m), 1.48-1.51 (2H, m), 1.60-1.72 (6H, m), 2.27 (3H, s), 2.67 (2H, t), 4.06 (2H, s), 5.27 (2H, s), 7.17-7.77 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 0.95-1.20 (5H, m), 1.24 (6H, s), 1.33-1.43 (2H, m), 1.48-1.51 (2H , m), 1.60-1.72 (6H, m), 2.27 (3H, s), 2.67 (2H, t), 4.06 (2H, s), 5.27 (2H, s), 7.17-7.77 (8H, m)

실시예 A-103: 3-(4'-((2-부틸-5-((3-(2-(4-클로로-2-플루오로페닐)프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-(4-chloro-2-fluorophenyl)propan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-103: 3-(4'-((2-butyl-5-((3-(2-(4-chloro-2-fluorophenyl)propan-2-yl)-1,2,4 -Oxadiazole-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole- 5(4H)-one {3-(4'-((2-butyl-5-((3-(2-(4-chloro-2-fluorophenyl)propan-2-yl)-1,2,4- Preparation of oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.87 (3H, t), 1.29-1.67 (4H, m), 1.75 (6H, s), 2.20 (3H, s), 2.62 (2H, t), 4.01 (2H, s), 5.23 (2H, s), 6.94-7.68 (11H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H, t), 1.29-1.67 (4H, m), 1.75 (6H, s), 2.20 (3H, s), 2.62 (2H, t), 4.01 (2H, s), 5.23 (2H, s), 6.94-7.68 (11H, m)

실시예 A-104: 3-(4'-((2-부틸-5-((3-(2-(2-클로로-6-플루오로페닐)프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-104: 3-(4'-((2-butyl-5-((3-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1,2,4 -Oxadiazole-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole- 5(4H)-one {3-(4'-((2-butyl-5-((3-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1,2,4- Preparation of oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.92 (3H, t), 1.36-1.45 (11H, m), 1.69-1.77 (2H, m), 2.46 (3H, s), 2.77 (2H, t), 5.33 (2H, s), 7.25-7.08 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 1.36-1.45 (11H, m), 1.69-1.77 (2H, m), 2.46 (3H, s), 2.77 (2H, t ), 5.33 (2H, s), 7.25-7.08 (8H, m)

실시예 A-105: 3-(4'-((2-부틸-5-((3-(3-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-105: 3-(4'-((2-butyl-5-((3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.90 (3H, t), 1.37 (2H, m), 1.68 (2H, m), 2.32 (3H, s), 2.65 (2H, t), 3.67 (3H, s), 4.02 (2H, s), 4.08 (2H, s), 5.28 (2H, s), 6.74 (1H, d), 6.87 (1H, s), 7.09 (1H, d), 7.14 (3H, m), 7.17 (1H, d), 7.19 (1H,s), 7.34 (3H, d), 7.49 (2H, t), 7.59 (1H, t), 7.79 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.37 (2H, m), 1.68 (2H, m), 2.32 (3H, s), 2.65 (2H, t), 3.67 ( 3H, s), 4.02 (2H, s), 4.08 (2H, s), 5.28 (2H, s), 6.74 (1H, d), 6.87 (1H, s), 7.09 (1H, d), 7.14 (3H , m), 7.17 (1H, d), 7.19 (1H,s), 7.34 (3H, d), 7.49 (2H, t), 7.59 (1H, t), 7.79 (1H, d)

실시예 A-106: 3-(4'-((2-부틸-5-((3-(2-메톡시페닐)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example A-106: 3-(4'-((2-butyl-5-((3-(2-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(2-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.87 (3H, t), 1.33-1.68 (4H, m), 2.39 (3H, s), 2.65 (2H, t), 3.82 (3H, s), 4.14 (2H, s), 5.19 (2H, s), 6.90-7.83 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H, t), 1.33-1.68 (4H, m), 2.39 (3H, s), 2.65 (2H, t), 3.82 (3H, s), 4.14 (2H, s), 5.19 (2H, s), 6.90-7.83 (12H, m)

실시예 A-107: 3-(4'-((2-부틸-5-((3-(2-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(2-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-107: 3-(4'-((2-butyl-5-((3-(2-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(2-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.87 (3H, t), 1.31-1.72 (4H, m), 2.34 (3H, s), 2.61 (2H, t), 3.70 (3H, s), 3.95 (2H, s), 4.02 (2H, s), 5.16 (2H, s), 6.77-7.65 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H, t), 1.31-1.72 (4H, m), 2.34 (3H, s), 2.61 (2H, t), 3.70 (3H, s), 3.95 (2H, s), 4.02 (2H, s), 5.16 (2H, s), 6.77-7.65 (12H, m)

실시예 A-108: 3-(4'-((2-부틸-4-메틸-5-((3-(나프탈렌-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-108: 3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl) Methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-4-methyl-5-((3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl) Preparation of methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.87 (3H, t), 1.33-1.65 (4H, m), 2.39 (3H, s), 2.61 (2H, t), 4.15 (2H, s), 5.15 (2H, s), 6.97-7.99 (15H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H, t), 1.33-1.65 (4H, m), 2.39 (3H, s), 2.61 (2H, t), 4.15 (2H, s), 5.15 (2H, s), 6.97-7.99 (15H, m)

실시예 A-109: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(테트라하이드로-2H-피란-4-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(tetrahydro-2H-pyran-4-yl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-109: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(tetrahydro-2H-pyran-4-yl)-1,2,4 -Oxadiazole-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3- (4'-((2-butyl-4-methyl-6-oxo-5-((3-(tetrahydro-2H-pyran-4-yl)-1,2,4-oxadiazol-5-yl)methyl) Preparation of pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.35-1.74 (4H, m), 1.80-1.90 (4H, m), 2.33 (3H, s), 2.69 (2H, t), 2.95-3.02 (1H, m), 3.45-3.51 (2H, m), 3.94-3.99 (2H, m), 4.08 (2H, s), 5.28 (2H, s), 7.18-7.76 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.35-1.74 (4H, m), 1.80-1.90 (4H, m), 2.33 (3H, s), 2.69 (2H, t ), 2.95-3.02 (1H, m), 3.45-3.51 (2H, m), 3.94-3.99 (2H, m), 4.08 (2H, s), 5.28 (2H, s), 7.18-7.76 (8H, m) )

실시예 A-110: 3-(4'-((2-부틸-5-((3-(1-에틸사이클로프로필)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-(1-ethylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-110: 3-(4'-((2-butyl-5-((3-(1-ethylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((3-(1-ethylcyclopropyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.80-1.13 (10H, m), 1.34-1.43 (2H, m), 1.65-1.77 (4H, m), 2.30 (3H, s), 2.68 (2H, t), 4.02 (2H, s), 5.26 (2H, s), 7.15-7.77 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.80-1.13 (10H, m), 1.34-1.43 (2H, m), 1.65-1.77 (4H, m), 2.30 (3H, s), 2.68 (2H , t), 4.02 (2H, s), 5.26 (2H, s), 7.15-7.77 (8H, m)

실시예 A-111: 3-(4'-((2-부틸-5-((3-사이클로부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((3-cyclobutyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-111: 3-(4'-((2-butyl-5-((3-cyclobutyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((3-cyclobutyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.32-1.41 (2H, m), 1.63-1.70 (2H, m), 1.90-2.10 (2H, m), 2.28-2.35 (7H, m), 2.65 (2H, t, J=8Hz), 3.53-3.62 (1H, m), 4.03 (2H, s), 5.24 (2H, s), 7.14-7.72 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.32-1.41 (2H, m), 1.63-1.70 (2H, m), 1.90-2.10 (2H, m), 2.28-2.35 (7H, m), 2.65 (2H, t, J=8Hz), 3.53-3.62 (1H, m), 4.03 (2H, s), 5.24 (2H, s), 7.14-7.72 (8H, m)

실시예 A-112: 3-(4'-((5-((3-(바이사이클로[2.2.1]헵탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((3-(bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-112: 3-(4'-((5-((3-(bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)methyl )-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-((3-(bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4- Preparation of methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.13-1.43 (5H, m), 1.45-1.72 (6H, m), 1.90 (1H, m), 2.28 (3H, s), 2.33 (1H, m), 2.45 (0.8H, m), 2.56 (0.2H, m), 2.66 (2H, t), 2.76 (0.8H, m), 3.10 (0.2H, m), 4.00 (1.5H, s), 4.03 (0.5H, s), 5.25 (2H, s), 7.14-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.13-1.43 (5H, m), 1.45-1.72 (6H, m), 1.90 (1H, m), 2.28 (3H, s) ), 2.33 (1H, m), 2.45 (0.8H, m), 2.56 (0.2H, m), 2.66 (2H, t), 2.76 (0.8H, m), 3.10 (0.2H, m), 4.00 ( 1.5H, s), 4.03 (0.5H, s), 5.25 (2H, s), 7.14-7.80 (8H, m)

실시예 A-113: 3-(4'-((2-부틸-4-메틸-5-((3-(1-메틸사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(1-methylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-113: 3-(4'-((2-butyl-4-methyl-5-((3-(1-methylcyclobutyl)-1,2,4-oxadiazol-5-yl) Methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-4-methyl-5-((3-(1-methylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.89 (3H, t), 1.37 (2H, m), 1.52 (3H, s), 1.68 (2H, m), 1.90-2.10 (4H, m), 2.29 (3H, s), 2.50 (2H, m), 2.65 (2H, t), 4.03 (2H, s), 5.25 (2H, s), 7.14-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.37 (2H, m), 1.52 (3H, s), 1.68 (2H, m), 1.90-2.10 (4H, m), 2.29 (3H, s), 2.50 (2H, m), 2.65 (2H, t), 4.03 (2H, s), 5.25 (2H, s), 7.14-7.80 (8H, m)

실시예 A-114: 3-(4'-((2-부틸-4-메틸-5-((3-(나프탈렌-1-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-1-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-114: 3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-1-yl)-1,2,4-oxadiazol-5-yl) Methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-4-methyl-5-((3-(naphthalen-1-yl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl) Preparation of methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.83 (3H, t), 1.28 (2H, m), 1.58 (2H, m), 2.32 (3H, s), 2.56 (2H, t), 4.18 (2H, s), 5.19 (2H, s), 7.04 (2H, d), 7.15 (2H, m), 7.24 (2H, m), 7.48 (1H, t), 7.54 (4H, m), 7.85 (1H, d), 7.91 (1H, d), 8.17 (1H, d), 8.85 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.83 (3H, t), 1.28 (2H, m), 1.58 (2H, m), 2.32 (3H, s), 2.56 (2H, t), 4.18 ( 2H, s), 5.19 (2H, s), 7.04 (2H, d), 7.15 (2H, m), 7.24 (2H, m), 7.48 (1H, t), 7.54 (4H, m), 7.85 (1H) , d), 7.91 (1H, d), 8.17 (1H, d), 8.85 (1H, d)

실시예 A-115: 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(퀴놀린-2-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example A-115: 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(quinolin-2-yl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-6-oxo-5-((3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)pyrimidin-1(6H)-yl) Preparation of methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400 MHz, CDCl3): δ 0.91 (3H, t), 1.40 (2H, m), 1.80 (2H, m), 2.35 (3H, s), 2.69 (2H, t), 4.26 (2H, s), 5.28 (2H, s), 7.20 (2H, d), 7.27 (1H, d), 7.34 (2H, d), 7.46 (1H, t), 7.60 (2H, m), 7.65 (1H, t), 7.78 (1H, d), 7.84 (1H, d), 8.17 (2H, m), 8.29 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.40 (2H, m), 1.80 (2H, m), 2.35 (3H, s), 2.69 (2H, t), 4.26 ( 2H, s), 5.28 (2H, s), 7.20 (2H, d), 7.27 (1H, d), 7.34 (2H, d), 7.46 (1H, t), 7.60 (2H, m), 7.65 (1H) , t), 7.78 (1H, d), 7.84 (1H, d), 8.17 (2H, m), 8.29 (1H, d)

실시예Example B-1: 3-(4'-((2-부틸-5-((5- B-1: 3-(4'-((2-butyl-5-((5- 터트Turt -부틸-1,2,4--Butyl-1,2,4- 옥사다이아졸Oxadiazole -3-일)-3 days) 메틸methyl )-4-)-4- 메틸methyl -6--6- 옥소피리미딘Oxopyrimidine -1(6H)-일)-1(6H)-day) 메틸methyl )) 바이페닐Biphenyl -2-일)-1,2,4--2-day)-1,2,4- 옥사다이아졸Oxadiazole -5(4H)-온 {3-(4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 -5(4H)-one {3-(4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6 Preparation of -oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

[단계 1] 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세트아마이드 {2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetamide}의 제조[Step 1] 2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- 1)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetamide {2-(2-butyl-4-methyl-6-oxo-1-((2'- Preparation of (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetamide}

Figure 112018068967010-pat00043
Figure 112018068967010-pat00043

에틸 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세테이트 (5 g) 에 암모니아수 (6.9 mL, 10 eq)를 첨가한 후, 상온에서 18 시간 동안 교반하였다. 반응 용액에 H2O 20 mL를 첨가하고, 생성된 슬러리를 여과하였다. 여과물을 45 ℃에서 열풍건조하여 표제 화합물 4.4 g (수율: 92%)을 얻었다.Ethyl 2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)bi Ammonia water (6.9 mL, 10 eq) was added to phenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetate (5 g), followed by stirring at room temperature for 18 hours. 20 mL of H 2 O was added to the reaction solution, and the resulting slurry was filtered. The filtrate was dried by hot air at 45°C to obtain 4.4 g (yield: 92%) of the title compound.

[단계 2] 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세토나이트릴 {2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetonitrile}의 제조[Step 2] 2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- 1)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetonitrile {2-(2-butyl-4-methyl-6-oxo-1-((2' Preparation of -(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetonitrile}

Figure 112018068967010-pat00044
Figure 112018068967010-pat00044

단계 1에서 제조된 화합물 (4.42 g)을 아세토나이트릴 25 mL에 녹인 후, POCl3 (1.1 mL, 1.3 당량)를 첨가하였다. 18 시간 동안 환류 교반하고, 생성된 고체를 여과하여 제거하였다. 여액을 농축한 후 클로로포름 50 mL에 용해시키고, 포화 NaHCO3 50ml를 사용하여 세척하였다. 수층을 CHCl3 (25ml)로 1회 추가 추출하였다. 유기층을 모아 1N HCl 20 ml로 세척하고, 무수 MgSO4로 건조 후 여과하였다. 감압농축 후 에틸아세테이트/헥산 = 16ml/24ml 첨가하고 가열하여 용해시켰다. 2 시간 동안 서서히 냉각하여 얻어진 고체 생성물을 여과 후 에틸아세테이트/헥산 = 1/2 (7ml)로 세척하였다. 얻어진 고체를 45 ℃에서 열풍건조하여 표제 화합물 2.78 g (수율: 65 %)을 수득하였다. After dissolving the compound prepared in Step 1 (4.42 g) in 25 mL of acetonitrile, POCl 3 (1.1 mL, 1.3 eq.) was added. The mixture was stirred at reflux for 18 hours, and the resulting solid was removed by filtration. The filtrate was concentrated, dissolved in 50 mL of chloroform, and washed with 50 mL of saturated NaHCO 3 . The aqueous layer was further extracted once with CHCl 3 (25 ml). The combined organic layers were washed with 20 ml of 1N HCl, dried over anhydrous MgSO 4 and filtered. After concentration under reduced pressure, ethyl acetate/hexane = 16ml/24ml was added and heated to dissolve. The solid product obtained by cooling slowly for 2 hours was filtered and washed with ethyl acetate/hexane = 1/2 (7 ml). The obtained solid was hot-air dried at 45° C. to obtain 2.78 g (yield: 65%) of the title compound.

[단계 3] (Z)-2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)-N'-하이드록시아세트이미드아마이드 {(Z)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N'-hydroxyacetimidamide}의 제조[Step 3] (Z)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiadia) Zol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N'-hydroxyacetimidamide {(Z)-2-(2-butyl- 4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6 Preparation of -dihydropyrimidin-5-yl)-N'-hydroxyacetimidamide}

Figure 112018068967010-pat00045
Figure 112018068967010-pat00045

단계 2에서 제조된 화합물 (0.6 g)을 에탄올 (20 ml)에 녹인 후 하이드록실아민 (0.36 ml, 5 eq)을 첨가하였다. 18 시간 동안 환류 교반하고, 반응 혼합물을 감압 농축하였다. 크로마토그래피 (실리카, 10% MeOH/CHCl3 사용)로 정제하여 표제 화합물 0.37 g (수율: 57 %)을 수득하였다. The compound prepared in Step 2 (0.6 g) was dissolved in ethanol (20 ml), and then hydroxylamine (0.36 ml, 5 eq) was added. The mixture was stirred at reflux for 18 hours, and the reaction mixture was concentrated under reduced pressure. Purification by chromatography (silica, using 10% MeOH/CHCl 3 ) afforded 0.37 g (yield: 57%) of the title compound.

[단계 4] (Z)-2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)-N'-(피발로일옥시)아세트이미드아마이드 {(Z)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N'-(pivaloyloxy)acetimidamide}의 제조[Step 4] (Z)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiadia) Zol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N'-(pivaloyloxy)acetimidamide {(Z)-2-( 2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl) Preparation of -1,6-dihydropyrimidin-5-yl)-N'-(pivaloyloxy)acetimidamide}

Figure 112018068967010-pat00046
Figure 112018068967010-pat00046

단계 3에서 제조된 화합물 (0.4 g), HOBt (0.25 g, 1.1 eq), EDCI (0.37 g, 1.15 eq), 터트-부틸 카르복실산 (0.22 g, 1.3 eq)를 메틸렌클로라이드 10 ml에 녹인 후, 트리에틸아민 (0.35 ml, 1.5 eq)을 적가하였다. 상온에서 18 시간 동안 교반 후, H2O 10 ml를 첨가하고 메틸렌클로라이드 10 ml로 추출하였다. 유기층을 Brine 10 ml로 세척 후, 크로마토그래피 (실리카, 10% MeOH/CHCl3 사용)로 정제하여 표제 화합물 0.167 g (수율: 31 %)을 수득하였다 After dissolving the compound (0.4 g), HOBt (0.25 g, 1.1 eq), EDCI (0.37 g, 1.15 eq), and tert-butyl carboxylic acid (0.22 g, 1.3 eq) prepared in step 3 in 10 ml of methylene chloride , Triethylamine (0.35 ml, 1.5 eq) was added dropwise. After stirring at room temperature for 18 hours, 10 ml of H 2 O was added and extracted with 10 ml of methylene chloride. The organic layer was washed with 10 ml of Brine, and purified by chromatography (silica, using 10% MeOH/CHCl 3 ) to obtain 0.167 g (yield: 31%) of the title compound.

[단계 5] 3-(4'-((2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조[Step 5] 3-(4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl- 5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1 Preparation of ,2,4-oxadiazol-5(4H)-one}

Figure 112018068967010-pat00047
Figure 112018068967010-pat00047

단계 4에서 제조된 화합물 (0.167 g)과 K2CO3 (0.107 g, 1.5 eq)를 톨루엔 10 ml에 녹인 후, 3 시간 동안 환류 교반하였다. 반응 혼합물을 감압 농축하고, 크로마토그래피 (실리카, 10% MeOH/CHCl3 사용)로 정제하여 표제 화합물 0.096 g (수율: 61 %)을 수득하였다. After dissolving the compound prepared in Step 4 (0.167 g) and K 2 CO 3 (0.107 g, 1.5 eq) in 10 ml of toluene, the mixture was stirred at reflux for 3 hours. The reaction mixture was concentrated under reduced pressure and purified by chromatography (silica, using 10% MeOH/CHCl 3 ) to give 0.096 g (yield: 61%) of the title compound.

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, t), 1.35-1.44 (11H, m), 1.65-1.73 (2H, m), 2.32 (3H, s), 2.67 (2H, t), 3.93 (2H, s), 5.29 (2H, s), 7.21-8.57 (8H, m) 1 H-NMR (400MHz, CDCl 3 ): δ 0.91 (3H, t), 1.35-1.44 (11H, m), 1.65-1.73 (2H, m), 2.32 (3H, s), 2.67 (2H, t) , 3.93 (2H, s), 5.29 (2H, s), 7.21-8.57 (8H, m)

<실시예 B-2 내지 B-14><Examples B-2 to B-14>

실시예 B-2 내지 B-14의 화합물은 실시예 B-1과 유사한 방법으로 각 실시예에 대응하는 카르복실산 유도체 화합물을 이용하여 합성하였다.The compounds of Examples B-2 to B-14 were synthesized using a carboxylic acid derivative compound corresponding to each example in a similar manner to Example B-1.

실시예 B-2: 3-(4'-((2-부틸-4-메틸-5-((5-(1-메틸사이클로프로필)-1,2,4-옥사다이아졸-3-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((5-(1-methylcyclopropyl)-1,2,4-oxadiazol-3-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example B-2: 3-(4'-((2-butyl-4-methyl-5-((5-(1-methylcyclopropyl)-1,2,4-oxadiazol-3-yl) Methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-4-methyl-5-((5-(1-methylcyclopropyl)-1,2,4-oxadiazol-3-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.90 (3H, t), 0.95-0.98 (2H, m), 1.34-1.43 (4H, m), 1.51 (3H, s), 1.64-1.72 (2H, m), 2.66 (2H, t), 3.90 (2H, s), 5.28 (2H, s), 7.18-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 0.95-0.98 (2H, m), 1.34-1.43 (4H, m), 1.51 (3H, s), 1.64-1.72 (2H, m), 2.66 (2H, t), 3.90 (2H, s), 5.28 (2H, s), 7.18-7.78 (8H, m)

실시예 B-3: 3-(4'-((2-부틸-5-((5-사이클로프로필-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example B-3: 3-(4'-((2-butyl-5-((5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, t), 1.15-1.20 (4H, m), 1.35-1.44 (2H, m), 1.66-1.73 (2H, m), 2.12-2.18 (1H, m), 2.31 (3H, s), 2.68 (2H, t), 3.89 (2H, s), 5.28 (2H, s), 7.21-7.81 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.15-1.20 (4H, m), 1.35-1.44 (2H, m), 1.66-1.73 (2H, m), 2.12-2.18 ( 1H, m), 2.31 (3H, s), 2.68 (2H, t), 3.89 (2H, s), 5.28 (2H, s), 7.21-7.81 (8H, m)

실시예 B-4: 3-(4'-((2-부틸-5-((5-이소프로필-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example B-4: 3-(4'-((2-butyl-5-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((5-isopropyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, t), 1.35-1.74 (8H, m), 1.65-1.72 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 3.11-3.22 (1H, m), 3.92 (2H, s), 5.28 (2H, s), 7.20-7.79 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.35-1.74 (8H, m), 1.65-1.72 (2H, m), 2.31 (3H, s), 2.67 (2H, t) , 3.11-3.22 (1H, m), 3.92 (2H, s), 5.28 (2H, s), 7.20-7.79 (8H, m)

실시예 B-5: 3-(4'-((2-부틸-5-((5-(1-(4-클로로페닐)사이클로프로필)-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(1-(4-chlorophenyl)cyclopropyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example B-5: 3-(4'-((2-butyl-5-((5-(1-(4-chlorophenyl)cyclopropyl)-1,2,4-oxadiazol-3-yl )Methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3 -(4'-((2-butyl-5-((5-(1-(4-chlorophenyl)cyclopropyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin Preparation of -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.89 (3H, t), 1.32-1.76 (8H, m), 2.26 (3H, s), 2.63 (2H, t), 3.82 (2H, s), 5.27 (2H, s), 7.15-7.73 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.32-1.76 (8H, m), 2.26 (3H, s), 2.63 (2H, t), 3.82 (2H, s), 5.27 (2H, s), 7.15-7.73 (12H, m)

실시예 B-6: 3-(4'-((2-부틸-5-((5-사이클로부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-cyclobutyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example B-6: 3-(4'-((2-butyl-5-((5-cyclobutyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((5-cyclobutyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): 0.90 (3H, t), 1.33-1.42 (2H, m), 1.63-1.71 (2H, m), 1.98-2.21 (2H, m), 2.30 (3H, s), 2.38-2.45 (4H, m), 2.65 (2H, t), 3.65-3.66 (1H, m), 3.90 (2H, s), 5.26 (2H, s), 7.18-7.76 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.90 (3H, t), 1.33-1.42 (2H, m), 1.63-1.71 (2H, m), 1.98-2.21 (2H, m), 2.30 (3H, s ), 2.38-2.45 (4H, m), 2.65 (2H, t), 3.65-3.66 (1H, m), 3.90 (2H, s), 5.26 (2H, s), 7.18-7.76 (8H, m)

실시예 B-7: 3-(4'-((2-부틸-5-((5-(2-플루오로페닐)-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example B-7: 3-(4'-((2-butyl-5-((5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): 0.90 (3H, t), 1.33-1.43 (2H, m), 1.64-1.72 (2H, m), 2.34 (3H, s), 2.67 (2H, t), 4.01 (2H, s), 5.28 (2H, s), 7.19-8.08 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.90 (3H, t), 1.33-1.43 (2H, m), 1.64-1.72 (2H, m), 2.34 (3H, s), 2.67 (2H, t), 4.01 (2H, s), 5.28 (2H, s), 7.19-8.08 (12H, m)

실시예 B-8: 3-(4'-((2-부틸-5-((5-(2-플루오로벤질)-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(2-fluorobenzyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example B-8: 3-(4'-((2-butyl-5-((5-(2-fluorobenzyl)-1,2,4-oxadiazol-3-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((2-butyl-5-((5-(2-fluorobenzyl)-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): 0.89 (3H, t), 1.32-1.70 (4H, m), 2.27 (3H, s), 2.64 (2H, t), 3.88 (2H, s), 4.21 (2H, s), 5.24 (2H, s), 7.04-7.72 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.89 (3H, t), 1.32-1.70 (4H, m), 2.27 (3H, s), 2.64 (2H, t), 3.88 (2H, s), 4.21 ( 2H, s), 5.24 (2H, s), 7.04-7.72 (12H, m)

실시예 B-9: 4'-((2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-카르복실산 {4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-carboxylic acid}의 제조Example B-9: 4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopy Rimidine-1(6H)-yl)methyl)biphenyl-2-carboxylic acid {4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3- Preparation of yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-carboxylic acid}

1H-NMR (400MHz, CDCl3): 0.84 (3H, t), 1.27-1.40 (11H, m), 1.55-1.63 (2H, m), 2.33 (3H, s), 2.65 (2H, t), 4.03 (2H, s), 5.34 (2H, s), 7.16-7.93 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.84 (3H, t), 1.27-1.40 (11H, m), 1.55-1.63 (2H, m), 2.33 (3H, s), 2.65 (2H, t), 4.03 (2H, s), 5.34 (2H, s), 7.16-7.93 (8H, m)

실시예 B-10: 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온 (3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one)의 제조Example B-10: 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-tert-butyl-1,2 ,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one (3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl Preparation of )-2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one)

1H-NMR (400MHz, CDCl3): 0.93 (3H, t), 1.38-1.47 (11H, m), 1.70-1.77 (2H, m), 2.35 (3H, s), 2.73 (2H, t), 3.98 (2H, s), 5.28 (2H, s), 7.19-8.13 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.93 (3H, t), 1.38-1.47 (11H, m), 1.70-1.77 (2H, m), 2.35 (3H, s), 2.73 (2H, t), 3.98 (2H, s), 5.28 (2H, s), 7.19-8.13 (8H, m)

실시예 B-11: 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-(2-플루오로페닐)-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온 {3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one}의 제조Example B-11: 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(2-fluorophenyl) -1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidine-4(3H)-one {3-((2'-(1H-tetrazol-5-yl)biphenyl-4 Preparation of -yl)methyl)-2-butyl-5-((5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one}

1H-NMR (400MHz, CDCl3): 0.89 (3H, t), 1.32-1.70 (4H, m), 2.34 (3H, s), 2.64 (2H, t), 4.03 (2H, s), 5.23 (2H, s), 7.06-8.04 (12H, m) 1 H-NMR (400MHz, CDCl 3 ): 0.89 (3H, t), 1.32-1.70 (4H, m), 2.34 (3H, s), 2.64 (2H, t), 4.03 (2H, s), 5.23 ( 2H, s), 7.06-8.04 (12H, m)

실시예 B-12: 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-(4-메톡시벤질)-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온 {3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(4-methoxybenzyl)-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one}의 제조Example B-12: 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(4-methoxybenzyl) -1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidine-4(3H)-one {3-((2'-(1H-tetrazol-5-yl)biphenyl-4 Preparation of -yl)methyl)-2-butyl-5-((5-(4-methoxybenzyl)-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one}

1H-NMR (400MHz, CDCl3): 0.90 (3H, t), 1.33-1.72 (4H, m), 2.30 (3H, s), 2.67 (2H, t), 3.74 (3H, s), 3.92 (2H, s), 4.13 (2H, s), 5.18 (2H, s), 6.79-7.96 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.90 (3H, t), 1.33-1.72 (4H, m), 2.30 (3H, s), 2.67 (2H, t), 3.74 (3H, s), 3.92 ( 2H, s), 4.13 (2H, s), 5.18 (2H, s), 6.79-7.96 (12H, m)

실시예 B-13: 3-((2'-(1H-테트라졸-5-일)바이페닐-4-일)메틸)-2-부틸-5-((5-(4-클로로벤질)-1,2,4-옥사다이아졸-3-일)메틸)-6-메틸피리미딘-4(3H)-온 {3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(4-chlorobenzyl)-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one}의 제조Example B-13: 3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-5-((5-(4-chlorobenzyl)- 1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidine-4(3H)-one {3-((2'-(1H-tetrazol-5-yl)biphenyl-4- Preparation of yl)methyl)-2-butyl-5-((5-(4-chlorobenzyl)-1,2,4-oxadiazol-3-yl)methyl)-6-methylpyrimidin-4(3H)-one}

1H-NMR (400MHz, CDCl3): 0.91 (3H, t), 1.35-1.74 (4H, m), 2.32 (3H, s), 2.70 (2H, t), 3.94 (2H, s), 4.19 (2H, s), 5.20 (2H, s), 6.89-8.01 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.91 (3H, t), 1.35-1.74 (4H, m), 2.32 (3H, s), 2.70 (2H, t), 3.94 (2H, s), 4.19 ( 2H, s), 5.20 (2H, s), 6.89-8.01 (12H, m)

실시예 B-14: 메틸 4'-((2-부틸-5-((5-터트-부틸-1,2,4-옥사다이아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-카르복실레이트 {methyl 4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-carboxylate}의 제조 Example B-14: Methyl 4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol-3-yl)methyl)-4-methyl-6-ox Sopyrimidine-1(6H)-yl)methyl)biphenyl-2-carboxylate {methyl 4'-((2-butyl-5-((5-tert-butyl-1,2,4-oxadiazol- Preparation of 3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-carboxylate}

1H-NMR (400MHz, CDCl3): 0.90 (3H, t), 1.33-1.71 (13H, m), 2.35 (3H, s), 2.68 (2H, t), 3.62 (2H, s), 4.04 (2H, s), 5.37 (2H, s), 7.20-7.83 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): 0.90 (3H, t), 1.33-1.71 (13H, m), 2.35 (3H, s), 2.68 (2H, t), 3.62 (2H, s), 4.04 ( 2H, s), 5.37 (2H, s), 7.20-7.83 (8H, m)

실시예Example C-1: 3-(4'-((2-부틸-4-이소프로필-5-((5- C-1: 3-(4'-((2-butyl-4-isopropyl-5-((5- 메틸methyl -1,3,4--1,3,4- 옥사다이아졸Oxadiazole -2-일)-2 days) 메틸methyl )-6-)-6- 옥소피리미딘Oxopyrimidine -1(6H)-일)-1(6H)-day) 메틸methyl )) 바이페닐Biphenyl -2-일)-1,2,4--2-day)-1,2,4- 옥사다이아졸Oxadiazole -5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 -5(4H)-one {3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin Preparation of -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

[단계 1] 2-(2-부틸-4-이소프로필-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리디민-5-일)아세트산 {2-(2-butyl-4-isopropyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetic acid}의 제조[Step 1] 2-(2-butyl-4-isopropyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3 -Yl)biphenyl-4-yl)methyl)-1,6-dihydropyridinamine-5-yl)acetic acid {2-(2-butyl-4-isopropyl-6-oxo-1-((2'- Preparation of (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetic acid}

Figure 112018068967010-pat00048
Figure 112018068967010-pat00048

플라스크에 메틸 2-(2-부틸-4-이소프로필-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세테이트 (5.9 g, 11.7 mmol)을 투입하고, 메틸알콜 50 mL를 주입하였다. 온도를 15 ℃ 이하로 유지하며 2.5N 수산화나트륨 수용액 10 mL를 적가하고, 15 시간 동안 실온 교반하였다. 실온 교반을 완료한 후 감압농축하고, 클로로포름 150 mL와 정제수 150 mL을 주입하였다. 2N 염산 수용액을 적가하여 pH를 3~4로 조절하고, 클로로포름층을 분리하였다. 분리한 클로로포름층을 정제수 150 mL로 세척하고, 마그네슘설페이트 1 g으로 건조한 후 여과하여 농축하였다. 잔사를 1:2 에틸아세테이트/n-헥산을 60 mL를 사용하여 미황색 고체의 표제 화합물 4.2 g (수율: 75.7 %)을 얻었다.To the flask, methyl 2-(2-butyl-4-isopropyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- 1) Biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetate (5.9 g, 11.7 mmol) was added and 50 mL of methyl alcohol was injected. While maintaining the temperature at 15° C. or less, 10 mL of a 2.5N aqueous sodium hydroxide solution was added dropwise, followed by stirring at room temperature for 15 hours. After completing room temperature stirring, the mixture was concentrated under reduced pressure, and 150 mL of chloroform and 150 mL of purified water were injected. 2N hydrochloric acid aqueous solution was added dropwise to adjust the pH to 3-4, and the chloroform layer was separated. The separated chloroform layer was washed with 150 mL of purified water, dried over 1 g of magnesium sulfate, filtered and concentrated. The residue was obtained by using 4.2 mL of 1:2 ethyl acetate/n-hexane to obtain 4.2 g (yield: 75.7%) of the title compound as a pale yellow solid.

[단계 2] N'-아세틸-2-(2-부틸-4-이소프로필-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리디민-5-일)아세토하이드라자이드 {N'-acetyl-2-(2-butyl-4-isopropyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetohydrazide}의 제조[Step 2] N'-acetyl-2-(2-butyl-4-isopropyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4- Oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyridinamine-5-yl)acetohydrazide {N'-acetyl-2-(2-butyl-4- isopropyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin Preparation of -5-yl)acetohydrazide}

Figure 112018068967010-pat00049
Figure 112018068967010-pat00049

플라스크에 단계 1에서 제조된 화합물 (140 mg, 0.2 mmol)을 투입하고, 클로로포름 5 mL를 주입하였다. 온도를 15 ℃ 이하로 유지하며 디메틸아미노프로필 에틸카보디이미드 염산염 (44 mg, 0.22 mmol), 하이드록시벤조트리아졸 (29.6 mg, 0.22 mmol), 아세틸하이드라자이드 (16.9 mg, 0.22 mmol)을 투입한 후, 트리에틸아민 (22 mg, 0.22 mmol)를 적가하고 15 시간 동안 실온 교반하였다. 클로로포름 15 mL와 정제수 15 mL을 가하여 유기층을 분리하였다. 분리한 유기층을 마그네슘설페이트 1 g으로 건조한 후 여과하고 농축하여 표제 화합물 95 mg (수율: 62.5 %)을 얻었다.The compound prepared in Step 1 (140 mg, 0.2 mmol) was added to the flask, and 5 mL of chloroform was injected. Maintain the temperature below 15 ℃ and add dimethylaminopropyl ethylcarbodiimide hydrochloride (44 mg, 0.22 mmol), hydroxybenzotriazole (29.6 mg, 0.22 mmol), acetylhydrazide (16.9 mg, 0.22 mmol) After that, triethylamine (22 mg, 0.22 mmol) was added dropwise and stirred for 15 hours at room temperature. The organic layer was separated by adding 15 mL of chloroform and 15 mL of purified water. The separated organic layer was dried over 1 g of magnesium sulfate, filtered and concentrated to give 95 mg (yield: 62.5 %) of the title compound.

[단계 3] 3-(4'-((2-부틸-4-이소프로필-5-((5-메틸-1,3,4-옥사다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 [Step 3] 3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-6-oxopy Rimidine-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl-4 -isopropyl-5-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2, Preparation of 4-oxadiazol-5(4H)-one}

Figure 112018068967010-pat00050
Figure 112018068967010-pat00050

단계 2에서 제조된 화합물 (0.02 g)을 톨루엔 3 mL에 녹인 후, POCl3 (0.1 mL)를 적가하였다. 상온에서 10 분간 교반 후, 80 ℃에서 4 시간 동안 가열 교반하였다. 얼음물 10mL를 적가하고, 에틸아세테이트 20 mL로 희석하였다. 상온으로 승온시킨 후, NaHCO3 포화 수용액으로 세척하였다. 유기층을 무수 Na2SO4로 건조하고 감압 농축하였다. 크로마토그래피 (99:3 클로로포름/메틸알콜)로 정제하여 미색 고체의 표제 화합물 8.5 mg (수율: 43 %)을 얻었다.After dissolving the compound (0.02 g) prepared in Step 2 in 3 mL of toluene, POCl 3 (0.1 mL) was added dropwise. After stirring at room temperature for 10 minutes, the mixture was heated and stirred at 80°C for 4 hours. 10 mL of ice water was added dropwise, and diluted with 20 mL of ethyl acetate. After heating to room temperature, it was washed with saturated aqueous NaHCO 3 solution. The organic layer was dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. Purification by chromatography (99:3 chloroform/methyl alcohol) gave 8.5 mg (yield: 43%) of the title compound as an off-white solid.

1H-NMR (400MHz, CDCl3): δ 0.92 (m, 3H), 1.26 (d, 6H), 1.42 (m, 2H), 1.77 (m, 2H), 2.47 (s, 3H), 2.71 (t, 2H), 3.19 (q, 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 (m, 2H), 7.62 (t, 1H) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (m, 3H), 1.26 (d, 6H), 1.42 (m, 2H), 1.77 (m, 2H), 2.47 (s, 3H), 2.71 (t , 2H), 3.19 (q, 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 (m, 2H), 7.62 (t, 1H)

<실시예 C-2 내지 C-6><Examples C-2 to C-6>

실시예 C-2 내지 C-6의 화합물은 실시예 C-1과 유사한 방법으로 각 실시예에 상응하는 하이드라자이드 유도체 화합물을 이용하여 합성하였다.The compounds of Examples C-2 to C-6 were synthesized using a hydrazide derivative compound corresponding to each example in a similar manner to Example C-1.

실시예 C-2: 3-(4'-((2-부틸-4-이소프로필-5-((5-(4-메톡시페닐)-1,3,4-옥사다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-5-((5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example C-2: 3-(4'-((2-butyl-4-isopropyl-5-((5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl )Methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-4-isopropyl-5-((5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

1H-NMR (400MHz, CDCl3): δ 0.94 (t, 3H), 1.24 (d, 6H), 1.38 (m, 2H), 1.75 (m, 2H), 2.72 (t, 2H), 3.33 (q, 1H), 3.70 (s, 3H), 3.81 (s, 2H), 5.40 (s, 2H), 7.04 (t, 1H), 7.23-7.35 (m, 3H), 7.45 (d, 2H), 7.52 (m, 3H), 7.50 (m, 2H), 7.72 (t, 1H) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.94 (t, 3H), 1.24 (d, 6H), 1.38 (m, 2H), 1.75 (m, 2H), 2.72 (t, 2H), 3.33 (q , 1H), 3.70 (s, 3H), 3.81 (s, 2H), 5.40 (s, 2H), 7.04 (t, 1H), 7.23-7.35 (m, 3H), 7.45 (d, 2H), 7.52 ( m, 3H), 7.50 (m, 2H), 7.72 (t, 1H)

실시예 C-3: 3-(4'-((2-부틸-4-이소프로필-5-((5-(3-메톡시페닐)-1,3,4-옥사다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-5-((5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example C-3: 3-(4'-((2-butyl-4-isopropyl-5-((5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl )Methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-4-isopropyl-5-((5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

1H-NMR (400MHz, CDCl3): δ 0.91 (t, 3H), 1.24 (d, 6H), 1.39 (m, 2H), 1.78 (m, 2H), 2.71 (t, 2H), 3.33 (q, 1H), 3.67 (s, 3H), 3.94 (s, 2H), 5.31 (s, 2H), 6.94 (t, 2H), 7.21 (d, 2H), 7.23-7.35 (m, 4H), 7.45 (d, 2H), 7.79 (t, 2H) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (t, 3H), 1.24 (d, 6H), 1.39 (m, 2H), 1.78 (m, 2H), 2.71 (t, 2H), 3.33 (q , 1H), 3.67 (s, 3H), 3.94 (s, 2H), 5.31 (s, 2H), 6.94 (t, 2H), 7.21 (d, 2H), 7.23-7.35 (m, 4H), 7.45 ( d, 2H), 7.79 (t, 2H)

실시예 C-4: 3-(4'-((2-부틸-5-((5-하이드록시-1,3,4-옥사다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-hydroxy-1,3,4-oxadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example C-4: 3-(4'-((2-butyl-5-((5-hydroxy-1,3,4-oxadiazol-2-yl)methyl)-4-isopropyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2- butyl-5-((5-hydroxy-1,3,4-oxadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1 Preparation of ,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 1.26 (d, 6H), 1.42 (m, 2H), 1.77 (m, 2H), 2.46 (s, 1H), 2.70 (t, 2H), 3.20 (q, 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 (m, 2H), 7.62 (t, 1H) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.26 (d, 6H), 1.42 (m, 2H), 1.77 (m, 2H), 2.46 (s, 1H), 2.70 (t, 2H), 3.20 (q , 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 (m, 2H), 7.62 (t, 1H)

실시예 C-5: 3-(4'-((2-부틸-5-((5-(다이메틸아미노)-1,3,4-옥사다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(dimethylamino)-1,3,4-oxadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example C-5: 3-(4'-((2-butyl-5-((5-(dimethylamino)-1,3,4-oxadiazol-2-yl)methyl)-4-iso Propyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((5-(dimethylamino)-1,3,4-oxadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2 Preparation of -yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 1.26 (d, 6H), 1.42 (m, 2H), 1.77 (m, 2H), 2.47 (s, 1H), 2.71 (t, 2H), 2.80-2.95 (6H, d), 3.19 (q, 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 (m, 2H), 7.62 (t, 1H) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.26 (d, 6H), 1.42 (m, 2H), 1.77 (m, 2H), 2.47 (s, 1H), 2.71 (t, 2H), 2.80-2.95 (6H, d), 3.19 (q, 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 ( m, 2H), 7.62 (t, 1H)

실시예 C-6: 3-(4'-((2-부틸-4-이소프로필-6-옥소-5-((5-(피롤리딘-1-일)-1,3,4-옥사다이아졸-2-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-6-oxo-5-((5-(pyrrolidin-1-yl)-1,3,4-oxadiazol-2-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example C-6: 3-(4'-((2-butyl-4-isopropyl-6-oxo-5-((5-(pyrrolidin-1-yl)-1,3,4-oxa Diazole-2-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one {3-(4 '-((2-butyl-4-isopropyl-6-oxo-5-((5-(pyrrolidin-1-yl)-1,3,4-oxadiazol-2-yl)methyl)pyrimidin-1(6H) Preparation of -yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 1.26 (d, 6H), 1.42 (m, 2H), 1.50-1.85 (m, 6H), 2.47 (s, 1H), 2.71 (t, 2H), 2.80-2.95 (4H, m), 3.19 (q, 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 (m, 2H), 7.62 (t, 1H) 1 H-NMR (400 MHz, CDCl 3 ): δ 1.26 (d, 6H), 1.42 (m, 2H), 1.50-1.85 (m, 6H), 2.47 (s, 1H), 2.71 (t, 2H), 2.80 -2.95 (4H, m), 3.19 (q, 1H), 4.33 (s, 2H), 5.37 (s, 2H), 7.23 (d, 2H), 7.36 (d, 2H), 7.45 (d, 1H), 7.50 (m, 2H), 7.62 (t, 1H)

실시예Example D-1: 3-(4'-((2-부틸-4- D-1: 3-(4'-((2-butyl-4- 메틸methyl -6-옥소-5-((5--6-oxo-5-((5- 페닐옥사졸Phenyloxazole -2-일)-2 days) 메틸methyl )피리미딘-1(6H)-일))Pyrimidine-1(6H)-yl) 메틸methyl )) 바이페닐Biphenyl -2-일)-1,2,4--2-day)-1,2,4- 옥사다이아졸Oxadiazole -5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((5-phenyloxazol-2-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의-5(4H)-one {3-(4'-((2-butyl-4-methyl-6-oxo-5-((5-phenyloxazol-2-yl)methyl)pyrimidin-1(6H)-yl )methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} 제조 Produce

[단계 1] 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)-N-(2-옥소-2-페닐에틸)아세트아마이드 {2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N-(2-oxo-2-phenylethyl)acetamide}의 제조[Step 1] 2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- 1)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N-(2-oxo-2-phenylethyl)acetamide {2-(2-butyl-4- methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin Preparation of -5-yl)-N-(2-oxo-2-phenylethyl)acetamide}

Figure 112018068967010-pat00051
Figure 112018068967010-pat00051

2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리디민-5-일)아세트산 (0.1g), HOBt (0.031 g, 1.1 eq), EDCI (0.046 g, 1.15 eq), 트리에틸아민 (0.088 ml, 3 eq), 2-아미노-1-페닐에타논 (0.047 g, 1.3 eq)을 메틸렌클로라이드 10 ml에 녹인 후, 상온에서 18 시간 동안 교반하였다. 메틸렌클로라이드 10 ml를 첨가 하고 정제수 10 ml로 세척하였다. 물층을 메틸렌클로라이드 10 ml로 추출하였다. 유기층을 모아 무수 MgSO4로 건조, 여과 후 감압농축하였다. 남은 유기물을 실리카와 5% MeOH/CHCl3로 정제하여 표제 화합물 0.095 g을 수득하였다.2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl -4-yl)methyl)-1,6-dihydropyridinamine-5-yl)acetic acid (0.1 g), HOBt (0.031 g, 1.1 eq), EDCI (0.046 g, 1.15 eq), triethylamine (0.088 ml, 3 eq), 2-amino-1-phenylethanone (0.047 g, 1.3 eq) was dissolved in 10 ml of methylene chloride, and stirred at room temperature for 18 hours. 10 ml of methylene chloride was added and washed with 10 ml of purified water. The water layer was extracted with 10 ml methylene chloride. The combined organic layers were dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The remaining organic material was purified by silica and 5% MeOH/CHCl 3 to obtain 0.095 g of the title compound.

[단계 2] 3-(4'-((2-부틸-4-메틸-6-옥소-5-((5-페닐옥사졸-2-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-6-oxo-5-((5-phenyloxazol-2-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 [Step 2] 3-(4'-((2-butyl-4-methyl-6-oxo-5-((5-phenyloxazol-2-yl)methyl)pyrimidin-1(6H)-yl) Methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl-4-methyl-6-oxo-5-( Preparation of (5-phenyloxazol-2-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

Figure 112018068967010-pat00052
Figure 112018068967010-pat00052

단계 1에서 제조된 화합물 (0.095 g) 을 아세토나이트릴 10 ml에 녹인 후, POCl3 (0.03 ml, 2 eq) 를 적가하고, 18 시간 동안 환류 교반하였다. 반응 용액을 감압 농축 후 CHCl3 25 ml에 용해시켰다. 정제수 25 ml로 세척 후, 포화 NaHCO3 수용액 10 ml로 세척하였다. 유기층을 MgSO4 건조, 여과 후 감압 농축하였다. 남은 유기물을 실리카와 5% MeOH/CHCl3로 정제하여 표제 화합물 0.060 g (수율: 65 %)을 수득하였다.After dissolving the compound (0.095 g) prepared in Step 1 in 10 ml of acetonitrile, POCl 3 (0.03 ml, 2 eq) was added dropwise and stirred at reflux for 18 hours. The reaction solution was concentrated under reduced pressure and dissolved in 25 ml of CHCl 3 . After washing with 25 ml of purified water, it was washed with 10 ml of saturated NaHCO 3 aqueous solution. The organic layer was dried over MgSO 4 , filtered and concentrated under reduced pressure. The remaining organic material was purified by silica and 5% MeOH/CHCl 3 to obtain 0.060 g (yield: 65%) of the title compound.

1H-NMR (400MHz, CDCl3): δ 0.92 (3H, t), 1.37-1.76 (4H, m), 2.39 (3H, s), 2.71 (2H, t), 4.09 (2H, s), 5.31 (2H, s), 7.20-7.84 (14H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, t), 1.37-1.76 (4H, m), 2.39 (3H, s), 2.71 (2H, t), 4.09 (2H, s), 5.31 (2H, s), 7.20-7.84 (14H, m)

실시예 D-2: 3-(4'-((5-(벤조[d]옥사졸-2-일메틸)-2-부틸-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-(benzo[d]oxazol-2-ylmethyl)-2-butyl-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example D-2: 3-(4'-((5-(benzo[d]oxazol-2-ylmethyl)-2-butyl-4-isopropyl-6-oxopyrimidine-1(6H) -Yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-(benzo[d]oxazol-2-ylmethyl )-2-butyl-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

실시예 D-2의 화합물은 실시예 D-1과 유사한 방법으로 2-아미노-1-페닐에타논 대신 1-아미노페놀을 사용하여 합성하였다.The compound of Example D-2 was synthesized using 1-aminophenol instead of 2-amino-1-phenylethanone in a similar manner to Example D-1.

1H-NMR (400MHz, CDCl3): δ 0.93 (3H, t), 1.24 (6H, d), 1.37-1.76 (4H, m), 2.71 (2H, t), 3.34 (1H, m), 4.09 (2H, s), 5.31(2H, s), 7.20-7.84 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.93 (3H, t), 1.24 (6H, d), 1.37-1.76 (4H, m), 2.71 (2H, t), 3.34 (1H, m), 4.09 (2H, s), 5.31 (2H, s), 7.20-7.84 (12H, m)

실시예 D-3: 3-(4'-((5-((5-벤질이소옥사졸-3-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((5-benzylisoxazol-3-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조 Example D-3: 3-(4'-((5-((5-benzylisooxazol-3-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidine-1(6H) -Yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-((5-benzylisoxazol-3-yl) Preparation of methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

[단계 1] 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)-N-메톡시-N-메틸아세트아마이드 {2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N-methoxy-N-methylacetamide}의 제조[Step 1] 2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- 1)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N-methoxy-N-methylacetamide {2-(2-butyl-4-methyl-6- oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl )-N-methoxy-N-methylacetamide}

Figure 112018068967010-pat00053
Figure 112018068967010-pat00053

플라스크에 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세트산 5 g (10.5 mmol), (벤조트리아졸-1-일옥시)트리스(다이메틸아미노)포스포늄 헥사플루오로포스페이트 (BOP) 5.6 g (12.6 mmol)을 넣고, 메틸렌클로라이드 20 ml, 트리에틸아민 4.4 ml (31.5 mmol) 및 N,O-다이메틸하이드록실아민 670 mg (11.0 mmol)을 첨가 후, 혼합물을 12 시간 동안 상온에서 교반 후 감압 농축하였다. 남은 여액에 에틸아세테이트 100 ml를 넣고 포화 NH4Cl 수용액과 brine으로 순차적으로 세척하였다. 무수 MgSO4로 유기층을 건조하여 여과한 후, 여액을 농축하였다. 얻어진 표제 화합물은 별도의 정제 없이 다음 반응을 진행하였다 (수율: 100 %).2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) in a flask) Biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetic acid 5 g (10.5 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexa After adding 5.6 g (12.6 mmol) of fluorophosphate (BOP), 20 ml of methylene chloride, 4.4 ml (31.5 mmol) of triethylamine and 670 mg (11.0 mmol) of N,O-dimethylhydroxylamine were added, and then the mixture was added. The mixture was stirred at room temperature for 12 hours, and then concentrated under reduced pressure. 100 ml of ethyl acetate was added to the remaining filtrate, and washed sequentially with saturated aqueous NH 4 Cl solution and brine. The organic layer was dried over anhydrous MgSO 4 , filtered, and the filtrate was concentrated. The title compound obtained was subjected to the next reaction without further purification (yield: 100%).

[단계 2] 2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세트알데하이드 {2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetaldehyde}의 제조[Step 2] 2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3- 1)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetaldehyde {2-(2-butyl-4-methyl-6-oxo-1-((2'- Preparation of (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetaldehyde}

Figure 112018068967010-pat00054
Figure 112018068967010-pat00054

단계 1에서 제조된 화합물 4.8 g (10.5 mmol)에 THF 40 ml를 주입한 후, 질소 충전하였다. 반응액을 0 ℃로 냉각한 후 DIBAL-H 1.0 M THF 용액 10.5 mL (10.5 mmol)를 서서히 적가하였다. 0 ℃를 유지하면서 1 시간 동안 교반하였다. 반응액을 농축한 후, 에틸아세테이트 100 ml를 넣고 1N-HCl과 brine으로 순차적으로 세척하였다. 무수 MgSO4로 유기층을 건조하여 여과한 후, 여액을 감압 농축하였다. silica 와 CHCl3/MeOH=95/5)으로 분리 정제하여 표제 화합물 1.9 g을 수득하였다 (2 step 20%).40 ml of THF was injected into 4.8 g (10.5 mmol) of the compound prepared in Step 1, followed by nitrogen charging. After the reaction solution was cooled to 0° C., 10.5 mL (10.5 mmol) of DIBAL-H 1.0 M THF solution was slowly added dropwise. The mixture was stirred for 1 hour while maintaining 0°C. After the reaction solution was concentrated, 100 ml of ethyl acetate was added and washed sequentially with 1N-HCl and brine. The organic layer was dried over anhydrous MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. Separately purified with silica and CHCl3/MeOH=95/5) to give 1.9 g of the title compound (2 step 20%).

[단계 3] (E)-2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세트알데하이드 옥심 {(E)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetaldehyde oxime}의 제조[Step 3] (E)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazia) Zol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetaldehyde oxime {(E)-2-(2-butyl-4-methyl-6- oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl )acetaldehyde oxime}

Figure 112018068967010-pat00055
Figure 112018068967010-pat00055

플라스크에 단계 2에서 제조된 화합물 400 mg (0.87 mmol)을 넣고, THF 7 ml, 정제수 4 ml를 넣은 후, NH2OH 용액을 주입하였다. 12 시간 동안 상온에서 교반 후, 반응액을 감압 농축하였다. 여액에 에틸아세테이트 30 ml를 넣고 1N-HCl과 brine으로 순차적으로 세척하였다. 무수 MgSO4로 유기층을 건조하여 여과한 후, 여액을 농축하였다. 실리카와 CHCl3/MeOH=95/5로 정제하여 표제 화합물 150 mg (수율: 37 %)을 수득하였다.400 mg (0.87 mmol) of the compound prepared in Step 2 was added to the flask, 7 ml of THF and 4 ml of purified water were added, and then an NH 2 OH solution was injected. After stirring at room temperature for 12 hours, the reaction solution was concentrated under reduced pressure. 30 ml of ethyl acetate was added to the filtrate and washed sequentially with 1N-HCl and brine. The organic layer was dried over anhydrous MgSO 4 , filtered, and the filtrate was concentrated. Purification with silica and CHCl 3 /MeOH=95/5 gave 150 mg (yield: 37%) of the title compound.

[단계 4] (Z)-2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)-N-하이드록시아세트이미도일 클로라이드 {(Z)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N-hydroxyacetimidoyl chloride}의 제조[Step 4] (Z)-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiadia) Zol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)-N-hydroxyacetamidoyl chloride {(Z)-2-(2-butyl- 4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6 Preparation of -dihydropyrimidin-5-yl)-N-hydroxyacetimidoyl chloride}

Figure 112018068967010-pat00056
Figure 112018068967010-pat00056

단계 3에서 제조된 화합물 30 mg (0.063 mmol)에 CHCl3 3ml를 넣었다. 질소 충전 후 피리딘 100 mg (excess)을 주입하고, 1 시간 동안 환류 교반하였다. N-클로로숙신이미드 9.3 mg (0.07 mmol)을 넣고 2 시간 동안 환류 교반하였다. TLC, MS 를 사용하여 클로로화 반응을 확인한 후, 연속해서 다음 반응을 진행하였다. 3 ml of CHCl 3 was added to 30 mg (0.063 mmol) of the compound prepared in Step 3. After nitrogen filling, 100 mg (excess) of pyridine was injected, and stirred at reflux for 1 hour. 9.3 mg (0.07 mmol) of N-chlorosuccinimide was added and stirred at reflux for 2 hours. After confirming the chloroation reaction using TLC and MS, the next reaction was continuously performed.

[단계 5] 3-(4'-((5-((5-벤질이소옥사졸-3-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((5-benzylisoxazol-3-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조[Step 5] 3-(4'-((5-((5-benzylisooxazol-3-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl )Methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-((5-benzylisoxazol-3-yl)methyl) Preparation of -2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

Figure 112018068967010-pat00057
Figure 112018068967010-pat00057

단계 4에서 제조된 화합물 반응액에 3-페닐-1-프로핀 8.2 mg을 넣었다. 12 시간 동안 환류교반 후, 반응 용액을 감압 농축하였다. 남은 여액에 CHCl3 20 ml를 넣고 정제수로 세척하였다. 무수 MgSO4로 유기층을 건조하여 여과한 후, 여액을 감압 농축하였다. Prep-HPLC (아세토나이트릴 20 내지 100 %, gradient)로 정제하여 표제 화합물 3.6 mg을 수득하였다.8.2 mg of 3-phenyl-1-propine was added to the reaction solution prepared in step 4. After stirring for 12 hours under reflux, the reaction solution was concentrated under reduced pressure. 20 ml of CHCl 3 was added to the remaining filtrate and washed with purified water. The organic layer was dried over anhydrous MgSO 4 , filtered, and the filtrate was concentrated under reduced pressure. Purification by Prep-HPLC (acetonitrile 20-100%, gradient) gave 3.6 mg of the title compound.

1H-NMR (400MHz, CDCl3): δ 0.90 (3H, t), 1.38 (2H, m), 1.66 (2H, s), 2.33 (3H, s), 2.65 (2H, t), 3.82 (2H, s), 4.00 (2H, s), 5.27 (2H, s), 5.83 (1H, s), 7.16-7.29 (9H, m), 7.39 (1H, d), 7.49 (1H, m), 7.60 (1H, m), 7.81 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.38 (2H, m), 1.66 (2H, s), 2.33 (3H, s), 2.65 (2H, t), 3.82 (2H , s), 4.00 (2H, s), 5.27 (2H, s), 5.83 (1H, s), 7.16-7.29 (9H, m), 7.39 (1H, d), 7.49 (1H, m), 7.60 ( 1H, m), 7.81 (1H, d)

실시예 D-4: 3-(4'-((2-부틸-5-((5-터트-부틸이소옥사졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-tert-butylisoxazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example D-4: 3-(4'-((2-butyl-5-((5-tert-butylisooxazol-3-yl)methyl)-4-methyl-6-oxopyrimidine-1( 6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl-5-((5- tert-butylisoxazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Manufacturing

실시예 D-4의 화합물은 실시예 D-3과 유사한 방법으로 3-페닐-1-프로핀 대신 3,3-다이메틸-1-부틴을 사용하여 합성하였다.The compound of Example D-4 was synthesized using 3,3-dimethyl-1-butyne instead of 3-phenyl-1-propine in a similar manner to Example D-3.

1H-NMR (400MHz, CDCl3): δ 0.90 (3H, t), 1.33-1.42 (11H, m), 1.64-1.73 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 4.05 (2H, s), 5,28 (2H, s), 7.17-7.78 (9H, m) 1 H-NMR (400MHz, CDCl 3 ): δ 0.90 (3H, t), 1.33-1.42 (11H, m), 1.64-1.73 (2H, m), 2.31 (3H, s), 2.67 (2H, t) , 4.05 (2H, s), 5,28 (2H, s), 7.17-7.78 (9H, m)

실시예 D-5: 3-(4'-((2-부틸-5-((5-(2-하이드록시프로판-2-일)이소옥사졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일l)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(2-hydroxypropan-2-yl)isoxazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example D-5: 3-(4'-((2-butyl-5-((5-(2-hydroxypropan-2-yl)isooxazol-3-yl)methyl)-4-methyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yll)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((5-(2-hydroxypropan-2-yl)isoxazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl )-1,2,4-oxadiazol-5(4H)-one}

실시예 D-5의 화합물은 실시예 D-3과 유사한 방법으로 3-페닐-1-프로핀 대신 2-메틸-3-부틴-2-올을 사용하여 합성하였다.The compound of Example D-5 was synthesized using 2-methyl-3-butyn-2-ol instead of 3-phenyl-1-propine in a similar manner to Example D-3.

1H-NMR (400 MHz, CDCl3) δ 0.90 (3H, t), 1.38 (2H, m), 1.52 (6H, s), 1.68 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 3.77 (2H, s), 5.24 (2H, s), 5.96 (1H, s), 7.15 (2H, d), 7.29 (2H, d), 7.41 (1H, d), 7.48 (1H, m), 7.61 (1H, m), 7.75 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ) δ 0.90 (3H, t), 1.38 (2H, m), 1.52 (6H, s), 1.68 (2H, m), 2.31 (3H, s), 2.67 (2H , t), 3.77 (2H, s), 5.24 (2H, s), 5.96 (1H, s), 7.15 (2H, d), 7.29 (2H, d), 7.41 (1H, d), 7.48 (1H, m), 7.61 (1H, m), 7.75 (1H, d)

실시예 D-6: 3-(4'-((2-부틸-5-((5-(1-하이드록시에틸)이소옥사졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(1-hydroxyethyl)isoxazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example D-6: 3-(4'-((2-butyl-5-((5-(1-hydroxyethyl)isooxazol-3-yl)methyl)-4-methyl-6-oxopy Rimidine-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl-5 -((5-(1-hydroxyethyl)isoxazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol Preparation of -5(4H)-one}

실시예 D-6의 화합물은 실시예 D-3과 유사한 방법으로 3-페닐-1-프로핀 대신 3-부틴-2-올을 사용하여 합성하였다.The compound of Example D-6 was synthesized using 3-butyn-2-ol instead of 3-phenyl-1-propine in a similar manner to Example D-3.

1H-NMR (400 MHz, CDCl3) δ 0.90 (3H, t), 1.38 (2H, m), 1.48 (2H, d), 1.68 (2H, m), 2.31 (3H, s), 2.67 (2H, t), 3.77 (2H, s), 4.88 (1H, q), 5.24 (2H, s), 5.99 (1H, s), 7.14 (2H, d), 7.29 (2H, d), 7.41 (1H, d), 7.50 (1H, m), 7.61 (1H, m), 7.75 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ) δ 0.90 (3H, t), 1.38 (2H, m), 1.48 (2H, d), 1.68 (2H, m), 2.31 (3H, s), 2.67 (2H , t), 3.77 (2H, s), 4.88 (1H, q), 5.24 (2H, s), 5.99 (1H, s), 7.14 (2H, d), 7.29 (2H, d), 7.41 (1H, d), 7.50 (1H, m), 7.61 (1H, m), 7.75 (1H, d)

실시예Example E-1: 3-(4'-((2-부틸-4- E-1: 3-(4'-((2-butyl-4- 메틸methyl -5-((5--5-((5- 메틸methyl -1,3,4--1,3,4- 싸이아다이아졸Thiadiazole -2-일)-2 days) 메틸methyl )-6-)-6- 옥소피리미딘Oxopyrimidine -1(6H)-일)-1(6H)-day) 메틸methyl )) 바이페닐Biphenyl -2-일)-1,2,4--2-day)-1,2,4- 옥사다이아졸Oxadiazole -5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조-5(4H)-one {3-(4'-((2-butyl-4-methyl-5-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyrimidin Preparation of -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

Figure 112018068967010-pat00058
Figure 112018068967010-pat00058

실시예 C-1의 단계 1 및 단계 2와 유사한 방법으로 제조된 N'-아세틸-2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리디민-5-일)아세토하이드라자이드 (35 mg, 0.045 mmol)를 플라스크에 투입하고 테트라하이드로퓨란 3 mL를 주입한 후, 로신 시약 (17 mg, 0.045 mmol)을 투입하였다. 4 시간 동안 환류 교반 후 감압 농축하여 용매를 제거하였다. 클로로포름 30 mL와 정제수 30 mL을 가하여 유기층을 분리하였다. 분리한 유기층을 정제수 30 mL로 세척하고, 마그네슘설페이트 0.1 g으로 건조한 후 여과하여 농축하였다. 잔사를 크로마토그래피 (99:3 클로로포름/메틸알콜)로 정제하여 미황색 고체의 표제 화합물 8.7 mg (수율: 36.7 %)을 얻었다.N'-acetyl-2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4) prepared in a similar manner to Step 1 and Step 2 of Example C-1 ,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyridinamine-5-yl)acetohydrazide (35 mg , 0.045 mmol) was added to the flask, and 3 mL of tetrahydrofuran was injected, followed by addition of a rosin reagent (17 mg, 0.045 mmol). After reflux stirring for 4 hours, the mixture was concentrated under reduced pressure to remove the solvent. The organic layer was separated by adding 30 mL of chloroform and 30 mL of purified water. The separated organic layer was washed with 30 mL of purified water, dried over 0.1 g of magnesium sulfate, filtered and concentrated. The residue was purified by chromatography (99:3 chloroform/methyl alcohol) to obtain 8.7 mg (yield: 36.7%) of the title compound as a pale yellow solid.

1H-NMR (400MHz, CDCl3): δ 0.89 (3H, t), 1.32-1.70 (4H, m), 2.39 (3H, s), 2.66-2.68 (5H, m), 4.20 (2H, s), 5.29 (2H, s), 7.14-7.76 (8H, m)) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.32-1.70 (4H, m), 2.39 (3H, s), 2.66-2.68 (5H, m), 4.20 (2H, s) , 5.29 (2H, s), 7.14-7.76 (8H, m))

<실시예 E-2 내지 E-12><Examples E-2 to E-12>

실시예 E-2 내지 E-12의 화합물은 실시예 E-1과 유사한 방법으로 각 실시예에 대응되는 출발물질과 하이드라자이드 유도체로부터 합성하였다.The compounds of Examples E-2 to E-12 were synthesized from starting materials and hydrazide derivatives corresponding to each Example in a similar manner to Example E-1.

실시예 E-2: 3-(4'-((2-부틸-5-((5-에틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-2: 3-(4'-((2-butyl-5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.88 (3H, t), 1.31-1.70 (7H, m), 2.38 (3H, s), 2.66 (2H, t), 2.99-3.04 (2H, m), 4.20 (2H, s), 5.29 (2H, s), 7.13-7.74 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.88 (3H, t), 1.31-1.70 (7H, m), 2.38 (3H, s), 2.66 (2H, t), 2.99-3.04 (2H, m) , 4.20 (2H, s), 5.29 (2H, s), 7.13-7.74 (8H, m)

실시예 E-3: 3-(4'-((2-부틸-5-((5-이소프로필-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-3: 3-(4'-((2-butyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2- butyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1 Preparation of ,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.90 (3H, t), 1.35-1.42 (8H, m), 1.64-1.71 (2H, m), 2.41 (3H, s), 2.69 (2H, t), 3.31-3.42 (1H, m), 4.23 (2H, s), 5.31 (2H, s), 7.17-7.77 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.90 (3H, t), 1.35-1.42 (8H, m), 1.64-1.71 (2H, m), 2.41 (3H, s), 2.69 (2H, t) , 3.31-3.42 (1H, m), 4.23 (2H, s), 5.31 (2H, s), 7.17-7.77 (8H, m)

실시예 E-4: 3-(4'-((2-부틸-5-((5-터트-부틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-4: 3-(4'-((2-butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2 -butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl )-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, t), 1.36-1.42 (11H, m), 1.65-1.73 (2H, m), 2.42 (3H, s), 2.71 (2H, t), 4.24 (2H, s), 5.34 (2H, s), 6.82-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.36-1.42 (11H, m), 1.65-1.73 (2H, m), 2.42 (3H, s), 2.71 (2H, t) , 4.24 (2H, s), 5.34 (2H, s), 6.82-7.78 (8H, m)

실시예 E-5: 3-(4'-((4-메틸-5-((5-(1-메틸사이클로프로필)-1,3,4-싸이아다이아졸-2-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((4-methyl-5-((5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-5: 3-(4'-((4-methyl-5-((5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl)methyl)- 6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'- ((4-methyl-5-((5-(1-methylcyclopropyl)-1,3,4-thiadiazol-2-yl)methyl)-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl) Preparation of biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.96 (5H, m), 1.24 (2H, t), 1.53 (3H, s), 1.74 (2H, m), 2.42 (3H, s), 2.65 (2H, t), 4.22 (2H, s), 5.32 (2H, s), 7.19 (2H, d), 7.29 (2H, d), 7.41 (1H, q), 7.49 (1H, t), 7.60 (1H, t), 7.80 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (5H, m), 1.24 (2H, t), 1.53 (3H, s), 1.74 (2H, m), 2.42 (3H, s), 2.65 (2H , t), 4.22 (2H, s), 5.32 (2H, s), 7.19 (2H, d), 7.29 (2H, d), 7.41 (1H, q), 7.49 (1H, t), 7.60 (1H, t), 7.80 (1H, d)

실시예 E-6: 3-(4'-((5-((5-사이클로프로필-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((5-cyclopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-6: 3-(4'-((5-((5-cyclopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-( (5-cyclopropyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1, Preparation of 2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.96 (3H, t), 1.06 (2H, m), 1.16 (2H, m), 1.74 (2H, m), 2.33 (1H, m), 2.42 (3H, s), 2.68 (2H, t), 4.22 (2H, s), 5.33 (2H, s), 7.20 (2H, d), 7.31 (2H, d), 7.43 (1H, q), 7.51 (1H, t), 7.63 (1H, t), 7.80 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, t), 1.06 (2H, m), 1.16 (2H, m), 1.74 (2H, m), 2.33 (1H, m), 2.42 (3H , s), 2.68 (2H, t), 4.22 (2H, s), 5.33 (2H, s), 7.20 (2H, d), 7.31 (2H, d), 7.43 (1H, q), 7.51 (1H, t), 7.63 (1H, t), 7.80 (1H, d)

실시예 E-7: 3-(4'-((5-((5-터트-부틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-7: 3-(4'-((5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo- 2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5- ((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl) Preparation of -1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.96 (3H, m), 1.43 (9H, s), 1.74 (2H, m), 2.44 (3H, s), 2.65 (2H, t), 4.26 (2H, s), 5.33 (2H, s), 7.19 (2H, d), 7.31 (2H, d), 7.40 (1H, q), 7.52 (1H, t), 7.62 (1H, t), 7.79 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.96 (3H, m), 1.43 (9H, s), 1.74 (2H, m), 2.44 (3H, s), 2.65 (2H, t), 4.26 (2H , s), 5.33 (2H, s), 7.19 (2H, d), 7.31 (2H, d), 7.40 (1H, q), 7.52 (1H, t), 7.62 (1H, t), 7.79 (1H, d)

실시예 E-8: 3-(4'-((2-부틸-5-((5-터트-부틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-8: 3-(4'-((2-butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-(( 2-butyl-5-((5-tert-butyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2- Preparation of yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, t), 1.20-1.40 (14H, m), 1.65-1.73 (2H, m), 2.71 (2H, t), 3.36 (q, 1H), 4.24 (2H, s), 5.34 (2H, s), 6.82-7.78 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.20-1.40 (14H, m), 1.65-1.73 (2H, m), 2.71 (2H, t), 3.36 (q, 1H) , 4.24 (2H, s), 5.34 (2H, s), 6.82-7.78 (8H, m)

실시예 E-9: 3-(4'-((2-부틸-5-((5-(3-플루오로페닐)-1,3,4-싸이아다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(3-fluorophenyl)-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-9: 3-(4'-((2-butyl-5-((5-(3-fluorophenyl)-1,3,4-thiadiazol-2-yl)methyl)- 4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4 '-((2-butyl-5-((5-(3-fluorophenyl)-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl) Preparation of methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, t), 1.21 (6H, d), 1.41 (2H, m), 1.77 (2H, m), 2.73 (2H, t), 3.37 (1H, q), 4.40 (2H, s), 5.34 (2H, s), 7.14 (1H, t), 7.19 (2H, d), 7.33 (2H, d), 7.39 (2H, m), 7.45 (1H, t), 7.49 (1H, t), 7.61 (2H, t), 7.84 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.21 (6H, d), 1.41 (2H, m), 1.77 (2H, m), 2.73 (2H, t), 3.37 (1H , q), 4.40 (2H, s), 5.34 (2H, s), 7.14 (1H, t), 7.19 (2H, d), 7.33 (2H, d), 7.39 (2H, m), 7.45 (1H, t), 7.49 (1H, t), 7.61 (2H, t), 7.84 (1H, d)

실시예 E-10: 3-(4'-((2-부틸-4-이소프로필-5-((5-메틸-1,3,4-싸이아다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-10: 3-(4'-((2-butyl-4-isopropyl-5-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2- butyl-4-isopropyl-5-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1 Preparation of ,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, m), 1.17 (6H, d), 1.34 (2H, m), 1.75 (2H, m), 2.67 (5H, m), 3.30 (1H, q), 4.27 (2H, s), 5.30 (2H, s), 7.18 (2H, d), 7.31 (2H, d), 7.44 (1H, d), 7.50 (1H, t), 7.62 (1H, t), 7.80 (1H, d) 1 H-NMR (400MHz, CDCl 3 ): δ 0.91 (3H, m), 1.17 (6H, d), 1.34 (2H, m), 1.75 (2H, m), 2.67 (5H, m), 3.30 (1H , q), 4.27 (2H, s), 5.30 (2H, s), 7.18 (2H, d), 7.31 (2H, d), 7.44 (1H, d), 7.50 (1H, t), 7.62 (1H, t), 7.80 (1H, d)

실시예 E-11: 3-(4'-((2-부틸-5-((5-에틸-1,3,4-싸이아다이아졸-2-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-11: 3-(4'-((2-butyl-5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2- butyl-5-((5-ethyl-1,3,4-thiadiazol-2-yl)methyl)-4-isopropyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1 Preparation of ,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.92 (3H, m), 1.19 (6H, d), 1.34 (5H, m), 1.76 (2H, m), 2.70 (2H, t), 3.06 (2H, t), 3.35 (1H, q), 4.29 (2H, s), 5.31 (2H, s), 7.21 (2H, d), 7.34 (2H, d), 7.43 (1H, d), 7.53 (1H, t), 7.61 (1H, t), 7.81 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, m), 1.19 (6H, d), 1.34 (5H, m), 1.76 (2H, m), 2.70 (2H, t), 3.06 (2H , t), 3.35 (1H, q), 4.29 (2H, s), 5.31 (2H, s), 7.21 (2H, d), 7.34 (2H, d), 7.43 (1H, d), 7.53 (1H, t), 7.61 (1H, t), 7.81 (1H, d)

실시예 E-12: 3-(4'-((2-부틸-4-이소프로필-5-((5-이소프로필-1,3,4-싸이아다이아졸-2-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-isopropyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example E-12: 3-(4'-((2-butyl-4-isopropyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2 -butyl-4-isopropyl-5-((5-isopropyl-1,3,4-thiadiazol-2-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)- Preparation of 1,2,4-oxadiazol-5(4H)-one}

1H-NMR (400MHz, CDCl3): δ 0.92 (3H, m), 1.16 (6H, d), 1.36 (8H, m), 1.74 (2H, m), 2.70 (2H, t), 3.30 (1H, q), 3.39 (1H, q), 4.28 (2H, s), 5.30 (2H, s), 7.20 (2H, d), 7.30 (2H, d), 7.43 (1H, d), 7.52 (1H, t), 7.61 (1H, t), 7.78 (1H, d) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.92 (3H, m), 1.16 (6H, d), 1.36 (8H, m), 1.74 (2H, m), 2.70 (2H, t), 3.30 (1H , q), 3.39 (1H, q), 4.28 (2H, s), 5.30 (2H, s), 7.20 (2H, d), 7.30 (2H, d), 7.43 (1H, d), 7.52 (1H, t), 7.61 (1H, t), 7.78 (1H, d)

실시예Example F-1: 3-(4'-((2-부틸-5-((5-(4- F-1: 3-(4'-((2-butyl-5-((5-(4- 플루오로페닐Fluorophenyl )-4H-1,2,4-)-4H-1,2,4- 트리아졸Triazole -3-일)-3 days) 메틸methyl )-4-)-4- 메틸methyl -6--6- 옥소피리미딘Oxopyrimidine -1(6H)-일)-1(6H)-day) 메틸methyl )) 바이페닐Biphenyl -2-일)-1,2,4--2-day)-1,2,4- 옥사다이아Oxadia 졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Sol-5(4H)-one {3-(4'-((2-butyl-5-((5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)- Preparation of 4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}

[단계 1] 4-플루오로벤즈이미드아마이드 (4-fluorobenzimidamide)의 제조[Step 1] Preparation of 4-fluorobenzimidamide

Figure 112018068967010-pat00059
Figure 112018068967010-pat00059

NH4Cl (0.4 g, 1.01 eq)를 톨루엔에 첨가 후, 0 ℃로 냉각한 혼합물에 트리메틸 알루미늄 (3.7 6mL, 1.01 eq)를 첨가하였다. 상온에서 2 시간 동안 교반 후 4-플루오로벤조나이트릴 (1.0 g, 1 eq)을 첨가하였다. 80 ℃에서 16 시간 동안 교반한 후, 상온으로 냉각하였다. SiO2, 메틸렌클로라이드 (10 mL)를 첨가한 후 상온에서 10 분간 교반하였다. 반응 혼합물을 셀라이트 필터를 통해 여과 후 MeOH (10 mL)로 세척하였다. 여과액을 농축 후 건조하여 표제 화합물 0.8 g을 얻어 다음 반응에 사용하였다.NH 4 Cl (0.4 g, 1.01 eq) was added to toluene, and trimethyl aluminum (3.7 6 mL, 1.01 eq) was added to the mixture cooled to 0°C. After stirring at room temperature for 2 hours, 4-fluorobenzonitrile (1.0 g, 1 eq) was added. After stirring at 80° C. for 16 hours, it was cooled to room temperature. After adding SiO 2 and methylene chloride (10 mL), the mixture was stirred at room temperature for 10 minutes. The reaction mixture was filtered through a celite filter and washed with MeOH (10 mL). The filtrate was concentrated and dried to obtain 0.8 g of the title compound, which was used in the next reaction.

[단계 2] 3-(4'-((2-부틸-5-((5-(4-플루오로페닐)-4H-1,2,4-트리아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조[Step 2] 3-(4'-((2-butyl-5-((5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

Figure 112018068967010-pat00060
Figure 112018068967010-pat00060

2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세트산 (0.2g)을 4-플루오로벤즈이미드아마이드 (0.20 g, 2.5 eq), HATU (0.18 g, 1.1 eq), DIPEA (0.22 ml, 3 eq) 와 함께 DMF 2 mL에 녹인 후, 상온에서 2 시간 동안 교반하였다. 반응 용액에 하이드라진 (0.04 ml, 1.5 eq)과 아세트산 (0.24 ml, 10 eq) 를 첨가하고 80 ℃에서 18 시간 동안 교반하였다. 상온으로 냉각하고 에틸아세테이트 (10 mL)로 희석한 후, 포화 NaHCO3 수용액 (10 mL)으로 세척하였다. 무수 Na2SO4로 건조 후 농축하였다. 5% MeOH/CHCl3와 실리카를 사용하여 정제하여 표제 화합물 0.029 g (수율: 11 %)을 수득하였다.2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl -4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetic acid (0.2 g) 4-fluorobenzimideamide (0.20 g, 2.5 eq), HATU (0.18 g, 1.1 eq) , Dissolved in 2 mL of DMF with DIPEA (0.22 ml, 3 eq), and stirred at room temperature for 2 hours. Hydrazine (0.04 ml, 1.5 eq) and acetic acid (0.24 ml, 10 eq) were added to the reaction solution and stirred at 80° C. for 18 hours. After cooling to room temperature and diluted with ethyl acetate (10 mL), washed with saturated NaHCO 3 aqueous solution (10 mL). It was dried over anhydrous Na 2 SO 4 and concentrated. Purification with 5% MeOH/CHCl 3 and silica gave 0.029 g (yield: 11%) of the title compound.

1H-NMR (400MHz, CDCl3): δ 0.89 (3H, t), 1.32-1.73 (4H, m), 2.48 (3H, s), 2.69 (2H, t), 4.01 (2H, s), 5.29 (2H, s), 6.94-7.81 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.32-1.73 (4H, m), 2.48 (3H, s), 2.69 (2H, t), 4.01 (2H, s), 5.29 (2H, s), 6.94-7.81 (12H, m)

실시예 F-2: 3-(4'-((2-부틸-5-((5-(2-플루오로페닐)-4H-1,2,4-트리아졸-3-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((5-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example F-2: 3-(4'-((2-butyl-5-((5-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)- 4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-5-((5-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl )methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

4-플루오로벤조나이트릴 대신 2-플루오로벤조나이트릴을 사용하여 실시예 F-1과 유사한 방법으로 합성하였다.It was synthesized in a similar manner to Example F-1 using 2-fluorobenzonitrile instead of 4-fluorobenzonitrile.

1H-NMR (400MHz, CDCl3): δ 0.87 (3H, t), 1.30-1.69 (4H, m), 2.39 (3H, s), 2.65 (2H, t), 3.99 (2H, s), 5.25 (2H, s), 6.98-7.94 (12H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87 (3H, t), 1.30-1.69 (4H, m), 2.39 (3H, s), 2.65 (2H, t), 3.99 (2H, s), 5.25 (2H, s), 6.98-7.94 (12H, m)

실시예 F-3: 3-(4'-((2-부틸-4-메틸-5-((3-메틸-1H-1,2,4-트리아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-methyl-1H-1,2,4-triazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example F-3: 3-(4'-((2-butyl-4-methyl-5-((3-methyl-1H-1,2,4-triazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((2-butyl -4-methyl-5-((3-methyl-1H-1,2,4-triazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)- Preparation of 1,2,4-oxadiazol-5(4H)-one}

Figure 112018068967010-pat00061
Figure 112018068967010-pat00061

2-(2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)아세트산 0.2 g, 아미딘 HCl 0.06 g (1.5 eq), HATU 0.176 g (1.1 eq), DIPEA 0.22 ml (3 eq)를 DMF 2ml 에 녹인 후 상온에서 3 시간 동안 교반하였다. 반응 용액에 50~60% 히드라진 수화물 0.04 ml (1.5 eq) 과 아세트산 0.24 ml (10 eq)를 첨가하고, 80 oC에서 3시간 동안 가열 교반하였다. 상온으로 냉각하고 에틸아세테이트 10 ml로 희석한 후, 포화 NaHCO3 수용액으로 세척하였다. 무수 Na2SO4로 건조하고 농축한 뒤, Prep-HPLC (아세토니트릴 30 내지 100%, gradient)로 정제하여 표제 화합물 3.1 mg을 수득하였다.2-(2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl -4-yl)methyl)-1,6-dihydropyrimidin-5-yl)acetic acid 0.2 g, amidine HCl 0.06 g (1.5 eq), HATU 0.176 g (1.1 eq), DIPEA 0.22 ml (3 eq) Was dissolved in 2 ml of DMF and stirred at room temperature for 3 hours. To the reaction solution, 0.04 ml (1.5 eq) of 50-60% hydrazine hydrate and 0.24 ml (10 eq) of acetic acid were added, and the mixture was heated and stirred at 80 ° C for 3 hours. After cooling to room temperature and diluted with 10 ml of ethyl acetate, it was washed with saturated aqueous NaHCO 3 solution. After drying and concentration with anhydrous Na 2 SO 4 , purification by Prep-HPLC (acetonitrile 30 to 100%, gradient) gave 3.1 mg of the title compound.

1H-NMR (400MHz, CDCl3): δ 0.91 (3H, t), 1.30-1.75 (4H, m), 2.14 (3H, s), 2.36 (3H, s), 2.65-2.74 (2H, m), 3.81 (2H, s), 5.24 (2H, s), 7.10-7.80 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.91 (3H, t), 1.30-1.75 (4H, m), 2.14 (3H, s), 2.36 (3H, s), 2.65-2.74 (2H, m) , 3.81 (2H, s), 5.24 (2H, s), 7.10-7.80 (8H, m)

실시예 F-4: 3-(4'-((2-부틸-4-메틸-5-((3-메틸-1-페닐-1H-1,2,4-트리아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-4-methyl-5-((3-methyl-1-phenyl-1H-1,2,4-triazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example F-4: 3-(4'-((2-butyl-4-methyl-5-((3-methyl-1-phenyl-1H-1,2,4-triazol-5-yl)methyl )-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-4-methyl-5-((3-methyl-1-phenyl-1H-1,2,4-triazol-5-yl)methyl)-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

히드라진 대신 페닐히드라진을 사용하여 실시예 F-3과 유사한 방법으로 표제 화합물을 제조하였다.The title compound was prepared in a similar manner to Example F-3 using phenylhydrazine instead of hydrazine.

1H-NMR (400MHz, CDCl3): δ 0.89 (3H, t), 1.27-1.67 (4H, m), 2.18 (3H, s), 2.30 (3H, s), 2.59 (2H, t), 3.94 (2H, s), 5.18 (2H, s), 7.11-7.70 (13H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.89 (3H, t), 1.27-1.67 (4H, m), 2.18 (3H, s), 2.30 (3H, s), 2.59 (2H, t), 3.94 (2H, s), 5.18 (2H, s), 7.11-7.70 (13H, m)

실시예 F-5: 3-(4'-((2-부틸-5-((1-부틸-3-메틸-1H-1,2,4-트리아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((1-butyl-3-methyl-1H-1,2,4-triazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example F-5: 3-(4'-((2-butyl-5-((1-butyl-3-methyl-1H-1,2,4-triazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((1-butyl-3-methyl-1H-1,2,4-triazol-5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

히드라진 대신 부틸히드라진을 사용하여 실시예 F-3과 유사한 방법으로 표제 화합물을 제조하였다.The title compound was prepared in a similar manner to Example F-3 using butylhydrazine instead of hydrazine.

1H-NMR (400MHz, CDCl3): δ 0.87-0.91 (6H, m), 1.22-1.72 (8H, m), 2.13 (3H, s), 2.37 (3H, s), 2.64 (2H, t), 3.89 (2H, s), 4.01 (2H, t), 5.25 (2H, s), 7.11-7.72 (8H, m) 1 H-NMR (400 MHz, CDCl 3 ): δ 0.87-0.91 (6H, m), 1.22-1.72 (8H, m), 2.13 (3H, s), 2.37 (3H, s), 2.64 (2H, t) , 3.89 (2H, s), 4.01 (2H, t), 5.25 (2H, s), 7.11-7.72 (8H, m)

실시예 F-6: 3-(4'-((2-부틸-5-((1-(4-플루오로벤질)-1H-1,2,3-트리아졸-4-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example F-6: 3-(4'-((2-butyl-5-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)- 4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-5-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl )methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

[단계 1] (4-((2-부틸-4-메틸-6-옥소-1,6-다이하이드로피리미딘-5-일)메틸)-1H-1,2,3-트리아졸-1-일)메틸 피발레이트 {(4-((2-butyl-4-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate}의 제조[Step 1] (4-((2-butyl-4-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazole-1- 1)Methyl pivalate ((4-((2-butyl-4-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl) Preparation of methyl pivalate}

Figure 112018068967010-pat00062
Figure 112018068967010-pat00062

반응 용기에 아지도메틸 피발레이트 0.85 g (5.36 mmol)을 투입하고, 정제수 7.5 mL와 BuOH 7.5 mL을 투입한 후 교반하였다. 2-부틸-6-메틸-5-(프로프-2-이닐)피리미딘-4(3H)-온 1 g (4.90 mmol), CuSO4 5H2O 0.06 g (0.25 mmol) 및 소듐 아스코르베이트 0.29 g (1.47 mmol)를 순서대로 첨가한 후, 상온에서 24 시간 동안 교반하였다. 생성된 고체를 여과 후, 정제수 7.5 mL와 BuOH 7.5 mL의 혼합용매로 세척하였다. 여과물을 감압 건조하여 표제 화합물을 수득하였다.0.85 g (5.36 mmol) of azidomethyl pivalate was added to the reaction vessel, 7.5 mL of purified water and 7.5 mL of BuOH were added and stirred. 2-butyl-6-methyl-5-(prop-2-ynyl)pyrimidine-4(3H)-one 1 g (4.90 mmol), CuSO 4 5H 2 O 0.06 g (0.25 mmol) and sodium ascorbate 0.29 g (1.47 mmol) was added in order, followed by stirring at room temperature for 24 hours. After filtering the resulting solid, it was washed with a mixed solvent of 7.5 mL of purified water and 7.5 mL of BuOH. The filtrate was dried under reduced pressure to obtain the title compound.

[단계 2] (4-((2-부틸-1-((2'-시아노바이페닐-4-일)메틸)-4-메틸-6-옥소-1,6-다이하이드로피리미딘-5-일)메틸)-1H-1,2,3-트리아졸-1-일)메틸 피발레이트 {(4-((2-butyl-1-((2'-cyanobiphenyl-4-yl)methyl)-4-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate}의 제조[Step 2] (4-((2-butyl-1-((2'-cyanobiphenyl-4-yl)methyl)-4-methyl-6-oxo-1,6-dihydropyrimidine-5- 1)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate {(4-((2-butyl-1-((2'-cyanobiphenyl-4-yl)methyl)-4 Preparation of -methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate}

Figure 112018068967010-pat00063
Figure 112018068967010-pat00063

반응 용기에 단계 1에서 제조된 화합물 1.28 g (3.54 mmol)을 투입하고, 에틸아세테이트 11.5 mL와 DMF 1.3 mL를 가한 후 교반하였다. 4'-(브로모메틸)-[1,1'-바이페닐]-2-카보나이트릴 1.16 g (4.25 mmol)과 LiH 0.04 g (4.60 mmol)을 첨가 후, 80 ℃에서 24 시간 동안 교반하였다. 반응물을 농축 후, CHCl3 10 mL와 정제수 10 mL를 첨가하였다. pH 7이 될 때까지 1N HCl을 첨가하였다. 유기층을 분리 후 수분을 제거하고 농축하였다. 컬럼 (에틸아세테이트:헥산=1:1, Rf: 0.3)을 통하여 분리하여 표제 화합물을 수득하였다.To the reaction vessel, 1.28 g (3.54 mmol) of the compound prepared in Step 1 was added, 11.5 mL of ethyl acetate and 1.3 mL of DMF were added, followed by stirring. 1.16 g (4.25 mmol) of 4'-(bromomethyl)-[1,1'-biphenyl]-2-carbonitrile and 0.04 g (4.60 mmol) of LiH were added, followed by stirring at 80°C for 24 hours. After the reaction was concentrated, 10 mL of CHCl 3 and 10 mL of purified water were added. 1N HCl was added until pH 7. After separating the organic layer, moisture was removed and concentrated. Separation through a column (ethyl acetate:hexane=1:1, Rf: 0.3) gave the title compound.

[단계 3] (Z)-(4-((2-부틸-1-((2'-(N'-하이드록시카브아미미도일)바이페닐-4-일)메틸)-4-메틸-6-옥소-1,6-다이하이드로피리미딘-5-일)메틸)-1H-1,2,3-트리아졸-1-일)메틸 피발레이트 {(Z)-(4-((2-butyl-1-((2'-(N'-hydroxycarbamimidoyl)biphenyl-4-yl)methyl)-4-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate}의 제조[Step 3] (Z)-(4-((2-butyl-1-((2'-(N'-hydroxycarbamidoyl)biphenyl-4-yl)methyl)-4-methyl-6 -Oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate {(Z)-(4-((2-butyl -1-((2'-(N'-hydroxycarbamimidoyl)biphenyl-4-yl)methyl)-4-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2, Preparation of 3-triazol-1-yl)methyl pivalate}

Figure 112018068967010-pat00064
Figure 112018068967010-pat00064

반응 용기에 NH4OH.HCl 1.57 g (22.55 mmol)을 투입 후, DMSO 11 mL를 첨가하였다. NaHCO3 2.74 g (32.63 mmol)을 첨가 후, 50 ℃에서 10 분간 교반하였다. 단계 2에서 제조된 화합물 1.39 g (2.51 mmol)을 DMSO 5mL에 용해 후 서서히 첨가하였다. 90 ℃에서 24 시간 동안 교반하였다. 상온에서 정제수 33 mL를 첨가 후 5 시간 동안 교반하였다. 고체 반응물을 여과하고 정제수 10 mL로 세척 후 감압 건조하였다. 수득물을 반응기에 넣고 에틸아세테이트 20 mL와 정제수 20 mL를 첨가 후 에틸아세테이트층을 수거하였다. 수분을 제거 후 농축하여 표제 화합물을 수득하였다.NH 4 OH.HCl 1.57 g (22.55 mmol) was added to the reaction vessel, and then 11 mL of DMSO was added. After adding 2.74 g (32.63 mmol) of NaHCO 3 , the mixture was stirred at 50° C. for 10 minutes. 1.39 g (2.51 mmol) of the compound prepared in Step 2 was dissolved in 5 mL of DMSO and then slowly added. Stir at 90° C. for 24 hours. After adding 33 mL of purified water at room temperature, the mixture was stirred for 5 hours. The solid reactant was filtered, washed with 10 mL of purified water, and dried under reduced pressure. The obtained product was placed in a reactor, and 20 mL of ethyl acetate and 20 mL of purified water were added, and then the ethyl acetate layer was collected. After removing moisture, it was concentrated to obtain the title compound.

[단계 4] (Z)-(4-((2-butyl-4-methyl-6-oxo-1-((2'-(N'-(phenoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate {(Z)-(4-((2-butyl-4-methyl-6-oxo-1-((2'-(N'-(phenoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate}의 제조[Step 4] (Z)-(4-((2-butyl-4-methyl-6-oxo-1-((2'-(N'-(phenoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)- 1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate {(Z)-(4-((2-butyl-4-methyl-6-oxo -1-((2'-(N'-(phenoxycarbonyloxy)carbamimidoyl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1 Preparation of -yl)methyl pivalate}

Figure 112018068967010-pat00065
Figure 112018068967010-pat00065

반응 용기에 단계 3에서 제조된 화합물 0.67 g (1.14 mmol)을 투입 후 CHCl3 7 mL를 첨가하여 용해하였다. 0 ℃로 냉각 후 트리메틸아민 0.35 mL (2.52 mmol)을 첨가하였다. 페닐 클로로포르메이트 0.22 mL (1.71 mmol)을 첨가하고, 0 ℃에서 30 분 교반 후 상온에서 24 시간 동안 교반하였다. 정제수 10 mL를 첨가 후 유기층을 분리하였다. 수분을 제거 후 농축하여 표제 화합물을 수득하였다.To the reaction vessel, 0.67 g (1.14 mmol) of the compound prepared in Step 3 was added, and 7 mL of CHCl 3 was added to dissolve it. After cooling to 0° C., 0.35 mL (2.52 mmol) of trimethylamine was added. 0.22 mL (1.71 mmol) of phenyl chloroformate was added, stirred at 0° C. for 30 minutes, and stirred at room temperature for 24 hours. After adding 10 mL of purified water, the organic layer was separated. After removing moisture, it was concentrated to give the title compound.

[단계 5] (4-((2-부틸-4-메틸-6-옥소-1-((2'-(5-옥소-4,5-다이하이드로-1,2,4-옥사다이아졸-3-일)바이페닐-4-일)메틸)-1,6-다이하이드로피리미딘-5-일)메틸)-1H-1,2,3-트리아졸-1-일)메틸 피발레이트 {(4-((2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate}의 제조[Step 5] (4-((2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole- 3-yl)biphenyl-4-yl)methyl)-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate {( 4-((2-butyl-4-methyl-6-oxo-1-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4- Preparation of yl)methyl)-1,6-dihydropyrimidin-5-yl)methyl)-1H-1,2,3-triazol-1-yl)methyl pivalate}

Figure 112018068967010-pat00066
Figure 112018068967010-pat00066

반응 용기에 단계 4에서 제조된 화합물 0.88 g (1.24 mmol)을 투입하고 톨루엔 6 mL를 첨가한 후, 110 ℃에서 24 시간 동안 교반하였다. 반응물을 농축후 에틸아세테이트 10 mL와 정제수 10 mL를 첨가 후 유기층을 분리하였다. 유기층의 수분을 제거 후 농축하였다. 에틸아세테이트 1.25 mL와 헥산 3.75 mL를 첨가 후, 상온에서 교반하였다. 고체 반응물을 여과 후 감압 건조하여 표제 화합물을 수득하였다.To the reaction vessel, 0.88 g (1.24 mmol) of the compound prepared in Step 4 was added, and 6 mL of toluene was added, followed by stirring at 110° C. for 24 hours. After the reaction was concentrated, 10 mL of ethyl acetate and 10 mL of purified water were added and the organic layer was separated. After removing moisture from the organic layer, it was concentrated. After adding 1.25 mL of ethyl acetate and 3.75 mL of hexane, the mixture was stirred at room temperature. The solid reactant was filtered and dried under reduced pressure to obtain the title compound.

[단계 6] 3-(4'-((5-((1H-1,2,3-트리아졸-4-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((5-((1H-1,2,3-triazol-4-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조[Step 6] 3-(4'-((5-((1H-1,2,3-triazol-4-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidine-1 (6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-((5-((1H-1,2 ,3-triazol-4-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5( Preparation of 4H)-one}

Figure 112018068967010-pat00067
Figure 112018068967010-pat00067

반응 용기에 단계 5에서 제조된 화합물 0.58 g (0.95 mmol)을 투입 후 정제수 3 mL와 MeOH 3 mL 첨가하여 교반하였다. NaOH 0.83 g (2.09 mmol)을 첨가하고 24 시간 동안 상온에서 교반하였다. 농축 후 CHCl3 10 mL와 정제수 10 mL를 첨가하고, pH 7이 될 때까지 1N HCl을 첨가하였다. 유기층을 분리 후 수분을 제거 후 농축하여 표제 화합물을 수득하였다.To the reaction vessel, 0.58 g (0.95 mmol) of the compound prepared in Step 5 was added, followed by stirring by adding 3 mL of purified water and 3 mL of MeOH. 0.83 g (2.09 mmol) of NaOH was added and stirred at room temperature for 24 hours. After concentration, 10 mL of CHCl 3 and 10 mL of purified water were added, and 1N HCl was added until pH 7 was reached. After separating the organic layer, the moisture was removed and concentrated to obtain the title compound.

[단계 7] 3-(4'-((2-부틸-5-((1-(4-플루오로벤질)-1H-1,2,3-트리아졸-4-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조[Step 7] 3-(4'-((2-butyl-5-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4'-( (2-butyl-5-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl )biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

Figure 112018068967010-pat00068
Figure 112018068967010-pat00068

반응 용기에 단계 6에서 제조된 화합물 100 mg (0.20 mmol)을 투입 후, 에틸아세테이트 1 mL를 첨가하였다. K2CO3 30 mg (0.22 mmol)과 4-플루오로벤질클로라이드 31 mg (0.21 mmol)을 첨가 후, 78 ℃에서 24 시간 동안 교반하였다. 반응물을 농축 후 CHCl3 10 mL와 정제수 10 mL를 첨가하였다. 유기층을 분리 후 수분을 제거하였다. 농축 후 컬럼으로 분리하여 (gradient H2O:아세토나이트릴 = 9:1

Figure 112018068967010-pat00069
0:10) 표제 화합물을 수득하였다.After adding 100 mg (0.20 mmol) of the compound prepared in Step 6 to the reaction vessel, 1 mL of ethyl acetate was added. 30 mg (0.22 mmol) of K 2 CO 3 and 31 mg (0.21 mmol) of 4-fluorobenzylchloride were added, followed by stirring at 78° C. for 24 hours. After the reaction was concentrated, 10 mL of CHCl 3 and 10 mL of purified water were added. After separating the organic layer, moisture was removed. After concentration, separation by column (gradient H 2 O:acetonitrile = 9:1
Figure 112018068967010-pat00069
0:10) The title compound was obtained.

1H-NMR (400 MHz, CDCl3): δ 7.78 (d, 1H), 7.74 (t, 1H), 7.55 (t, 1H), 7.46 (m, 3H), 7.39 (m, 1H), 7.28 (m, 5H), 7.27 (m, 1H), 6.83 (d, 1H), 5.24 (s, 2H), 3.95 (s, 2H), 3.87 (s, 2H), 2.69 (t, 2H), 2.35 (s, 3H), 1.68 (m, 2H), 1.38 (m, 2H), 0.88 (t, 3H) 1 H-NMR (400 MHz, CDCl 3 ): δ 7.78 (d, 1H), 7.74 (t, 1H), 7.55 (t, 1H), 7.46 (m, 3H), 7.39 (m, 1H), 7.28 ( m, 5H), 7.27 (m, 1H), 6.83 (d, 1H), 5.24 (s, 2H), 3.95 (s, 2H), 3.87 (s, 2H), 2.69 (t, 2H), 2.35 (s , 3H), 1.68 (m, 2H), 1.38 (m, 2H), 0.88 (t, 3H)

실시예 F-7: 3-(4'-((2-부틸-5-((1-(2-플루오로벤질)-1H-1,2,3-트리아졸-4-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온 {3-(4'-((2-butyl-5-((1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one}의 제조Example F-7: 3-(4'-((2-butyl-5-((1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)- 4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one {3-(4' -((2-butyl-5-((1-(2-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl )methyl)biphenyl-2-yl)-1,2,4-oxadiazol-5(4H)-one} Preparation

4-플루오로벤질클로라이드 대신 2-플루오로벤질클로라이드를 사용하여 실시예 F-6과 동일한 방법으로 표제 화합물을 제조하였다.The title compound was prepared in the same manner as in Example F-6 using 2-fluorobenzylchloride instead of 4-fluorobenzylchloride.

1H-NMR (400 MHz, CDCl3): δ 7.77 (d, 1H), 7.70 (t, 1H), 7.51 (t, 1H), 7.41 (m, 3H), 7.33 (m, 1H), 7.27 (m, 5H), 7.21 (m, 1H), 6.89 (d, 1H), 5.24 (s, 2H), 3.93 (s, 2H), 3.85 (s, 2H), 2.67 (t, 2H), 2.36 (s, 3H), 1.67 (m, 2H), 1.36 (m, 2H), 0.88 (t, 3H) 1 H-NMR (400 MHz, CDCl 3 ): δ 7.77 (d, 1H), 7.70 (t, 1H), 7.51 (t, 1H), 7.41 (m, 3H), 7.33 (m, 1H), 7.27 ( m, 5H), 7.21 (m, 1H), 6.89 (d, 1H), 5.24 (s, 2H), 3.93 (s, 2H), 3.85 (s, 2H), 2.67 (t, 2H), 2.36 (s , 3H), 1.67 (m, 2H), 1.36 (m, 2H), 0.88 (t, 3H)

실시예 A-1 내지 A-115, 실시예 B-1 내지 B-14, 실시예 C-1 내지 C-6, 실시예 D-1 내지 D-6, 실시예 E-1 내지 E-12, 실시예 F-1 내지 F-7에서 제조한 본 발명의 화합물들의 구조는 다음 표 1에 정리된 바와 같다.Examples A-1 to A-115, Examples B-1 to B-14, Examples C-1 to C-6, Examples D-1 to D-6, Examples E-1 to E-12, The structures of the compounds of the present invention prepared in Examples F-1 to F-7 are summarized in Table 1 below.

[표 1][Table 1]

Figure 112018068967010-pat00070
Figure 112018068967010-pat00070

Figure 112018068967010-pat00071
Figure 112018068967010-pat00071

Figure 112018068967010-pat00072
Figure 112018068967010-pat00072

Figure 112018068967010-pat00073
Figure 112018068967010-pat00073

Figure 112018068967010-pat00074
Figure 112018068967010-pat00074

Figure 112018068967010-pat00075
Figure 112018068967010-pat00075

Figure 112018068967010-pat00076
Figure 112018068967010-pat00076

Figure 112018068967010-pat00077
Figure 112018068967010-pat00077

Figure 112018068967010-pat00078
Figure 112018068967010-pat00078

Figure 112018068967010-pat00079
Figure 112018068967010-pat00079

Figure 112018068967010-pat00080
Figure 112018068967010-pat00080

Figure 112018068967010-pat00081
Figure 112018068967010-pat00081

Figure 112018068967010-pat00082
Figure 112018068967010-pat00082

Figure 112018068967010-pat00083
Figure 112018068967010-pat00083

Figure 112018068967010-pat00084
Figure 112018068967010-pat00084

Figure 112018068967010-pat00085
Figure 112018068967010-pat00085

Figure 112018068967010-pat00086
Figure 112018068967010-pat00086

Figure 112018068967010-pat00087
Figure 112018068967010-pat00087

Figure 112018068967010-pat00088
Figure 112018068967010-pat00088

Figure 112018068967010-pat00089
Figure 112018068967010-pat00089

<< 실험예Experimental Example 1> 1> 피오글리타존Pioglitazone 대비 활성도 측정 Contrast activity measurement

1. 실험 방법1. Experimental method

- 사용 세포: Cos-7 (Fibroblast-like cell line derived from monkey kidney tissue)-Cells used: Cos-7 (Fibroblast-like cell line derived from monkey kidney tissue)

- 사용 배지: Cos-7 cell_DMEM 10% FBS (DMEM : Invitrogen, #11995-065 or 073)-Medium used: Cos-7 cell_DMEM 10% FBS (DMEM: Invitrogen, #11995-065 or 073)

각 실시예의 화합물과 피오글리타존을 DMSO에 녹여 1 mM 농도의 용액을 제조한 후, 10 % FBS 배지로 희석하여 10 μM 농도의 용액으로 실험하였다.The compound of each example and pioglitazone were dissolved in DMSO to prepare a 1 mM concentration solution, and then diluted with 10% FBS medium and tested with a 10 μM concentration solution.

[Day-1][Day-1]

48 well plate에 세포를 3 X 104 cells / 250 μL / well 로 seeding 하고, 37 ℃, 5 % CO2 에서 24 시간 동안 incubation 하였다.Cells were seeded into 48 well plates at 3 X 10 4 cells / 250 μL / well, and incubated at 37°C and 5% CO 2 for 24 hours.

[Day-2][Day-2]

1) 상기 plate의 각 well을 PBS 0.5 mL로 2회 세척한 후, serum free media (DMEM) 250 μL씩 넣고 37 ℃, 5 % CO2 incubator에 넣어 두었다.1) After washing each well of the plate twice with 0.5 mL of PBS, 250 μL of serum free media (DMEM) was added and placed in a 37°C, 5% CO 2 incubator.

2) 다음의 Mix 1과 Mix 2를 각각 제조한 뒤, Mix 1과 Mix 2를 잘 섞고 5분간 실온에 두었다.2) After the following Mix 1 and Mix 2 were prepared, Mix 1 and Mix 2 were mixed well and left at room temperature for 5 minutes.

- Mix 1-Mix 1

Figure 112018068967010-pat00090
Figure 112018068967010-pat00090

- Mix 2-Mix 2

Figure 112018068967010-pat00091
Figure 112018068967010-pat00091

- Lipofectamine 3000 (Invitrogen, #L3000008)-Lipofectamine 3000 (Invitrogen, #L3000008)

- Opti-MEM media (Invitrogen, #L31985-070)-Opti-MEM media (Invitrogen, #L31985-070)

3) incubator에 넣어둔 plate에 잘 섞인 Mix 1과 Mix 2 를 well당 25 μL씩 넣고, 37 ℃, 5 % CO2 incubator에서 6 시간 동안 배양하였다.3) 25 μL per well of Mix 1 and Mix 2 mixed well in the plate placed in the incubator was added, and incubated at 37° C. in a 5% CO 2 incubator for 6 hours.

4) 상기 plate의 배양액을 제거한 후 각 well당 각 실시예의 화합물 용액을 250 μL씩 넣고, 37 ℃, 5 % CO2 incubator에서 20 시간 동안 배양하였다.4) After removing the culture solution of the plate, 250 μL of the compound solution of each example was added to each well, and cultured for 20 hours in a 37°C, 5% CO 2 incubator.

[Day-3][Day-3]

1) 48 well plate를 PBS로 1회 세척한 후 각 well에 65 μL씩 passive Lysis Buffer(PLB)를 넣고, 15 분 동안 80 rpm으로 shaking 한 뒤, e-tube로 옮겨 4 ℃, 13000 rpm에서 1 분 동안 원심분리하였다.1) After washing the 48 well plate once with PBS, add 65 μL of passive Lysis Buffer (PLB) to each well, shake at 80 rpm for 15 minutes, transfer to the e-tube, and move to 4°C at 13000 rpm 1 Centrifuge for minutes.

2) 상층액 20 μL를 white well plate로 옮기고, Luciferase buffer 100 μL를 각 well에 넣고 Luminometer 기기로 Firefly activity를 측정하였다.2) 20 μL of the supernatant was transferred to a white well plate, 100 μL of Luciferase buffer was added to each well, and firefly activity was measured with a Luminometer instrument.

3) Renilla로 보정하여 Firefly activity를 산정한 후, DMSO를 기준으로 PPARγ 활성도를 측정하였다.3) After calculating Firefly activity by correcting with Renilla, PPARγ activity was measured based on DMSO.

2. 실험 결과2. Experimental results

실험예 1의 결과는 다음 표 2에 기재한 바와 같다.The results of Experimental Example 1 are as shown in Table 2 below.

[표 2][Table 2]

Figure 112018068967010-pat00092
Figure 112018068967010-pat00092

Figure 112018068967010-pat00093
Figure 112018068967010-pat00093

<< 실험예Experimental Example 2> 2> 반수활성Half-water activity 농도( density( ECEC 5050 ) 및 ) And 최대활성Maximum activity (A(A maxmax ) 측정) Measure

1. 실험 방법1. Experimental method

Indigo 사에서 공급하는 Human PPAR gamma Reporter assay (Indigo, #IB00101) 킷을 사용하여 다음과 같은 방법으로 반수활성 농도(EC50)와 최대 활성(Amax)을 측정하였다.Using the Human PPAR gamma Reporter assay (Indigo, #IB00101) kit supplied by Indigo, hemi-activity concentration (EC 50 ) and maximum activity (A max ) were measured in the following manner.

상기 킷에서 제공하는 reporter 세포가 담긴 튜브에 상기 킷에서 제공하는 Cell Recovery Medium(CRM) 10 mL을 넣은 후 37 ℃ 수조에서 10 분간 유지한 뒤, 500 μL를 취하여 reporter 세포 생존율을 측정하고, 상기 킷에서 제공하는 plate에 100 μL씩 분주 후 세포배양기에 1 시간 동안 넣어두었다.After adding 10 mL of the Cell Recovery Medium (CRM) provided by the kit to a tube containing reporter cells provided by the kit, maintaining it in a 37° C. water bath for 10 minutes, taking 500 μL to measure reporter cell viability, and measuring the kit After dispensing 100 μL into the plate provided by, it was placed in a cell incubator for 1 hour.

상기 킷에서 제공하는 Compound Screening Medium(CSM) 20mL에 DMSO 20 μL를 넣어 0.1% DMSO in CSM 희석액을 만들고, 상기 희석액으로 각 실시예의 화합물을 희석하여 20, 10, 2.5, 0.625, 0.156, 0.039, 0.0009 μM 농도가 되도록 상기 plate에 처리하였다.20 μL of DMSO is added to 20 mL of Compound Screening Medium (CSM) provided by the kit to make a 0.1% DMSO in CSM dilution, and the compounds of each example are diluted with the dilutions to give 20, 10, 2.5, 0.625, 0.156, 0.039, 0.0009 The plate was treated to a concentration of μM.

상기 plate를 37℃, 5% CO2 배양기에서 22 내지 24 시간 동안 배양한 뒤, 상측액을 제거한 후 상기 킷에서 제공하는 Detection Substrate와 Detection Buffer를 1:1로 섞은 용액 100 μL를 각 well에 분주하고 5분 후 MDS사의 'SpectraMax L' Luminescence 장비로 흡광도를 측정하여 DMSO 값을 기준으로 보정한 후, Amax 값 및 EC50 값을 산출하였다.After incubating the plate for 22 to 24 hours in a 37°C, 5% CO 2 incubator, remove the supernatant and dispense 100 μL of the detection substrate and detection buffer provided in the kit 1:1 in each well. After 5 minutes, the absorbance was measured with MDS''SpectraMax L'Luminescence equipment, and then corrected based on the DMSO value, and then A max value and EC 50 value were calculated.

2. 실험 결과2. Experimental results

실험예 2의 결과는 다음 표 3에 기재한 바와 같다.The results of Experimental Example 2 are as shown in Table 3 below.

[표 3][Table 3]

Figure 112018068967010-pat00094
Figure 112018068967010-pat00094

Claims (8)

하기 화학식 I 로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염:
[화학식 I]
Figure 112020010691441-pat00095

상기 화학식 I 에서,
X 는
Figure 112020010691441-pat00125
이고,
Y 는 H, C1-C6 알킬, NR5R6, OR7, C4-C7 시클로알킬, C5-C10 스파이로 고리, C5-C10 바이사이클릭 고리, 4-7원 헤테로시클로알킬, 아릴 또는 헤테로아릴이고 {여기서, 상기 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C6 알킬, OR7, 할로 또는 C1-C6 할로알킬로 치환될 수 있음},
Z 는
Figure 112020010691441-pat00099
이고,
Ra1, Ra2, Rb1 및 Rb2 는 각각 독립적으로 H 이고,
R1 및 R2 는 각각 독립적으로 C1-C6 알킬이고,
R5 내지 R7 은 각각 독립적으로 H 또는 C1-C6 알킬이고,
L1 은 -(CH2)m- 이고 {여기서, 상기 -(CH2)m- 의 하나 이상의 H 는 중수소로 치환될 수 있음},
L2 는 -(CH2)n- 또는
Figure 112020010691441-pat00101
이고 {여기서, 상기 -(CH2)n- 및
Figure 112020010691441-pat00102
의 하나 이상의 H 는 C1-C6 알킬로 치환될 수 있음},
m 은 1 이고,
n 은 0, 1, 2 또는 3 이고,
p 는 2, 3 또는 4 이다.A compound represented by the formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof:
[Formula I]
Figure 112020010691441-pat00095

In the above formula I,
X is
Figure 112020010691441-pat00125
ego,
Y is H, C 1 -C 6 alkyl, NR 5 R 6 , OR 7 , C 4 -C 7 cycloalkyl, C 5 -C 10 spiro ring, C 5 -C 10 bicyclic ring, 4-7 membered Heterocycloalkyl, aryl or heteroaryl, wherein at least one H of the aryl or heteroaryl is C 1 -C 6 alkyl, OR 7 , Can be substituted with halo or C 1 -C 6 haloalkyl},
Z is
Figure 112020010691441-pat00099
ego,
R a1 , R a2 , R b1 and R b2 are each independently H,
R 1 and R 2 Are each independently C 1 -C 6 alkyl,
R 5 to R 7 are each independently H or C 1 -C 6 alkyl,
L 1 is -(CH 2 ) m- (wherein at least one H of -(CH 2 ) m -can be substituted with deuterium),
L 2 is -(CH 2 ) n -or
Figure 112020010691441-pat00101
And {where, -(CH 2 ) n -and
Figure 112020010691441-pat00102
At least one H of may be substituted with C 1 -C 6 alkyl},
m is 1,
n is 0, 1, 2 or 3,
p is 2, 3 or 4. 제 1 항에 있어서,
X 는
Figure 112020010691441-pat00126
이고,
Y 는 C1-C4 알킬, NR5R6, OR7, C4-C6 시클로알킬, C5-C10 스파이로 고리, C5-C10 바이사이클릭 고리, 4-6원 헤테로시클로알킬, 아릴 또는 헤테로아릴이고 {여기서, 상기 아릴 또는 헤테로아릴의 하나 이상의 H는 C1-C4 알킬, OR7, 할로 또는 C1-C4 할로알킬로 치환될 수 있음},
Z 는
Figure 112020010691441-pat00106
이고,
Ra1, Ra2, Rb1 및 Rb2 는 각각 독립적으로 H 이고,
R1 및 R2 는 각각 독립적으로 C1-C4 알킬이고,
R5 내지 R7 은 각각 독립적으로 H 또는 C1-C4 알킬이고,
L1 은 -(CH2)m- 이고 {여기서, 상기 -(CH2)m- 의 하나 이상의 H 는 중수소로 치환될 수 있음},
L2 는 -(CH2)n- 또는
Figure 112020010691441-pat00108
이고 {여기서, 상기 -(CH2)n- 및
Figure 112020010691441-pat00109
의 하나 이상의 H 는 C1- C4 알킬로 치환될 수 있음},
m 은 1 이고,
n 은 0, 1 또는 2 이고,
p 는 2 인,
화학식 I 로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염.According to claim 1,
X is
Figure 112020010691441-pat00126
ego,
Y is C 1 -C 4 alkyl, NR 5 R 6 , OR 7 , C 4 -C 6 cycloalkyl, C 5 -C 10 spiro ring, C 5 -C 10 bicyclic ring, 4-6 membered heterocyclo Alkyl, aryl or heteroaryl, wherein at least one H of the aryl or heteroaryl is C 1 -C 4 alkyl, OR 7 , Can be substituted with halo or C 1 -C 4 haloalkyl},
Z is
Figure 112020010691441-pat00106
ego,
R a1 , R a2 , R b1 and R b2 are each independently H,
R 1 and R 2 Are each independently C 1 -C 4 alkyl,
R 5 to R 7 are each independently H or C 1 -C 4 alkyl,
L 1 is -(CH 2 ) m- (wherein at least one H of -(CH 2 ) m -can be substituted with deuterium),
L 2 is -(CH 2 ) n -or
Figure 112020010691441-pat00108
And {where, -(CH 2 ) n -and
Figure 112020010691441-pat00109
At least one H of may be substituted with C 1 -C 4 alkyl},
m is 1,
n is 0, 1 or 2,
p is 2,
A compound represented by the formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof. 제 2 항에 있어서,
X 는
Figure 112020010691441-pat00110
이고,
Y 는 C1-C4 알킬, NR5R6, OR7, C4-C6 시클로알킬, C5-C10 스파이로 고리, C5-C10 바이사이클릭 고리, 피페리디닐, 몰폴리닐, 테트라하이드로피라닐, 페닐, 나프탈레닐, 피리디닐 또는 퀴놀리닐이고 {여기서, 상기 페닐, 나프탈레닐, 피리디닐 또는 퀴놀리닐의 하나 이상의 H는 C1-C4 알킬, OR7, F, Cl, Br 또는 CF3로 치환될 수 있음},
Z 는
Figure 112020010691441-pat00121
이고,
R1 및 R2 는 각각 독립적으로 C1-C4 알킬이고,
R5 내지 R7 은 각각 독립적으로 H 또는 C1-C4 알킬이고,
L1 은 -(CH2)m- 이고 {여기서, 상기 -(CH2)m- 의 하나 이상의 H 는 중수소로 치환될 수 있음},
L2 는 -(CH2)n- 또는
Figure 112020010691441-pat00123
이고 {여기서, 상기 -(CH2)n- 및
Figure 112020010691441-pat00124
의 하나 이상의 H 는 C1-C4 알킬로 치환될 수 있음},
m 은 1 이고,
n 은 0, 1 또는 2 이고,
p 는 2 인,
화학식 I 로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염.According to claim 2,
X is
Figure 112020010691441-pat00110
ego,
Y is C 1 -C 4 alkyl, NR 5 R 6 , OR 7 , C 4 -C 6 cycloalkyl, C 5 -C 10 spiro ring, C 5 -C 10 bicyclic ring, piperidinyl, morphpoly Nil, tetrahydropyranyl, phenyl, naphthalenyl, pyridinyl or quinolinyl, wherein at least one H of the phenyl, naphthalenyl, pyridinyl or quinolinyl is C 1 -C 4 alkyl, OR 7 , Can be substituted with F, Cl, Br or CF 3 },
Z is
Figure 112020010691441-pat00121
ego,
R 1 and R 2 Are each independently C 1 -C 4 alkyl,
R 5 to R 7 are each independently H or C 1 -C 4 alkyl,
L 1 is -(CH 2 ) m- (wherein at least one H of -(CH 2 ) m -can be substituted with deuterium),
L 2 is -(CH 2 ) n -or
Figure 112020010691441-pat00123
And {where, -(CH 2 ) n -and
Figure 112020010691441-pat00124
At least one H of may be substituted with C 1 -C 4 alkyl},
m is 1,
n is 0, 1 or 2,
p is 2,
A compound represented by the formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof. 제 1 항에 있어서, 하기 화합물들로 이루어진 군으로부터 선택된 어느 하나인 화학식 I 로 표시되는 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염:
1) 3-(4'-((2-부틸-5-((3-(2-플루오로페닐)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
4) 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
5) 3-(4'-((2-부틸-5-((3-(메톡시메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
6) 3-(4'-((2-부틸-5-((3-(2-메톡시에틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-yl)-1,2,4-옥사다이아졸-5(4H)-온;
7) 3-(4'-((2-부틸-5-((3-이소프로필-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
8) 3-(4'-((2-부틸-5-((3-(다이메틸아미노)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
9) 3-(4'-((2-부틸-5-((3-((다이메틸아미노)메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
10) 3-(4'-((2-부틸-5-((3-(다이에틸아미노)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
11) 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
12) 3-(4'-((2-부틸-5-((3-(2-메톡시프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
13) 3-(4'-((2-부틸-4-이소프로필-5-((3-메틸-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
14) 3-(4'-((2-부틸-4-메틸-5-((3-메틸-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
15) 3-(4'-((5-((3-벤질-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
16) 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
17) 3-(4'-((5-((3-벤질-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
18) 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
20) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(스파이로[2.2]펜탄-1-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
21) 3-(4'-((2-부틸-5-((3-(이소프로폭시메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
23) 3-(4'-((2-부틸-5-((3-(3-클로로피리딘-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
24) 3-(4'-((2-부틸-5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
25) 3-(4'-((2-부틸-5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-이소프로필-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
26) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2-페닐프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
27) 3-(4'-((2-부틸-5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸-d2)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
28) 3-(4'-((2-부틸-5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸-d2)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
29) 3-(4'-((2-부틸-4-메틸-5-((3-(4-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
30) 3-(4'-((2-부틸-5-((3-(4-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
31) 3-(4'-((2-부틸-5-((3-(4-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
32) 3-(4'-((2-부틸-5-((3-(3-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
33) 3-(4'-((2-부틸-5-((3-(3,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
34) 3-(4'-((5-((3-터트-부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
35) 3-(4'-((5-((3-(4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
36) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(피페리딘-1-일메틸)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
37) 3-(4'-((4-메틸-5-((3-(4-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
38) 3-(4'-((5-((3-(4-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
39) 3-(4'-((5-((3-(4-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
40) 3-(4'-((5-((3-(3-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
41) 3-(4'-((5-((3-(3,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
42) 3-(4'-((5-((3-(2,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
43) 3-(4'-((5-((3-사이클로펜틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
44) 3-(4'-((5-((3-(사이클로펜틸메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
45) 3-(4'-((5-((3-(사이클로헥실메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
46) 3-(4'-((2-부틸-5-((3-(2,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
47) 3-(4'-((2-부틸-5-((3-(사이클로헥실메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-yl)-1,2,4-옥사다이아졸-5(4H)-온;
48) 3-(4'-((2-부틸-5-((3-(사이클로펜틸메틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
49) 3-(4'-((2-부틸-5-((3-사이클로펜틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
51) 3-(4'-((5-((3-(2-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
52) 3-(4'-((5-((3-(3,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
53) 3-(4'-((5-((3-(2,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
54) 3-(4'-((5-((3-(2-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
55) 3-(4'-((5-((3-(4-브로모벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
56) 3-(4'-((5-((3-(3-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
57) 3-(4'-((5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
58) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(2,4,6-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
59) 3-(4'-((4-메틸-6-옥소-5-((3-(피페리딘-1-일)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
60) 3-(4'-((5-((3-사이클로헥실-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
61) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
62) 3-(4'-((2-부틸-4-메틸-5-((3-(2-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
63) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(3-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
64) 3-(4'-((2-부틸-5-((3-(2,3-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
65) 3-(4'-((4-메틸-6-옥소-5-((3-(피페리딘-1-일메틸)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
66) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(3-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
67) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(4-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
69) 3-(4'-((4-메틸-5-((3-(몰폴리노메틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
70) 3-(4'-((4-메틸-6-옥소-5-((3-(1-페닐사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
71) 3-(4'-((2-부틸-5-((3-(2,5-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
72) 3-(4'-((2-부틸-5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
73) 3-(4'-((2-부틸-5-((3-(2-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
74) 3-(4'-((2-부틸-5-((3-(2,6-다이클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
75) 3-(4'-((4-메틸-5-((3-(2-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
76) 3-(4'-((5-((3-(2,3-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
77) 3-(4'-((5-((3-(2,6-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
78) 3-(4'-((5-((3-(3-클로로-5-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
79) 3-(4'-((5-((3-(4-브로모벤질)-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
80) 3-(4'-((2-부틸-5-((3-(3-클로로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
81) 3-(4'-((2-부틸-5-((3-(3,4-다이플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
82) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(4-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
84) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(1-페닐사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
85) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(2-(트리플루오로메틸)벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
87) 3-(4'-((5-((3-(2-클로로-4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
88) 3-(4'-((4-메틸-6-옥소-2-프로필-5-((3-(3,4,5-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
89) 3-(4'-((2-부틸-4-메틸-5-((3-(몰폴리노메틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
90) 3-(4'-((2-부틸-4-메틸-5-((3-(3-메틸벤질)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
91) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(2,4,6-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
92) 3-(4'-((2-부틸-5-((3-사이클로헥실-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
93) 3-(4'-((5-((3-(2-클로로-6-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
94) 3-(4'-((4-메틸-5-((3-(2-메틸펜탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸l)-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
95) 3-(4'-((2-부틸-5-((3-(3-클로로-5-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
97) 3-(4'-((2-부틸-5-((3-(2-클로로-6-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
98) 3-(4'-((2-부틸-5-((3-(2-클로로-4-플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
99) 3-(4'-((2-부틸-4-메틸-5-((3-(2-메틸펜탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
100) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(3,4,5-트리플루오로벤질)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
101) 3-(4'-((5-((3-(1-(2-클로로페닐)에틸)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소-2-프로필피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
102) 3-(4'-((2-부틸-5-((3-(2-사이클로헥실프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
103) 3-(4'-((2-부틸-5-((3-(2-(4-클로로-2-플루오로페닐)프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
104) 3-(4'-((2-부틸-5-((3-(2-(2-클로로-6-플루오로페닐)프로판-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
105) 3-(4'-((2-부틸-5-((3-(3-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
106) 3-(4'-((2-부틸-5-((3-(2-메톡시페닐)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
107) 3-(4'-((2-부틸-5-((3-(2-메톡시벤질)-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
108) 3-(4'-((2-부틸-4-메틸-5-((3-(나프탈렌-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
109) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(테트라하이드로-2H-피란-4-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
111) 3-(4'-((2-부틸-5-((3-사이클로부틸-1,2,4-옥사다이아졸-5-일)메틸)-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
112) 3-(4'-((5-((3-(바이사이클로[2.2.1]헵탄-2-일)-1,2,4-옥사다이아졸-5-일)메틸)-2-부틸-4-메틸-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
113) 3-(4'-((2-부틸-4-메틸-5-((3-(1-메틸사이클로부틸)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온;
114) 3-(4'-((2-부틸-4-메틸-5-((3-(나프탈렌-1-일)-1,2,4-옥사다이아졸-5-일)메틸)-6-옥소피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온; 및
115) 3-(4'-((2-부틸-4-메틸-6-옥소-5-((3-(퀴놀린-2-일)-1,2,4-옥사다이아졸-5-일)메틸)피리미딘-1(6H)-일)메틸)바이페닐-2-일)-1,2,4-옥사다이아졸-5(4H)-온.The compound according to claim 1, which is any one selected from the group consisting of the following compounds: an optical isomer thereof, or a pharmaceutically acceptable salt thereof:
1) 3-(4'-((2-butyl-5-((3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
4) 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyriimi Din-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
5) 3-(4'-((2-butyl-5-((3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
6) 3-(4'-((2-butyl-5-((3-(2-methoxyethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
7) 3-(4'-((2-butyl-5-((3-isopropyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
8) 3-(4'-((2-butyl-5-((3-(dimethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
9) 3-(4'-((2-butyl-5-((3-((dimethylamino)methyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
10) 3-(4'-((2-butyl-5-((3-(diethylamino)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
11) 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl-6-oxophy Rimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
12) 3-(4'-((2-butyl-5-((3-(2-methoxypropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
13) 3-(4'-((2-butyl-4-isopropyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
14) 3-(4'-((2-butyl-4-methyl-5-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6-oxopyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
15) 3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6-oxopyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
16) 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
17) 3-(4'-((5-((3-benzyl-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-isopropyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
18) 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
20) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(spyro[2.2]pentan-1-yl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
21) 3-(4'-((2-butyl-5-((3-(isopropoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
23) 3-(4'-((2-butyl-5-((3-(3-chloropyridin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
24) 3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
25) 3-(4'-((2-butyl-5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-isopropyl- 6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
26) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-phenylpropan-2-yl)-1,2,4-oxadiazole-5 -Yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
27) 3-(4'-((2-butyl-5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
28) 3-(4'-((2-butyl-5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl-d2)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
29) 3-(4'-((2-butyl-4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
30) 3-(4'-((2-butyl-5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
31) 3-(4'-((2-butyl-5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
32) 3-(4'-((2-butyl-5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
33) 3-(4'-((2-butyl-5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
34) 3-(4'-((5-((3-tert-butyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
35) 3-(4'-((5-((3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
36) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazole-5 -Yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
37) 3-(4'-((4-methyl-5-((3-(4-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
38) 3-(4'-((5-((3-(4-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
39) 3-(4'-((5-((3-(4-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
40) 3-(4'-((5-((3-(3-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
41) 3-(4'-((5-((3-(3,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
42) 3-(4'-((5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
43) 3-(4'-((5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
44) 3-(4'-((5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propyl Pyrimidine-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
45) 3-(4'-((5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propyl Pyrimidine-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
46) 3-(4'-((2-butyl-5-((3-(2,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
47) 3-(4'-((2-butyl-5-((3-(cyclohexylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
48) 3-(4'-((2-butyl-5-((3-(cyclopentylmethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-ox Sopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
49) 3-(4'-((2-butyl-5-((3-cyclopentyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
51) 3-(4'-((5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
52) 3-(4'-((5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
53) 3-(4'-((5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
54) 3-(4'-((5-((3-(2-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
55) 3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
56) 3-(4'-((5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
57) 3-(4'-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
58) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
59) 3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-yl)-1,2,4-oxadiazol-5-yl)methyl) -2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
60) 3-(4'-((5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxo-2-propylpyrimidine- 1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
61) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
62) 3-(4'-((2-butyl-4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
63) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
64) 3-(4'-((2-butyl-5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
65) 3-(4'-((4-methyl-6-oxo-5-((3-(piperidin-1-ylmethyl)-1,2,4-oxadiazol-5-yl)methyl )-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
66) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
67) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
69) 3-(4'-((4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
70) 3-(4'-((4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-2 -Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
71) 3-(4'-((2-butyl-5-((3-(2,5-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
72) 3-(4'-((2-butyl-5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
73) 3-(4'-((2-butyl-5-((3-(2-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
74) 3-(4'-((2-butyl-5-((3-(2,6-dichlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl -6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
75) 3-(4'-((4-methyl-5-((3-(2-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6-oxo-2- Propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
76) 3-(4'-((5-((3-(2,3-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
77) 3-(4'-((5-((3-(2,6-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
78) 3-(4'-((5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
79) 3-(4'-((5-((3-(4-bromobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-2-butyl-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
80) 3-(4'-((2-butyl-5-((3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
81) 3-(4'-((2-butyl-5-((3-(3,4-difluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4- Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
82) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(4-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
84) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(1-phenylcyclobutyl)-1,2,4-oxadiazol-5-yl) Methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
85) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(2-(trifluoromethyl)benzyl)-1,2,4-oxadiazole- 5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
87) 3-(4'-((5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
88) 3-(4'-((4-methyl-6-oxo-2-propyl-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
89) 3-(4'-((2-butyl-4-methyl-5-((3-(morpholinomethyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
90) 3-(4'-((2-butyl-4-methyl-5-((3-(3-methylbenzyl)-1,2,4-oxadiazol-5-yl)methyl)-6- Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
91) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(2,4,6-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
92) 3-(4'-((2-butyl-5-((3-cyclohexyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
93) 3-(4'-((5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
94) 3-(4'-((4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyll)-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
95) 3-(4'-((2-butyl-5-((3-(3-chloro-5-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
97) 3-(4'-((2-butyl-5-((3-(2-chloro-6-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
98) 3-(4'-((2-butyl-5-((3-(2-chloro-4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
99) 3-(4'-((2-butyl-4-methyl-5-((3-(2-methylpentan-2-yl)-1,2,4-oxadiazol-5-yl)methyl )-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
100) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(3,4,5-trifluorobenzyl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
101) 3-(4'-((5-((3-(1-(2-chlorophenyl)ethyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxo-2-propylpyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
102) 3-(4'-((2-butyl-5-((3-(2-cyclohexylpropan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-4 -Methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
103) 3-(4'-((2-butyl-5-((3-(2-(4-chloro-2-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole -5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H) -On;
104) 3-(4'-((2-butyl-5-((3-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole -5-yl)methyl)-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H) -On;
105) 3-(4'-((2-butyl-5-((3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
106) 3-(4'-((2-butyl-5-((3-(2-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
107) 3-(4'-((2-butyl-5-((3-(2-methoxybenzyl)-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
108) 3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
109) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(tetrahydro-2H-pyran-4-yl)-1,2,4-oxadiazole -5-yl)methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
111) 3-(4'-((2-butyl-5-((3-cyclobutyl-1,2,4-oxadiazol-5-yl)methyl)-4-methyl-6-oxopyrimidine -1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
112) 3-(4'-((5-((3-(bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-2- Butyl-4-methyl-6-oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
113) 3-(4'-((2-butyl-4-methyl-5-((3-(1-methylcyclobutyl)-1,2,4-oxadiazol-5-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one;
114) 3-(4'-((2-butyl-4-methyl-5-((3-(naphthalen-1-yl)-1,2,4-oxadiazol-5-yl)methyl)-6 -Oxopyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one; And
115) 3-(4'-((2-butyl-4-methyl-6-oxo-5-((3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl) Methyl)pyrimidin-1(6H)-yl)methyl)biphenyl-2-yl)-1,2,4-oxadiazole-5(4H)-one. 제 1 항 내지 제 4 항 중 어느 하나의 항의 화합물, 이의 광학 이성질체, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 고혈압 또는 당뇨병의 치료 또는 예방용 약학적 조성물.A pharmaceutical composition for the treatment or prevention of hypertension or diabetes, comprising the compound of any one of claims 1 to 4, an optical isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. 제 5 항에 있어서, 상기 고혈압은 본태성 고혈압인 약학적 조성물.The pharmaceutical composition according to claim 5, wherein the hypertension is essential hypertension. 제 5 항에 있어서, 상기 당뇨병은 제2형 당뇨병인 약학적 조성물.The pharmaceutical composition according to claim 5, wherein the diabetes is type 2 diabetes. 제 5 항에 있어서, 고혈압 및 당뇨병을 동시에 치료 또는 예방하기 위한 약학적 조성물.
The pharmaceutical composition according to claim 5, for the treatment or prevention of hypertension and diabetes simultaneously.
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