KR101502335B1 - Ｆａｂ Ｉ 저해제 및 그의 제조 방법 - Google Patents

Ｆａｂ Ｉ 저해제 및 그의 제조 방법 Download PDF

Info

Publication number
KR101502335B1
KR101502335B1 KR1020087011392A KR20087011392A KR101502335B1 KR 101502335 B1 KR101502335 B1 KR 101502335B1 KR 1020087011392 A KR1020087011392 A KR 1020087011392A KR 20087011392 A KR20087011392 A KR 20087011392A KR 101502335 B1 KR101502335 B1 KR 101502335B1
Authority
KR
South Korea
Prior art keywords
pyridin
benzyl
methyl
ethoxy
thiophen
Prior art date
Application number
KR1020087011392A
Other languages
English (en)
Other versions
KR20080068060A (ko
Inventor
김철민
현영란
신동규
노성구
조중명
Original Assignee
크리스탈지노믹스(주)
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 크리스탈지노믹스(주) filed Critical 크리스탈지노믹스(주)
Publication of KR20080068060A publication Critical patent/KR20080068060A/ko
Application granted granted Critical
Publication of KR101502335B1 publication Critical patent/KR101502335B1/ko

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/69—Two or more oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/14—Oxygen atoms
    • C07D237/16—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

Fab I 저해에 효과적인 화합물 및 박테리아 감염의 치료 방법을 제공한다.

Description

Ｆａｂ Ｉ 저해제 및 그의 제조 방법{Fab I INHIBITOR AND PROCESS FOR PREPARING SAME}
본 발명은 박테리아 지방산 생합성과 관련되어 있는 Fab I를 저해하는 신규 화합물에 관한 것이다. 본 출원은 2005년 10월 13일자로 출원된 "신규 Fab I 저해제 및 그의 제조 방법"이라는 명칭의 가출원 및 2006년 9월 26일자로 출원된 가출원 제60/827,029호에 대해 미국 특허법 35 U.S.C. 119(e) 하에 우선권을 주장하며, 상기 출원은 본원에 참고 통합되어 있다.
지방산 합성효소(fatty acid synthase, FAS)는 모든 생명체에서 포화 지방산의 전반적인 생합성 경로와 관련되어 있으나, FAS의 구조 조직은 생명체 사이에서 매우 다양하다. 척추동물과 효모의 FAS의 뚜렷한 특징은 모든 효소 활성이 하나 또는 두 개의 폴리펩타이드 체인에 암호화되어 있으며, 아실 운반 단백질(acyl carrier protein, ACP)이 하나의 복합체 형태로 존재한다는 점이다. 반면에, 박테리아 FAS의 경우, 각각의 합성 단계가 별개의 단일기능 효소에 의해 촉매되고, ACP는 따로 떨어진 별개의 단백질이다. 그러므로, 저해제를 사용하여 합성 단계 중 하나를 억제함으로써 박테리아 FAS를 선택적으로 억제하는 것이 가능하다.
NADH-의존 에노일-ACP 환원효소(Fab I)는 박테리아 지방산 생합성의 각 사이클과 관련된 네 가지 반응 단계에서 마지막 단계와 관련되어 있다(Payne et al., Drug Discovery Today 6, 2001, 537-544 참조). 첫 단계인 말로닐-ACP의 아세틸-CoA(Fab H)와의 축합은 β-케토아실-ACP 합성효소에 의해 촉매된다. 두 번째 단계는 NADPH-의존 β-케토아실-ACP 환원효소(Fab G)에 의한 케토에스터 환원이다. 이어서, β-하이드록시아실-ACP 디하이드레이즈(Fab A 또는 Fab Z)에 의한 탈수에 의해 트랜스-2-에노일-ACP로 된다. 마지막으로, 네 번째 단계에서는, 트랜스-2-에노일-ACP가 Fab I에 의해서 두 개의 탄소 원자를 더 갖는 아실-ACP로 전환된다. 이같은 사이클이 반복되어서, 결국에는 팔미토일-ACP(16C)가 되고, 팔미토일-ACP에 의한 Fab I의 저해로 인해 이 사이클이 멈추게 된다(Heath et al., J. Biol. Chem. 271, 1996, 1833-1836 참조). 따라서, Fab I는 박테리아 지방산 생합성의 전반적인 합성 경로의 생합성 효소이다.
최근의 연구에 의하면, Fab I는 트리클로산(McMurry et al., Nature, 1998, 394, 531-532 참조) 또는 다이아자보린(Baldock et al., Science, 1996, 274, 2107-2110 참조)과 같은 광범위한 스펙트럼의 항생제에 대한 표적임이 밝혀졌다. 또한, 다이아자보린은 Fab I와 공유결합체를 형성함으로써 Fab I의 비가역적 저해제로서 기능하는 반면(Baldock et al., Biochem. Pham. 1998, 55, 1541-1549 참조), 트리클로산은 Fab I의 가역적 저해제임이 밝혀졌다(Ward et al., Biochem. 38, 12514-12525 참조).
PCT 공개공보 제WO2001/027103호는 다음 화학식으로 표시되는 Fab I 저해제 또는 그의 약학적으로 허용가능한 염을 개시한다:
Figure 112008033761743-pct00001
상기 식에서,
Figure 112008033761743-pct00002
이고;
B는 H, C1-4 알킬 또는 C3-6 사이클로알킬이고;
C는
Figure 112008033761743-pct00003
Figure 112008033761743-pct00004
이고;
D는 H 또는 C1-4 알킬이고;
E는 상기 결합이 이중결합인 경우 CH2이거나; 상기 결합이 단일결합인 경우 H 또는 C1-4 알킬이고(여기서, A는 H 또는 C1 -4 알킬이다);
F는 H 또는 C1-4 알킬이고;
G는 H, C1-4 알킬 또는 C0-6 알킬아릴이고;
I는 O 또는 NR'2이고;
Q는 H, C1 -4 알킬, N(R')2, NHC(O)R', NHCH2C(O)R' 또는 NHC(O)CH=CHR'이고;
X는 각각 독립적으로 H, C1 -4 알킬, CH2OH, OR', SR', CN, N(R')2, CH2N(R')2, NO2, CF3, CO2R', CON(R')2, COR', F, Cl, Br, I 또는 -S(O)rCF3(r은 0, 1 또는 2이다)이고;
W는 S 또는 O이고;
M은 CH2 또는 O이고;
L은 CH2 또는 C(O)이고; 및
R'는 각각 독립적으로 H, C1 -4 알킬 또는 C0 -6 알킬아릴이다.
또한, PCT 공개공보 제WO2004/052890호 및 제WO2004/064837호 및 캐나다 특허 제2,444,957호는 박테리아 치료용 Fab I 저해제를 개시한다.
본 발명자들은 MRSA(methicillin resistant Staphylococcos Aureus)를 포함한 그람 양성균에 대한 광범위한 항균활성을 갖는 신규한 Fab I 저해제를 개발하였다.
발명의 요약
본 발명의 목적은 Fab I를 효과적으로 저해하고 박테리아 감염의 치료에 유용한 신규 화합물을 제공하는 것이다.
본 발명의 일태양에 따르면, 하기의 화학식 I 또는 II의 화합물 또는 염, 산, 에스터, 아마이드 및 나이트릴로 이루어진 그룹에서 선택된 이의 약학적으로 허용가능한 유사체를 제공한다:
Figure 112008033761743-pct00005
Figure 112008033761743-pct00006
상기 식에서,
R1은 하기로 이루어진 라디칼 그룹에서 선택되고: (a) H, (b) C1-8 알킬, C1-8 알케닐, C1-8 알키닐, (c) 아릴, C3-8 사이클로알킬, C3-8 사이클로알케닐,
(d) N, S 및 O에서 선택된 하나 이상의 헤테로원자를 함유하는 그룹 (c)의 라디칼의 유사체, 및
(e) 그룹 (b), (c) 및 (d)로 이루어진 그룹에서 선택된 라디칼의 치환된 유사체(여기서, 상기 치환된 유사체는 하기로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유한다:
하이드록실, 할로겐, C1-6 알킬, C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, 알킬옥시, 아미노, 알킬아미노, 카복실, 나이트로, 설포닐아마이드, 알킬설포닐, 아마이드, 다이옥소아이소인돌, 트라이할로알킬, 아릴, 헤테로아릴, 치환된 아릴, 및 치환된 헤테로아릴(여기서, 상기 치환된 아릴 및 치환된 헤테로아릴은 C1-6 알킬, C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, 알킬옥시, 아미노, 알킬아미노, 카복실, 나이트로, 설포닐아마이드, 알킬설포닐, 아마이드, 다이옥소아이소인돌, 트라이할로 알킬 및 아릴로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유한다));
A는 C-R2 및 N으로 이루어진 그룹에서 선택되고;
R2는 H, C1-5알킬, 벤질, 및 치환된 C1-5 알킬(여기서, 치환된 C1-5 알킬은 메틸, 에틸, 하이드록실, 하이드록실메틸 및 하이드록실에틸로 이루어진 그룹에서 선택된 하나 또는 그 이상의 치환기를 함유한다)로 이루어진 그룹에서 선택되고;
B는 카보닐, CH2 및 NH로 이루어진 그룹에서 선택되고;
R4는 하기로 이루어진 라디칼의 그룹에서 선택되고: (a) C1-8 알킬, C1-8 알케닐, C1-8 알키닐, (b) 아릴, C3-8 사이클로알킬, C3-8 사이클로알케닐, (c) N, S 및 O에서 선택된 하나 이상의 헤테로원자를 함유하는 그룹 (b)의 라디칼의 유사체, 및 (d) 그룹 (a), (b) 및 (c)로 이루어진 그룹에서 선택된 라디칼의 치환된 유사체(여기서, 상기 치환된 유사체는 하기로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유한다:
하이드록실, 할로겐, C1-6 알킬, C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, 알킬옥시, 아미노, 알킬아미노, 카복실, 나이트로, 설포닐아마이드, 알킬설포닐, 아마이드, 다이옥소아이소인돌, 트라이할로알킬, 아릴, 헤테로아릴, 치환된 아릴, 및 치환된 헤테로아릴(여기서, 상기 치환된 아릴 및 치환된 헤테로아릴은 C1-6 알킬, C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, 알킬옥시, 아미노, 알킬아미노, 카복실, 나이트로, 설포닐아마이드, 알킬설포닐, 아마이드, 다이옥소아이소인돌, 트라이할 로알킬, 및 아릴로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유한다));
W는 C-R6 및 N으로 이루어진 그룹에서 선택되고;
Z는 C-R5 및 N으로 이루어진 그룹에서 선택되고;
R5 및 R6은 각각 독립적으로 H, 할로겐, C1-5 알킬, 및 치환된 C1-5 알킬(여기서, 치환된 C1-5 알킬은 메틸, 에틸, 하이드록실, 하이드록실메틸 및 하이드록실에틸로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유한다)로 이루어진 그룹에서 선택되고; 및
X는 C, N, O 및 S에서 선택된다.
발명의 상세한 설명
본 발명의 일태양에 따르면, 화학식 I 또는 II의 신규 화합물 또는 그의 약학적으로 허용가능한 염을 제공한다.
본원에서 사용된 "헤테로아릴"이라는 용어는 고리 구조에서 N, S 또는 O로부터 선택된 하나 이상의 헤테로원자를 함유하는 아릴기를 의미한다. 예를 들어, 헤테로아릴에는 피롤, 피라졸, 이미다졸, 1,2,3-트라이아졸, 1,2,4-트라이아졸, 퓨란, 아이속사졸, 옥사졸, 싸이오펜, 아이소싸이아졸, 싸이아졸리딘, 싸이아졸, 1,2,5-옥사다이아졸, 1,2,3-옥사다이아졸, 1,2,5-싸이오다이아졸, 1,2,3-싸이오다이아졸, 1,3,4-옥사다이아졸, 1,3,4-싸이오다이아졸, 피리딘, 피리미딘, 테트라졸 및 트라이아진으로부터 유도된 것이 포함된다.
본원에서 사용된 "박테리아 관련 질병"이라는 용어는 박테리아 감염에 의해 발생하는 병 또는 질환을 의미하는데, Fab I 저해제 처리에 의해 경감되거나 완화될 수 있고, 이에 한정되는 것은 아니지만, 요로, 호흡 또는 피부 조직 감염, 패혈증 등을 포함할 수 있다.
본 발명의 화합물은 R 또는 S 배위의 비대칭 중심을 가질 수 있고, 따라서 본 발명은 화학식 I 또는 II의 화합물의 기하이성질체, 입체이성질체 및 라세미 혼합물을 포함하는 것으로 이해되어져야 한다.
비독성 부가염일 수 있는 본 발명의 화합물의 약학적으로 허용가능한 염은 산이나 염기를 사용하여 제조될 수 있다. 본 발명에서 사용될 수 있는 산의 예에는 염산, 브롬산, 인산 및 황산과 같은 무기산; 및 예컨대, 아세트산, 트라이플루오로아세트산, 시트르산, 포름산, 말레산, 옥살산, 숙신산, 벤조산, 타르타르산, 퓨마르산, 만델산, 아스코르브산 및 말산과 같은 유기 카복실산, 메탄설폰산 및 p-톨루엔설폰산과 같은 유기산이 포함된다. 본 발명에서 사용될 수 있는 염기의 예로는 알칼리금속 수산화물(예컨대, 수산화나트륨 및 수산화칼륨)과 같은 무기 염기, 알칼리금속 중탄산염(예컨대, 중탄산나트륨 및 중탄산칼륨), 알칼리금속 탄산염(예컨대, 탄산나트륨, 탄산칼륨 및 탄산칼슘) 및 아민과 같은 유기 염기가 포함된다.
또한, 본 발명의 화합물은 적당한 에스터 또는 아마이드 그룹을 갖는 약학적으로 허용가능한 유도체 또는 전구약물의 형태로 사용될 수 있다. 생체 내에서 화학적 또는 생화학적으로 가수분해될 수 있는 상기 에스터의 바람직한 예에는 인다 닐, 프탈리딜, 피발로일옥시메틸, 글라이실옥시메틸, 페닐글라이실옥시메틸 및 5-메틸-2-옥소-1,3-다이옥소렌-4-일메틸 에스터가 포함된다.
본 발명의 바람직한 화합물은 다음과 같다:
4-벤질옥시-1-(2-클로로-벤질)-1H-피리딘-2-온;
4-벤질옥시-1-(4-클로로-벤질)-1H-피리딘-2-온;
4-벤질옥시-1-(4-나이트로-벤질)-1H-피리딘-2-온;
4-벤질옥시-1-(2,5-다이클로로-벤질)-1H-피리딘-2-온;
4-벤질옥시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
4-벤질옥시-2-(4-메톡시-벤질옥시)-피리딘;
4-벤질옥시-1-(4-메톡시-벤질)-1H-피리딘-2-온;
4-벤질옥시-2-(4-메틸-벤질옥시)-피리딘;
4-벤질옥시-1-(4-메틸-벤질)-1H-피리딘-2-온;
4-벤질옥시-1-(6-클로로-피리딘-3-일메틸)-1H-피리딘-2-온;
4-벤질옥시-1-(3-클로로-벤질)-1H-피리딘-2-온;
1-벤질-4-벤질옥시-1H-피리딘-2-온;
1-(4-아미노-벤질)-4-벤질옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-하이드록시-1H-피리딘-2-온;
3-벤질-1-(2,4-다이클로로-벤질)-4-하이드록시-1H-피리딘-2-온;
4-(바이페닐-4-일메톡시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(2,4-다이클로로-벤질옥시)-1H-피리딘-2-온;
4-(2-클로로-벤질옥시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-메톡시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-아이소프로폭시-1H-피리딘-2-온;
4-사이클로헥실메톡시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-프로폭시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-아이소부톡시-1H-피리딘-2-온;
4-부톡시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-옥틸옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(4-메틸-펜톡시)-1H-피리딘-2-온;
4-(부트-3-에닐옥시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
[1-(2,4-다이클로로-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시]-아세트산 에틸에스터;
1-(2,4-다이클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온;
1-벤질-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
4-펜틸옥시-1-프로필-1H-피리딘-2-온;
1-부틸-4-펜틸옥시-1H-피리딘-2-온;
1-아이소부틸-4-펜틸옥시-1H-피리딘-2-온;
1-(3-메틸-부틸)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-헥실옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-헵틸옥시-1H-피리딘-2-온;
1-(4-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
4-아릴옥시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(3-메톡시-프로폭시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(3-에틸아미노-프로폭시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(2-에톡시-에톡시)-1H-피리딘-2-온;
1-(3-메틸-부트-2-에닐)-4-펜틸옥시-1H-피리딘-2-온;
4-펜틸옥시-1-싸이아졸-4-일메틸-1H-피리딘-2-온;
4-펜틸옥시-1-피리딘-3-일메틸-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(4-메틸-펜트-3-에닐옥시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(3-메톡시-프로폭시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-페네틸옥시-1H-피리딘-2-온;
1-(2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
4-펜틸-1-페네틸-1H-피리딘-2-온;
1-(2,4-다이클로로-5-플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(3,4-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(3,4-다이플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
4-(4-벤질옥시-부톡시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(4-하이드록시-부톡시)-1H-피리딘-2-온;
4-(5-벤질옥시-펜틸옥시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(5-하이드록시-펜틸옥시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(2-메틸-벤질옥시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(4-메틸-벤질옥시)-1H-피리딘-2-온;
1-(2-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온;
N-[2-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드;
4-펜틸옥시-1-(2-트라이플루오로메틸-벤질)-1H-피리딘-2-온;
N-[4-(4-벤질옥시-2-옥소-2H-피리딘-1-일메틸)-페닐]아세트아마이드;
1-(2,4-다이클로로-벤질)-4-(나프탈렌-2-일메톡시)-1H-피리딘-2-온;
1-나프탈렌-2-일메틸-4-펜틸옥시-1H-피리딘-2-온;
4-벤질옥시-1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(3-메틸-부톡시)-1H-피리딘-2-온;
1-(2-메틸-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온;
4-(3-메틸-부톡시)-1-(2-나이트로-벤질)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-펜틸아미노-1H-피리딘-2-온;
1-(2,3-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,3-다이메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
4-(5-벤질옥시-펜틸옥시)-1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-1H-피리딘-2-온;
1-(2-클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온;
1-(3,4-다이클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온;
1-(2,4-다이클로로-5-플루오로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온;
1-벤질-4-(3-메틸-부톡시)-1H-피리딘-2-온;
1-(4-클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-펜틸옥시-1H-피리미딘-2-온;
1-(2,4-다이클로로-벤질)-4-(4-메틸-펜틸옥시)-1H-피리미딘-2-온;
1-(2,4-다이클로로-벤질)-4-페녹시-1H-피리미딘-2-온;
4-(부틸-메틸-아미노)-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온;
1-(2,4-다이클로로-벤질)-4-(2-다이에틸아미노-에톡시)-1H-피리미딘-2-온;
4-부톡시-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온;
1-(2,6-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-6-플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-메틸-3-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(4-메톡시-3,5-다이메틸-피리딘-2-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(5-하이드록시-펜틸옥시)-1H-피리딘- 2-온;
1-(2-메톡시-5-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(5-아미노-2-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-에틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-5-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(5-아미노-2-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(4-메톡시-2,3-다이메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-메틸-피리딘-3-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
N-[4-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드;
1-(2,4-다이클로로-벤질)-4-(3-다이메틸아미노-프로폭시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(4-다이메틸아미노-부톡시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(6-다이메틸아미노-헥실옥시)-1H-피리미딘-2-온;
1-(2,4-다이메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-5-트라이플루오로메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-하이드록시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
4-(3-사이클로-프로폭시)-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온;
1-(2,4-다이클로로-벤질)-4-(3-메틸-펜틸옥시)-1H-피리미딘-2-온;
1-(2,4-다이클로로-벤질)-4-헥스-4-에닐옥시-1H-피리미딘-2-온;
4-(2-사이클로프로필-에톡시)-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온;
1-(2,4-다이클로로-벤질)-4-(3-메틸-펜틸옥시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(5-모폴린-4-일-펜틸옥시)-1H-피리딘-2-온;
1-(2-클로로-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-5-에톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-5-프로폭시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-[2-클로로-5-(2-하이드록시-에톡시)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
[4-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-옥시]-아세토나이트릴;
1-[5-(2-아미노-에톡시)-2-클로로-벤질]-4-펜틸옥시-1H-피리딘-2-온;
N-[2-메틸-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드;
1-(2-메틸-3-메틸아미노-벤질)-4-페닐옥시-1H-피리딘-2-온;
1-(3-다이메틸아미노-2-메틸-벤질)-4-페닐옥시-1H-피리딘-2-온;
1-(3-에틸아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(3-다이에틸아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-메틸-3-프로필아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(3-다이프로필아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-[3-(2-하이드록시-에틸아미노)-2-메틸-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-5-메톡시-4-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(4-아미노-2-클로로-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
N-[5-클로로-2-메톡시-4-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드;
1-(2-클로로-5-메톡시-4-메틸아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-4-다이메틸아미노-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-4-에틸아미노-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-5-메톡시-4-프로필아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-[2-클로로-4-(2-하이드록시-에틸아미노)-5-메톡시-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-(4-아미노-6-클로로-3-메톡시-2-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,4-다이아미노-6-클로로-3-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,5-다이클로로-6-메톡시-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤젠설포닐)-4-펜틸옥시-1H-피리딘-2-온;
1-(4-메탄설포닐-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(4-아미노-2-클로로-5-하이드록시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
4-(4-브로모-부톡시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온;
4-[1-(2,4-다이클로로-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시]-부틸암모늄;
1-(5-클로로-2,6-다이메톡시-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-아미노-5-클로로-6-메톡시-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
1-(6-아미노-2,5-다이클로로-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
5-클로로-6-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-3H-벤즈옥사졸-2-온;
1-(2-클로로-4-하이드록시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-4-아이소프로폭시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
2-[3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-프로필]-아이소인돌-1,3-다이온;
1-(3-아미노-프로필)-4-펜틸옥시-1H-피리딘-2-온;
N-[3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-프로필]-아세트아마이드;
1-(3-다이메틸아미노-프로필)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-6-메틸-4-펜틸옥시-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-6-메틸-3-펜틸-4-펜틸옥시-1H-피리딘-2-온;
1-(2-아미노-에틸)-4-펜틸옥시-1H-피리딘-2-온;
N-[2-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-에틸]-아세트아마이드;
N-[1,1-다이메틸-2-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-에틸]-메탄설폰아마이드;
N-[1-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-프로필]-메탄설폰아마이드;
1-(7-나이트로-벤조[1,3]다이옥솔-5-일메틸)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-3-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(3-아미노-2-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
N-[2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드;
N-[2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-메탄설폰아마이드;
N,N'-[2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-다이메탄설폰아마이드;
1-[2-클로로-3-(2-하이드록시-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
4-클로로-2-(2-클로로-벤질)-5-펜틸옥시-2H-피리다진-3-온;
2-(2-클로로-벤질)-5-펜틸옥시-2H-피리다진-3-온;
1-(3-아미노-2,6-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(3-벤질옥시-2-클로로-4-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-3,4-다이메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-3-하이드록시-4-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-[2-클로로-4-메톡시-3-(2-메톡시-에톡시)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-[2-클로로-4-메톡시-3-(2-피롤리딘-1-일-에톡시)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-[2-클로로-3-(2-다이메틸아미노-에톡시)-4-메톡시-벤질]-4-펜틸옥시-1H-피리딘-2-온;
2-{3-[2-클로로-6-메톡시-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페녹실]-프로필}-아이소인돌-1,3-다이온;
1-[3-(2-다이메틸아미노-에톡시)-2-메틸-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-[2-클로로-3-(2-다이메틸아미노-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-[2,6-다이클로로-3-(2-하이드록시-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-[2,6-다이클로로-3-(2-다이메틸아미노-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-[2,6-다이클로로-3-(3-하이드록시-프로필아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-[2,6-다이클로로-3-(3-다이메틸아미노-프로필아미노)-벤질]-4-펜틸옥시-1H-피리 딘-2-온;
1-[3-(3-아미노-프로필아미노)-2,6-다이클로로-벤질]-4-펜틸옥시-1H-피리딘-2-온;
1-(3-플루오로-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2-클로로-3-다이메틸아미노메틸-4-플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,6-다이클로로-3-메틸아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온;
1-(2,6-다이클로로-3-다이메틸아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온;
[2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐아미노]-아세트산;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(피리딘-4-일메톡시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(6-클로로-피리딘-3-일메톡시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(4-메톡시-3,5-다이메틸피리딘-2-일메톡시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-메틸-피리딘-3-일메톡시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(싸이아졸-4-일메톡시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(피리딘-2-일메톡시)-1H-피리딘-2-온;
펜탄산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘-4-일 에스터;
헥산산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘 -4-일 에스터;
1-(2-클로로-3-트라이플루오로메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온;
싸이오펜-2-카복실산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘-4-일 에스터;
톨루엔-4-설폰산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘-4-일 에스터;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(4,4,5,5,5-펜타플루오로-펜틸옥시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-다이메틸아미노-에톡시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(5-플루오로-펜틸옥시)-1H-피리딘-2-온;
3-[1-(2,4-다이클로로-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시메틸]-인돌-1-카복실산 테트라-부틸 에스터;
1-(2,4-다이클로로-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(2-싸이오펜-3-일-에톡시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-(3-피롤-1-일-프로폭시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(4-메틸-싸이아졸-5-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-(2-(5-브로모싸이오펜-2-일)-에톡시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-(2-(5-플루오로싸이오펜-2-일)-에톡시)-1H-피리딘-2-온;
1-[3-(2-하이드록시-에틸아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-아세트아마이드;
1-[3-(사이클로프로필메틸-아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
N-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-아세토나이트릴;
N-(2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-에틸)-아세트아마이드;
1-[2-메틸-3-(2-피롤-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-[2-메틸-3-(2-옥소-2-피롤리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-[2-메틸-3-(2-옥소-2-피페리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
N,N-다이메틸-2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메 틸]-페닐아미노}-아세트아마이드;
1-{2-메틸-3-[2-(4-메틸-피페라진-1-일)-2-옥소-에틸아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-[2-메틸-3-(2-모폴린-4-일-2-옥소-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-(2-퓨란-2-일-에톡시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(5-클로로-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(2,4-다이클로로-벤질)-4-[2-(3-메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-(2-벤조[b]싸이오펜-3-일-에톡시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(5-클로로-3-메틸-벤조[b]싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(3-메틸-벤조[b]싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸-퓨란-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(5-에틸-퓨란-2-일)-에톡시]-1H-피리딘-2-온;
5-[1-(3-아미노-2-메틸-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시메틸]-퓨란-2-카복실산 에틸 에스터;
1-[3-(2-다이메틸아미노-에틸아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)- 1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸설파닐-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-(2-벤조퓨란-2-일-에톡시)-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(3-메틸-아이속사졸-5-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(4,5-다이메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2-메틸-벤질)-4-[2-(5-에틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(3-아미노-2,6-다이클로로-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
N-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐}-아세트아마이드;
1-[2-메틸-3-(2-피페리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-[2-메틸-3-(2-모폴린-4-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
N-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐}-메탄설폰아마이드;
1-(3-아미노-2-메틸-벤질)-4-[2-(4-브로모-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온;
1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-[2-메틸-3-(2-피롤리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
N-(2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-에틸)-아세트아마이드;
1-{2-메틸-3-[(피리딘-3-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐 에스터;
1-{2-메틸-3-[(피리딘-4-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-{2-메틸-3-[(싸이아졸-4-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-[3-(4-메톡시-벤질옥시)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-{3-[(3,5-다이메틸-아이속사졸-4-일메틸)-아미노]-2-메틸-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-(3-하이드록시-2-메틸-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-{2-메틸-3-[(1-메틸-피롤리딘-2-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
1-{2-메틸-3-[2-(1-메틸-피롤리딘-2-일)-에틸아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
(2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-에틸)-포스폰산 다이에틸 에스터;
4-(아이소부틸싸이오)-1-(2-메틸-3-나이트로벤질)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(아이소부틸싸이오)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(퓨란-2-일메틸싸이오)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(펜틸싸이오)피리딘-2-(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(페네틸싸이오)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(부틸싸이오)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(싸이오펜-2-일메틸싸이오)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(펜틸싸이오)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(프로필싸이오)피리딘-2(1H)-온;
1-(3-아미노-2-메틸벤질)-4-(1-메틸부틸싸이오)피리딘-2(1H)-온;
N,N-다이메틸-3-(2-메틸-3-((2-옥소-4-(2-(싸이오펜-2-일)에톡시)피리딘-1(2H)-일)메틸)페닐아미노)프로판-1-설폰아마이드;
1-(3-아미노-2-메틸벤질)-4-(2-(싸이오펜-2-일)에틸아미노)피리딘-2-(1H)-온.
화학식 I 또는 II의 화합물은 피리다진 유도체, 피리미디논 유도체, 트라이아지논 유도체 또는 피리돈 유도체를 사용하여 간단한 알킬화 또는 아릴화로 제조될 수 있다.
화학식 I의 화합물의 바람직한 예는 반응식 1 또는 2에 나타난 바와 같이 제조될 수 있는 피리돈 화합물이다. 본원에서 사용된 바와 같이, NaH는 소듐 하이드라이드이고, TsCl은 p-톨루엔설포닐 클로라이드이고, Ac2O는 무수아세트산이고, BuOH는 부탄올이고, t-BuOH는 t-부탄올이고, Pd/C는 팔라듐/탄소이고, KOtBu는 포타슘 t-부톡사이드이고, Zn은 아연 분말이다.
반응식 1
Figure 112008033761743-pct00007
시약: (a) NaH, 벤질옥시프로필 브로마이드, DMF; (b) Pd/C, H 2 , MeOH; (c) TsCl, TEA, DCM; (d) 사이클로프로필아민, MeOH
반응식 2
Figure 112008033761743-pct00008
시약: (a) NaH, 2-메틸-3-나이트로벤질 클로라이드, DMF; (b) 하이드라진, Zn, EtOH; (c) 무수아세트산, TEA, DCM
상기에서 출발물질로 사용된 피리돈 유도체는 반응식 3 또는 4에서 각각 나타난 바와 같이 제조될 수 있다.
반응식 3
Figure 112008033761743-pct00009
시약: (a) BnCl, NaH, DMF; (b) Pd/C, H 2 , MeOH
반응식 4
Figure 112008033761743-pct00010
시약: (a) BuOH, KOtBu, t-BuOH; (b) Ac 2 O, 환류
화학식 I의 화합물의 또다른 바람직한 예는 메틸기로 치환되는 피리돈 화합물이고, 이는 반응식 5에 나타난 바와 같이 제조될 수 있다.
반응식 5
Figure 112008033761743-pct00011
시약: (a) NaH, 펜틸 브로마이드, DMF; (b) 벤질 아민, EtOH, 환류
화학식의 화합물의 또다른 바람직한 예는 피리다진 화합물이고, 반응식 6에 나타난 바와 같이 제조될 수 있다.
반응식 6
Figure 112008033761743-pct00012
시약: (a) NaH, 펜탄올, DMF; (b) 2,4-다이클로로벤질 클로라이드, NaH, DMF; (c) pd/C, H 2 , MeOH
반응식 6에서 펜탄올 대신 4-메틸펜탄올을 사용하면 2-(2,4-다이클로로벤질)-5-4-메틸펜틸옥시)피리다진-3(2H)-온이 생성된다:
Figure 112008033761743-pct00013
2-(2,4-다이클로로벤질)-5-(4-메틸펜틸옥시)피리다진-3(2H)-온
화학식 I 또는 II의 화합물은 Fab I의 활성을 효과적으로 저해한다. 따라서, 본 발명은 혈액, 오줌 및 림프와 같은 체액을 화학식 I 또는 II의 화합물과 접촉하도록 하는 것을 포함하는, Fab I의 활성을 저해하는 방법을 제공한다.
또한, 본 발명은 활성 성분으로서 화학식 I 또는 II의 화합물을 박테리아 관련 질병을 치료하고 예방하는 데 효과적인 양으로 포함하는 약학 조성물을 제공한다.
본 발명의 약학 조성물은 약학적으로 허용가능한 담체, 희석제, 보조제 또는 비히클를 포함할 수 있다. 담체, 희석제, 보조제 및 비히클의 예에는, 이에 한정된 것은 아니지만, 이온 교환제, 알루미나, 알루미늄 스테아레이트, 레시틴, 혈청 단백질, 예를 들면, 사람 혈청 단백질, 완충 물질, 예를 들면 인산염, 글리신, 소르브산, 칼륨 소르베이트, 포화 식물지방산의 부분 글리세라이드 혼합물, 물, 염 또는 전해질, 예를 들면, 프로타민 설페이트, 인산수소 이나트륨, 인산수소 칼륨, 염화나트륨 또는 아연 염, 콜로이드성 실리카, 마그네슘 트라이실리케이트, 폴리비닐 피롤리돈, 셀룰로스계 물질, 폴리에틸렌 글리콜, 소듐 카복시 메틸셀룰로스, 폴리아크릴레이트, 왁스, 폴리에틸렌-폴리옥시프로필렌-블록 중합체, 폴리에틸렌 글리콜, 양모지, 파라벤, 클로로부탄올, 페놀, 소르브산, 알루미늄 모노스테아레이트, 젤라틴 등이 포함된다. 또한, 등장화제, 예를 들면 당, 소듐 클로라이드 등이 포함되는 것이 바람직하다. 본 발명의 다양한 제형은 계면활성제, 가령 트윈(TWEEN™) 또는 스판(SPAN™), 유화제, 증량제 등을 사용하여 제조될 수 있고, 경구, 설하, 비경구, 흡입분무, 국소, 직장, 비내, 볼내, 질내 또는 이식된 저장기를 통하여 투여될 수 있다. 본원에서 사용된 "비경구"라는 용어는 피하, 정맥내, 근육내, 관절내, 활액낭내, 흉골내, 포막내, 간내, 병변내 및 두개내 주사 또는 주입 기술을 포함한다. 바람직하게는, 조성물은 경구, 복강내, 피하, 근육내 또는 정맥내 투여된다.
멸균성 주입가능한 제형은 수성 또는 유성 서스펜션의 형태일 수 있다. 이 서스펜션은 적당한 분산제 또는 습윤제 및 현탁제, 가령 물, 에탄올, 폴리올(프로필렌글리콜, 폴리에틸렌글리콜, 글리세롤 등), 그들의 적당한 혼합물, 식물성 오일(가령 올리브 오일), 및 주입가능한 유기 에스터, 가령 에틸 올레이트를 사용하여 통상적인 방법으로 제형화될 수 있다. 적당한 유동성은 예를 들면, 레시틴과 같은 코팅제의 사용에 의해, 분산시 요구되는 입자 크기의 유지에 의해, 그리고 계면활성제의 사용에 의해 유지될 수 있다.
경구 투여에 적당한 제형은 캡슐, 정제, 환제, 분말, 또는 과립의 형태일 수 있다. 그러한 고체 투여 형태에서, 상기 활성 화합물은 소듐 시트레이트 또는 다이칼슘 포스페이트와 같은 하나 이상의 불활성 운반체와 함께; 또는 충진제, 증량제, 결합제, 보습제, 칼슘 카보네이트 또는 특정 복합 실리케이트와 같은 붕해제, 파라핀과 같은 용액 지연제, 4급 암모늄 화합물과 같은 흡수 촉진제, 세틸 알코올 또는 글리세롤 모노스테아레이트와 같은 습윤제, 흡착제, 및 마그네슘 스테아레이트와 같은 윤활제, 고체 폴리에틸렌 글리콜 등, 또는 그들의 혼합물과 함께 혼합될 수 있다. 캡슐의 형태에서, 상기 활성 화합물은 완충제와 함께 혼합될 수 있고, 부형제, 가령, 락토스 또는 유당뿐만 아니라 고분자량 폴리에틸렌글리콜 등과 함께 혼합될 수 있다. 또한, 경구 투여에 적당한 제형은 수성 서스펜션, 용액, 시럽 등의 형태일 수 있다. 경구용으로 수성 서스펜션이 필요한 경우에, 상기 활성 성분은 유화제 및 현탁제와 결합된다. 필요하다면, 특정 감미제, 향미제 또는 착색 제도 첨가될 수 있다.
경구 투여를 위한 제형은 코팅제를 포함할 수 있고, 소화관의 특정 부분에서 상기 활성 화합물을 방출하기 위해서 특정 제제와 함께 제형화될 수 있다.
국소 투여를 위한 제형은 치료의 표적이 국소 적용을 통해서 쉽게 접근 가능한 부위 또는 기관, 예컨대, 눈, 피부 또는 하부 창자를 포함한다는 점에서 유용할 수 있다. 또한 국소-경피 패치도 국소 투여에 사용될 수 있다.
피부 또는 하부 창자에의 국소 적용을 위해서, 상기 조성물은 하나 이상의 적당한 담체에 현탁되거나 용해된 상기 활성 성분을 함유하는 연고, 로션, 크림 또는 스프레이의 형태로 제형화될 수 있다. 연고는 미네랄 오일, 액체 페트롤라툼, 백색 페트롤라툼, 프로필렌 글리콜, 폴리옥시에틸렌, 폴리옥시프로필렌, 유화 왁스 또는 물을 적당한 담체로서 함유할 수 있다. 로션, 크림 또는 스프레이는 미네랄 오일, 소르비탄 모노스테아레이트, 폴리소르베이트 60, 세틸 에스터 왁스, 세테아릴 알코올, 2-옥틸도데카놀, 벤질 알코올 또는 물을 적당한 담체로서 함유할 수 있다.
안과용으로, 상기 조성물은 벤질알코늄 클로라이드와 같은 보존제와 함께 또는 보존제 없이 등장의 pH 조정된 멸균 식염수에서 미소화된 서스펜션 또는 용액으로서 제형화될 수 있다. 또는, 상기 조성물은 페트롤라툼과 같은 안과용 연고로 제형화될 수 있다.
코 에어로졸 또는 흡입에 의한 투여에 적당한 제형은 식염수 중 용액의 형태일 수 있다. 상기 용액은 벤질 알코올 또는 기타 적당한 보존제, 생체이용율을 증 진시키기 위한 흡수 프로모터, 플루오로카본, 및/또는 기타 통상적인 가용화제 또는 분산제를 함유할 수 있다.
직장 또는 질 투여에 적당한 제형은 본 발명의 화합물을 체온에서 녹는 적당한 비자극적 부형제 또는 담체, 가령, 좌약 왁스, 코코아 버터, 또는 폴리에틸렌글리콜과 함께 혼합함으로써 제형화될 수 있다. 필요하다면, 본 발명의 화합물은 기타 항균제, 가령, 페니실린 또는 세팔로스포린과 함께 사용될 수 있다.
화학식 I 또는 II의 화합물의 1회 투여량은 약 50 내지 1,500mg의 범위일 수 있지만, 상기 투여량은 환자의 나이, 체중 및 증상에 따라 달라질 수 있다. 화학식 I 또는 II의 화합물의 일반적인 1일 투여량은 성인의 경우 약 50 내지 5,000mg, 또는 약 150 내지 3,000mg일 수 있고, 약 50 내지 2,000mg, 또는 약 100 내지 2,000mg, 또는 약 300 내지 2,500mg, 또는 약 500 내지 4,000mg, 또는 약 500 내지 5,000mg일 수 있다.
또한, 본 발명은 박테리아 관련 질병의 치료가 필요한 환자에게 유효량의 화학식 I 또는 II의 화합물을 투여하는 것을 포함하는, 박테리아 관련 질병의 치료 방법을 제공한다. 상기 방법으로 치료하는 환자는 사람 또는 사람이 아닌 포유류를 포함할 수 있다.
본 발명을 실시예에 대한 참조와 함께 더욱 상세히 설명한다. 그러나, 본 발명은 특정 실시예에 한정되는 것은 아니다.
제조예 1: 4-펜틸옥시-1H-피리딘-2-온의 합성
tert-부탄올 용매 중의 펜탄올(2.7g, 31mmol) 및 tert-부톡사이드(3.5g, 31mmol)의 용액을 상온에서 1시간 동안 교반한 후, 4-나이트로피리딘-N-옥사이드(4g, 28.6mmol)를 첨가하였다. 반응이 완료되면, 생성 용액을 에틸 아세테이트 및 물로 처리하고 분리하여, 유기 용매를 완전히 건조시켰다. 여기에 톨루엔을 첨가한 후, 감압 하에서 용매를 제거하였다. 남은 혼합물에 무수아세트산(40ml)을 첨가하고 3시간 동안 환류하였다. 무수아세트산를 완전히 건조시킨 후, MeOH(20ml) 및 3N NaOH(5ml)를 첨가하여 1시간 동안 교반하였다. MeOH를 적당히 건조시킨 후, 남은 혼합물을 6N HCl을 사용하여 중화시켰다. 생성 용액을 에틸 아세테이트(80ml)로 추출하고 실리카 겔 컬럼 크로마토그래피(에틸 아세테이트/MeOH, 10:1)에 가하여 표제 화합물(2.3g, 56%)을 수득하였다.
1H NMR (CDCl3, 300 MHz) δ 0.93 (t, 3H), 1.33-1.44 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.91-6.08 (m, 2H), 7.40 (d, 1H)
실시예 1: 4-벤질옥시-1-(2-클로로-벤질)-1H-피리딘-2-온
DMF 용매 중의 4-벤질옥시-1H-피리돈(300mg, 1.49mmol) 및 NaH(60mg, 1.49mmol) 용액을 30분 동안 교반하고 2-클로로벤질 클로라이드(240mg, 1.49mmol)를 첨가한 후, 상온에서 30분 동안 더 교반하였다. 생성 용액을 물 및 다이클로로메탄을 이용하여 처리하고 컬럼 크로마토그래피(에틸 아세테이트/헥산, 1:1)에 가 하여 정제하여 표제 화합물(320mg, 67%)을 수득하였다.
1H NMR (CDCl3, 300 MHz)■δ 5.00 (s, 2H), 5.20 (s, 2H), 5.97 (dd, 1H), 6.04 (d, 1H), 7.17-7.39 (m, 10H)
실시예 2 내지 13: 출발 물질을 제외하고는 실시예 1의 과정을 반복하여 표제 화합물을 수득하였다.
실시예 2: 4-벤질옥시-1-(4-클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.96 (s, 2H), 5.01 (s, 2H), 5.93 (dd, 1H), 5.99 (d, 1H), 7.09 (d, 1H), 7.19 (d, 2H), 7.24 (d, 2H), 7.28-7.36 (m, 5H)
실시예 3: 4-벤질옥시-1-(4-나이트로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 5.08 (s, 2H), 5.47 (s, 2H), 6.39-6.60 (m, 2H), 7.35-7.59 (m, 7H), 7.95 (d, 1H), 8.18-8.23 (m, 2H)
실시예 4: 4-벤질옥시-1-(2,5-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.98 (s, 2H), 5.12 (s, 2H), 5.96-6.03 (m, 2H), 7.14- 7.39 (m, 9H)
실시예 5: 4-벤질옥시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.00 (s, 2H), 5.14 (s, 2H), 5.97-6.03 (m, 2H), 7.18-7.41 (m, 9H)
실시예 6: 4-벤질옥시-2-(4-메톡시-벤질옥시)-피리딘
1H NMR (CDCl3, 300 MHz) δ3.80 (s, 3H), 5.05 (s, 2H), 5.28 (s, 2H), 6.31 (d, 1H), 6.55 (dd, 1H), 6.90 (d, 1H), 7.29-7.40 (m, 7H), 7.99 (d, 1H)
실시예 7: 4-벤질옥시-1-(4-메톡시-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ3.79 (s, 3H), 4.98 (s, 2H), 5.01 (s, 2H), 5.92 (dd, 1H), 6.01 (d, 1H), 6.86 (d, 2H), 7.11 (d, 1H), 7.22-7.26 (m, 3H), 7.34-7.38 (m, 4H)
실시예 8: 4-벤질옥시-2-(4-메틸-벤질옥시)-피리딘
1H NMR (CDCl3, 300 MHz) δ2.37 (s, 3H), 5.06 (s, 2H), 5.33 (s, 2H), 6.34 (d, 1H), 6.56 (dd, 1H), 7.19 (d, 2H), 7.34-7.41 (m, 7H), 8.00 (d, 1H)
실시예 9: 4-벤질옥시-1-(4-메틸-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.33 (s, 3H), 4.98 (s, 2H), 5.04 (s, 2H), 5.93 (dd, 1H), 6.02 (d, 1H), 7.10-7.19 (m, 5H), 7.34-7.38 (m, 5H)
실시예 10: 4-벤질옥시-1-(6-클로로-피리딘-3-일메틸)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.99 (s, 2H), 5.04 (s, 2H), 6.00-6.02 (m, 2H), 7.15-7.38 (m, 7H), 7.66 (dd, 1H), 8.34-8.37 (m, 1H)
실시예 11: 4-벤질옥시-1-(3-클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.96 (s, 2H), 5.01 (s, 2H), 5.94 (dd, 1H), 6.00 (d, 1H), 7.09-7.36 (m, 10H)
실시예 12: 1-벤질-4-벤질옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.96 (s, 2H), 5.06 (s, 2H), 5.92 (dd, 1H), 6.01 (d, 1H), 7.10 (d, 1H), 7.24-7.36 (m, 10H)
실시예 13: 1-(4-아미노-벤질)-4-벤질옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ3.73 (br s, 2H), 4.95 (s, 2H), 4.97 (s, 2H), 5.90 (dd, 1H), 6.00 (d, 1H), 6.63 (d, 2H), 7.08-7.37 (m, 8H)
실시예 14: 1-(2,4-다이클로로-벤질)-4-하이드록시-1H-피리딘-2-온
실시예 1과 동일한 방법으로 합성한 4-벤질옥시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온을 Pd/C를 이용해서 수소화하여 표제 화합물을 수득하였다.
1H NMR (CD3OD, 300 MHz) δ 5.17 (s, 2H), 5.86 (d, 1H), 6.10 (dd, 1H), 6.99 (d, 1H), 7.27-7.32 (m, 1H), 7.50-7.52 (m, 2H)
실시예 15: 3-벤질-1-(2,4-다이클로로-벤질)-4-하이드록시-1H-피리딘-2-온
실시예 14에서 합성된 1-(2,4-다이클로로-벤질)-4-하이드록시-1H-피리딘-2-온을 DMF에 용해하고 나서, NaH 및 벤질 브로마이드를 첨가하여 4-벤질옥시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온 및 표제 화합물을 1:1의 비율로 수득하였다.
1H NMR (CDCl3, 300 MHz) δ 4.00 (s, 2H), 5.13 (s, 2H), 5.87 (d, 1H), 7.25-7.33 (m, 9H)
실시예 16 내지 225: 출발 물질을 제외하고는 실시예 1의 과정을 반복하여 표제 화합물을 수득하였다.
실시예 16: 4-(바이페닐-4-일메톡시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.04 (s, 2H), 5.15 (s, 2H), 6.01 (dd, 1H), 6.06 (d, 1H), 7.22-7.63 (m, 13H)
실시예 17: 1-(2,4-다이클로로-벤질)-4-(2,4-다이클로로-벤질옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.06 (s, 2H), 5.15 (s, 2H), 5.99-6.01 (m, 2H), 7.15-7.44 (m, 7H)
실시예 18: 4-(2-클로로-벤질옥시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.11 (s, 2H), 5.16 (s, 2H), 6.00-6.04 (m, 2H), 7.21-7.47 (m, 8H)
실시예 19: 1-(2,4-다이클로로-벤질)-4-메톡시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ3.78 (s, 3H), 5.14 (s, 2H), 5.91-5.94 (m, 2H), 7.16-7.22 (m, 3H), 7.41 (s, 1H)
실시예 20: 1-(2,4-다이클로로-벤질)-4-아이소프로폭시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.34 (d, 6H), 4.47-4.55 (m, 1H), 5.86-5.91 (m, 2H), 7.15-7.21 (m, 3H), 7.41 (s, 1H)
실시예 21: 4-사이클로헥실메톡시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.86-1.83 (m, 11H), 3.71 (d, 2H), 5.14 (s, 2H), 5.90-5.94 (m, 2H), 7.15-7.23 (m, 3H), 7.40 (s, 1H)
실시예 22: 3-(2-클로로-벤질)-4-하이드록시-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ3.82 (s, 2H), 6.12 (d, 1H), 7.06-7.28 (m, 5H)
실시예 23: 1-(2,4-다이클로로-벤질)-4-프로폭시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.02 (t, 3H), 1.74-1.85 (m, 2H), 3.88 (t, 2H), 5.14 (s, 2H), 5.91-5.94 (m, 2H), 7.15-7.24 (m, 3H), 7.40 (s, 1H)
실시예 24: 1-(2,4-다이클로로-벤질)-4-아이소부톡시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.00 (d, 6H), 2.03-2.12 (m, 1H), 3.68 (d, 2H), 5.14 (s, 2H), 5.90-5.95 (m, 2H), 7.15-7.23 (m, 3H), 7.41 (s, 1H)
실시예 25: 4-부톡시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.97 (t, 3H), 1.40-1.52 (m, 2H), 1.71-1.80 (m, 2H), 3.92 (t, 2H), 5.14 (s, 2H), 5.90-5.92 (m, 2H), 7.15-7.23 (m, 3H), 7.41 (s, 1H)
실시예 26: 1-(2,4-다이클로로-벤질)-4-옥틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.84 (t, 3H), 1.24-1.52 (m, 10H), 1.67-1.76 (m, 2H), 3.86 (t, 2H), 5.09 (s, 2H), 5.86-5.89 (m, 2H), 7.10-7.18 (m, 3H), 7.36 (s, 1H)
실시예 27: 1-(2,4-다이클로로-벤질)-4-(4-메틸-펜톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.86 (d, 6H), 1.24-1.29 (m, 2H), 1.50-1.59 (m, 1H), 1.67-1.77 (m, 2H), 3.86 (t, 2H), 5.10 (s, 2H), 5.87-5.90 (m, 2H), 7.11-7.16 (m, 3H), 7.36 (s, 1H)
실시예 28: 4-(부트-3-에닐옥시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.48 (q, 2H), 3.93 (t, 2H), 5.06-5.15 (m, 4H), 5.76-5.89 (m, 3H), 7.11-7.15 (m, 3H), 7.36 (s, 1H)
실시예 29: 1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.78-1.87 (m, 2H), 2.16 (q, 2H), 3.89 (t, 2H), 4.95-5.09 (m, 4H), 5.71-5.88 (m, 3H), 7.11-7.15 (m, 3H), 7.36 (s, 1H)
실시예 30: 1-(2,4-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.33-1.44 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.14 (s, 2H), 7.16-7.22 (m, 3H), 7.40 (d, 1H)
실시예 31: [1-(2,4-다이클로로-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시]- 아세트산 에틸에스터
1H NMR (CDCl3, 300 MHz) δ3.77 (s, 3H), 4.54 (s, 2H), 5.09 (s, 2H), 5.77 (d, 1H), 5.99 (dd, 1H), 7.17-7.22 (m, 3H), 7.37 (s, 1H)
실시예 32: 1-(2,4-다이클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.87 (d, 6H), 1.54-1.76 (m, 3H), 3.86 (t, 2H), 5.00 (s, 2H), 5.79 (dd, 1H), 5.86 (d, 1H), 7.04 (d, 1H), 7.13-7.27 (m, 3H)
실시예 33: 1-벤질-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.40 (m, 4H), 1.75-1.79 (m, 2H), 3.92 (t, 2H), 5.10 (s, 2H), 5.87-5.93 (m, 2H), 7.11 (d, 1H), 7.25-7.32 (m, 5H)
실시예 34: 1-(2-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 0.92 (t, 3H), 1.31-1.42 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.19 (S, 2H), 5.89-5.92 (m, 2H), 7.14-7.26 (m, 4H), 7.37-7.40 (m, 1H)
실시예 35: 4-펜틸옥시-1-프로필-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90-0.96 (m, 6H), 1.28-1.38 (m, 4H), 1.67-1.80 (m, 4H), 3.82 (t, 2H), 3.89 (t, 2H), 5.87 (d, 2H), 7.07-7.10 (m, 1H)
실시예 36: 1-부틸-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.89-0.96 (m, 6H), 1.29-1.42 (m, 6H), 1.64-1.78 (m, 4H), 3.83-3.91 (m, 4H), 5.86-5.88 (m, 2H), 7.07-7.10 (m, 1H)
실시예 37: 1-아이소부틸-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91-0.93 (m, 9H), 1.33-1.39 (m, 4H), 1.71-1.78 (m, 2H), 2.10-2.19 (m, 1H), 3.65 (d, 2H), 3.89 (t, 2H), 5.84-5.87 (m, 2H), 7.05 (d, 1H)
실시예 38: 1-(3-메틸-부틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90-0.96 (m, 9H), 1.33-1.39 (m, 4H), 1.55-1.78 (m, 5H), 3.84-3.91 (m, 4H), 5.86-5.88 (m, 2H), 7.07-7.10 (m, 1H)
실시예 39: 1-(2,4-다이클로로-벤질)-4-헥실옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90 (t, 3H), 1.25-1.34 (m, 4H), 1.71-1.80 (m, 2H), 3.91 (t, 2H), 5.14 (s, 2H), 5.91-5.93 (m, 2H), 7.14-7.23 (m, 3H), 7.40 (s, 1H)
실시예 40: 1-(2,4-다이클로로-벤질)-4-헵톡시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 0.75 (t, 3H), 1.09-1.54 (m, 8H), 1.71-1.80 (m, 2H), 3.91 (t, 2H), 5.13 (s, 2H), 5.86-5.92 (m, 2H), 7.14-7.22 (m, 3H), 7.40 (s, 1H)
실시예 41: 1-(4-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.33-1.42 (m, 4H), 1.71-1.80 (m, 2H), 3.90 (t, 2H), 5.04 (s, 2H), 5.87-5.91 (m, 2H), 7.08 (d, 1H), 7.20 (d, 2H), 7.30 (d, 2H)
실시예 42: 4-아릴옥시-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.48 (d, 2H), 5.14 (s, 2H), 5.32-5.45 (m, 2H), 5.94-6.07 (m, 3H), 7.18-7.20 (m, 3H), 7.41 (s, 1H)
실시예 43: 1-(2,4-다이클로로-벤질)-4-(3-메톡시-프로폭시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.01-2.07 (m, 2H), 3.35 (s, 3H), 3.52 (t, 2H), 4.02 (t, 2H), 5.14 (s, 2H), 5.91-5.94 (m, 2H), 7.16-7.20 (m, 3H), 7.41 (s, 1H)
실시예 44: 1-(2,4-다이클로로-벤질)-4-(3-에틸아미노-프로폭시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.25-1.52 (m, 5H), 2.92-3.05 (m, 4H), 4.03 (t, 2H), 5.13 (s, 2H), 5.91-5.93 (m, 2H), 7.17-7.19 (m, 3H), 7.41 (s, 1H), 8.48 (br s, 1H)
실시예 45: 1-(2,4-다이클로로-벤질)-4-(2-에톡시-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.25 (t, 3H), 3.58 (q, 2H), 3.77 (t, 2H), 4.08 (t, 2H), 5.14 (s, 2H), 5.92 (d, 1H), 5.99 (dd, 1H), 7.16-7.23 (m, 3H), 7.41 (s, 1H)
실시예 46: 1-(3-메틸-부트-2-에닐)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.33-1.38 (m, 4H), 1.71-1.73 (m, 2H), 1.76 (s, 6H), 3.89 (t, 2H), 4.47 (d, 2H), 5.27 (t, 1H), 5.87-5.88 (m, 2H), 7.10-7.13 (m, 1H)
실시예 47: 5-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-퓨란-2-카복실산 에틸에스터
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.33-1.44 (m, 7H), 1.73-1.80 (m, 2H), 3.89 (t, 2H), 4.34 (q, 2H), 5.09 (s, 2H), 5.86 (d, 1H), 5.92 (dd, 1H), 6.47 (d, 1H), 7.09 (d, 1H), 7.29 (d, 1H)
실시예 48: 5-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-퓨란-2-카복실산
1H NMR (CD3OD, 300 MHz) δ0.94 (t, 3H), 1.37-1.45 (m, 4H), 1.73-1.80 (m, 2H), 3.97 (t, 2H), 5.13 (s, 2H), 5.89 (d, 1H), 6.11 (dd, 1H), 6.41 (d, 1H), 6.93 (d, 1H), 7.65 (d, 1H)
실시예 49: 4-펜틸옥시-1-싸이아졸-4-일메틸-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.32-1.44 (m, 4H), 1.70-1.80 (m, 2H), 3.89 (t, 2H), 5.22 (s, 2H), 5.88 (d, 1H), 5.92 (dd, 1H), 7.38-7.42 (m, 2H), 8.76 (s, 1H)
실시예 50: 4-펜틸옥시-1-피리딘-3-일메틸-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.45 (m, 4H), 1.74-1.83 (m, 2H), 3.96 (t, 2H), 5.55 (s, 2H), 6.29 (d, 1H), 6.50 (dd, 1H), 7.40 (s, 1H), 7.96 (d, 1H), 8.84 (d, 1H)
실시예 51: 1-(2,4-다이클로로-벤질)-4-(4-메틸-펜트-3-에닐옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.65 (s, 3H), 1.73 (s, 3H), 2.46 (q, 2H), 3.89 (t, 2H), 5.14 (s, 2H), 5.91-5.94 (m, 2H), 7.15-7.13 (m, 3H), 7.27 (s, 1H), 7.41 (s, 1H)
실시예 52: 1-(2,4-다이클로로-벤질)-4-(3-메톡시-프로폭시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.88 (d, 6H), 1.18-1.26 (m, 4H), 1.37-1.77 (m, 5H), 3.92 (t, 2H), 5.14 (s, 2H), 5.91-5.93 (m, 2H), 7.15-7.23 (m, 3H), 7.41 (s, 1H)
실시예 53: 1-(2,4-다이클로로-벤질)-4-페네틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 3.09 (t, 2H), 4.15 (t, 2H), 5.14 (s, 2H), 5.91-5.99 (m, 2H), 7.16-7.40 (m, 9H)
실시예 54: 1-(2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.33-1.43 (m, 4H), 1.75-1.79 (m, 2H), 2.28 (s, 3H), 3.92 (t, 2H), 5.08 (s, 2H), 5.86 (dd, 1H), 5.94 (d, 1H), 6.93 (d, 1H), 7.03 (d, 1H), 7.15-7.23 (m, 3H)
실시예 55: 4-펜틸-1-페네틸-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.86 (t, 3H), 1.27-1.33 (m, 4H), 1.65-1.72 (m, 2H), 2.96 (t, 2H), 3.83 (t, 2H), 4.01 (t, 2H), 5.65 (dd, 1H), 5.83 (d, 1H), 6.65 (d, 1H), 7.08 (d, 1H), 7.13-7.25 (m, 3H)
실시예 56: 1-(2,4-다이클로로-5-플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.31-1.43 (m, 4H), 1.73-1.80 (m, 2H), 3.92 (t, 2H), 5.10 (s, 2H), 5.92-5.96 (m, 2H), 7.02 (d, 1H), 7.16 (d, 1H), 7.44 (d, 1H)
실시예 57: 1-(3,4-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.31-1.46 (m, 4H), 1.73-1.82 (m, 2H), 3.92 (t, 2H), 5.02 (s, 2H), 5.92-5.95 (m, 2H), 7.10-7.15 (m, 2H), 7.36-7.42 (m, 2H)
실시예 58: 1-(3,4-다이플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.43 (m, 4H), 1.73-1.80 (m, 2H), 3.92 (t, 2H), 5.02 (s, 2H), 5.91-5.94 (m, 2H), 7.03-7.17 (m, 4H)
실시예 59: 4-(4-벤질옥시-부톡시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.68-1.94 (m, 4H), 3.54 (t, 2H), 3.96 (t, 2H), 4.53 (s, 2H), 5.15 (s, 2H), 5.90-5.93 (m, 2H), 7.16-7.42 (m, 9H)
실시예 60: 1-(2,4-다이클로로-벤질)-4-(4-하이드록시-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.70-1.91 (m, 4H), 3.72 (t, 2H), 3.98 (t, 2H), 5.14 (s, 2H), 5.92-5.94 (m, 2H), 7.16-7.25 (m, 3H), 7.41 (s, 1H)
실시예 61: 4-(5-벤질옥시-펜틸옥시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 1.52-1.85 (m, 6H), 3.51 (t, 2H), 3.94 (t, 2H), 4.53 (s, 2H), 5.15 (s, 2H), 5.90-5.94 (m, 2H), 7.16-7.42 (m, 9H)
실시예 62: 1-(2,4-다이클로로-벤질)-4-(5-하이드록시-펜틸옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.44-1.83 (m, 6H), 3.70 (t, 2H), 3.93 (t, 2H), 5.14 (s, 2H), 5.91-5.92 (m, 2H), 7.15-7.20 (m, 3H), 7.41 (s, 1H)
실시예 63: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.35-1.43 (m, 4H), 1.74-1.79 (m, 2H), 3.91 (t, 2H), 5.10 (s, 2H), 5.88-5.91 (m, 2H), 5.96 (s, 2H), 6.81 (s, 1H), 6.84 (s, 1H), 7.18 (dd, 1H)
실시예 64: 1-(2,4-다이클로로-벤질)-4-(2-메틸-벤질옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.35 (s, 3H), 4.99 (s, 2H), 5.16 (s, 2H), 5.98 (dd, 1H), 6.08 (d, 1H), 7.20-7.42 (m, 8H)
실시예 65: 1-(2,4-다이클로로-벤질)-4-(4-메틸-벤질옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.37 (s, 3H), 4.95 (s, 2H), 5.15 (s, 2H), 5.98 (dd, 1H), 6.03 (d, 1H), 7.18-7.30 (m, 8H)
실시예 66: 1-(2-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.34-1.43 (m, 4H), 1.73-1.82 (m, 2H), 3.93 (t, 2H), 5.46 (s, 2H), 5.93 (d, 1H), 5.98 (dd, 1H), 7.10 (d, 1H), 7.17 (d, 1H), 7.44 (t, 1H), 7.56 (t, 1H), 8.10 (d, 1H)
실시예 67: 1-(2-아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.30-1.39 (m, 4H), 1.69-1.76 (m, 2H), 3.89 (t, 2H), 4.75 (br s, 2H), 5.00 (s, 2H), 5.89-5.93 (m, 2H), 6.62-6.70 (m, 2H), 7.09-7.23 (m, 3H)
실시예 68: N-[2-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.26-1.38 (m, 4H), 1.74-1.78 (m, 2H), 2.29 (s, 3H), 3.91 (t, 2H), 5.01 (s, 2H), 5.94 (d, 1H), 6.01 (dd, 1H), 7.08 (t, 1H), 7.31-7.38 (m, 3H), 8.20 (d, 1H), 10.56 (br s, 1H)
실시예 69: 4-펜틸옥시-1-(2-트라이플루오로메틸-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.31-1.42 (m, 4H), 1.75-1.81 (m, 2H), 3.95 (t, 2H), 5.32 (s, 2H), 5.93 (dd, 1H), 5.98 (d, 1H), 7.04 (d, 1H), 7.15 (d, 1H), 7.38 (t, 1H), 7.49 (t, 1H), 7.69 (d, 1H)
실시예 70: N-[4-(4-벤질옥시-2-옥소-2H-피리딘-1-일메틸)-페닐]아세트아마이드
1H NMR (CDCl3, 300 MHz) δ2.18 (s, 3H), 4.99 (s, 2H), 5.04 (s, 2H), 5.98 (dd, 1H), 6.02 (d, 1H), 7.14-7.46 (m, 10H), 7.82 (br s, 1H)
실시예 71: 1-(2,4-다이클로로-벤질)-4-(나프탈렌-2-일메톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.15 (s, 2H), 5.16 (s, 2H), 5.99-6.09 (m, 2H), 7.18- 7.55 (m, 7H), 7.83-7.90 (m, 4H)
실시예 72: 1-나프탈렌-2-일메틸-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 0.92 (t, 3H), 1.35-1.43 (m, 4H), 1.73-1.76 (m, 2H), 3.91 (t, 2H), 5.24 (s, 2H), 5.84-5.96 (m, 2H), 7.13 (d, 1H), 7.26-7.49 (m, 3H), 7.70 (s, 1H), 7.79-7.83 (m, 3H)
실시예 73: 4-벤질옥시-1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 4.99 (s, 2H), 5.10 (s, 2H), 5.94-6.03 (m, 4H), 6.84 (d, 2H), 7.20 (d, 1H), 7.33-7.39 (m, 5H)
실시예 74: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (d, 6H), 1.58-1.66 (m, 3H), 3.92 (t, 2H), 5.07 (s, 2H), 5.86 (dd, 1H), 5.90 (d, 1H), 5.93 (s, 2H), 6.80 (d, 2H), 7.14 (d, 1H)
실시예 75: 1-(2-메틸-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (d, 6H), 1.63 (q, 2H), 1.72-1.81 (m, 1H), 3.93 (t, 2H), 5.05 (s, 2H), 5.82 (dd, 1H), 5.92 (d, 1H), 6.90 (d, 1H), 7.01 (d, 1H), 7.13-7.20 (m, 3H)
실시예 76: 4-(3-메틸-부톡시)-1-(2-나이트로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (d, 6H), 1.65 (q, 2H), 1.69-1.78 (m, 1H), 3.95 (t, 2H), 5.45 (s, 2H), 5.93-5.96 (m, 2H), 7.11 (d, 1H), 7.14 (d, 1H), 7.44 (t, 1H), 7.53 (t, 1H), 8.08 (d, 1H)
실시예 77: 1-(2,4-다이클로로-벤질)-4-펜틸아미노-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.88 (t, 3H), 1.24-1.34 (m, 4H), 1.57-1.84 (m, 2H), 3.19 (br s, 1H), 3.47 (q, 2H), 5.03 (s, 2H), 5.56 (d, 1H), 7.15-7.38 (m, 4H)
실시예 78: 1-(2,3-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90 (t, 3H), 1.28-1.40 (m, 4H), 1.70-1.77 (m, 2H), 3.89 (t, 2H), 5.17 (s, 2H), 5.89-5.92 (m, 2H), 7.01 (d, 1H), 7.11-7.16 (m, 2H), 7.37 (d, 1H)
실시예 79: 1-(2-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90 (t, 3H), 1.27-1.36 (m, 4H), 1.68-1.77 (m, 2H), 3.83 (s, 3H), 3.87 (t, 2H), 5.05 (s, 2H), 5.81 (dd, 1H), 5.86 (d, 1H), 6.84-6.92 (m, 2H), 7.18-7.27 (m, 3H)
실시예 80: 1-(2,3-다이메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.89 (t, 3H), 1.29-1.38 (m, 4H), 1.67-1.74 (m, 2H), 3.81-3.88 (m, 8H), 5.08 (s, 2H), 5.80 (dd, 1H), 5.86 (d, 1H), 6.82-6.87 (m, 2H), 6.98 (t, 1H), 7.18 (d, 1H)
실시예 81: 4-(5-벤질옥시-펜틸옥시)-1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ1.47-1.53 (m, 2H), 1.61-1.66 (m, 2H), 1.74-1.78 (m, 2H), 3.48 (t, 2H), 3.96 (t, 2H), 4.45 (s, 2H), 5.06 (s, 2H), 5.90 (s, 1H), 5.94 (s, 2H), 6.06 (dd, 1H), 6.61 (s, 1H), 6.90 (s, 1H), 7.22-7.29 (m, 5H), 7.42 (d, 1H)
실시예 82: 1-(2-클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (d, 6H), 1.60-1.82 (m, 3H), 3.94 (t, 2H), 5.17 (s, 2H), 5.86-5.94 (m, 2H), 7.12-7.40 (m, 5H)
실시예 83: 1-(3,4-다이클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (d, 6H), 1.63 (q, 2H), 1.72-1.81 (m, 1H), 3.92 (t, 2H), 4.99 (s, 2H), 5.87-5.90 (m, 2H), 7.05-7.12 (m, 2H), 7.33-7.38 (m, 2H)
실시예 84: 1-(2,4-다이클로로-5-플루오로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (d, 6H), 1.64 (q, 2H), 1.71-1.82 (m, 1H), 3.93 (t, 2H), 5.08 (s, 2H), 5.90-5.92 (m, 2H), 7.00 (d, 1H), 7.12-7.15 (m, 1H), 7.42 (d, 1H)
실시예 85: 1-벤질-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.95 (d, 6H), 1.59-1.78 (m, 3H), 3.93 (t, 2H), 5.08 (s, 2H), 5.83-5.93 (m, 2H), 7.07-7.36 (m, 6H)
실시예 86: 1-(4-클로로-벤질)-4-(3-메틸-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (d, 6H), 1.62 (q, 2H), 1.71-1.80 (m, 1H), 3.91 (t, 2H), 5.01 (s, 2H), 5.85 (dd, 1H), 5.89 (d, 1H), 7.06 (d, 1H), 7.19 (d, 2H), 7.27 (d, 2H)
실시예 87: 1-(2,4-다이클로로-벤질)-4-펜틸옥시-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.88 (t, 3H), 1.32-1.36 (m, 4H), 1.61-1.73 (m, 2H), 4.33 (t, 2H), 5.07 (s, 2H), 5.83 (d, 1H), 7.22 (d, 1H), 7.35-7.45 (m, 3H)
실시예 88: 1-(2,4-다이클로로-벤질)-4-(4-메틸-펜틸옥시)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ 0.89 (d, 6H), 1.20-1.76 (m, 5H), 4.34 (t, 2H), 5.09 (s, 2H), 5.85 (d, 1H), 7.22 (d, 1H), 7.26-7.47 (m, 3H)
실시예 89: 1-(2,4-다이클로로-벤질)-4-페녹시-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.11 (d, 2H), 6.07 (d, 1H), 7.12-7.65 (m, 9H)
실시예 90: 4-(부틸-메틸-아미노)-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90 (t, 3H), 1.19-1.56 (m, 4H), 2.81-3.11 (m, 3H), 3.22-3.27 (m, 1H), 3.59-3.62 (m, 1H), 4.98 (s, 2H), 5.72-5.75 (m, 1H), 7.12-7.31 (m, 4H)
실시예 91: 1-(2,4-다이클로로-벤질)-4-(2-다이에틸아미노-에톡시)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.04 (t, 6H), 2.62 (q, 4H), 2.84 (t, 2H), 4.46 (t, 2H), 5.09 (s, 2H), 5.90 (d, 1H), 7.21-7.54 (m, 4H)
실시예 92: 4-부톡시-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.95 (t, 3H), 1.39-1.46 (m, 2H), 1.69-1.74 (m, 2H), 4.37 (t, 2H), 5.10 (s, 2H), 5.87 (d, 1H), 7.23-7.48 (m, 4H)
실시예 93: 1-(2,6-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 0.91 (t, 3H), 1.32-1.44 (m, 4H), 1.70-1.80 (m, 2H), 3.90 (t, 2H), 5.37 (s, 2H), 5.79 (dd, 1H), 5.91 (d, 1H), 6.71 (d, 1H), 7.25-7.41 (m, 3H)
실시예 94: 1-(2-클로로-6-플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.30-1.44 (m, 4H), 1.70-1.77 (m, 2H), 3.89 (t, 2H), 5.24 (s, 2H), 5.82 (dd, 1H), 5.88 (d, 1H), 6.92 (d, 1H), 7.05 (t, 1H), 7.24-7.33 (m, 2H)
실시예 95: 1-(2-메틸-3-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.33-1.43 (m, 4H), 1.75 (m, 2H), 2.40 (s, 3H), 3.92 (t, 2H), 5.13 (s, 2H), 5.92-5.95 (m, 2H), 6.98 (dd, 1H), 7.16 (d, 1H), 7.28 (t, 1H), 7.69 (d, 1H)
실시예 96: 1-(3-아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.33-1.43 (m, 4H), 1.71-1.80 (m, 2H), 2.01 (s, 3H), 3.72 (s, 2H), 3.91 (t, 2H), 5.05 (s, 2H), 5.81 (dd, 1H), 5.92 (d, 1H), 6.56 (d, 1H), 6.69 (d, 1H), 6.90 (d, 1H), 7.01 (t, 1H)
실시예 97: 1-(4-메톡시-3,5-다이메틸-피리딘-2-일메틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.30-1.41 (m, 4H), 1.70-1.77 (m, 2H), 2.23 (s, 3H), 2.30 (s, 3H), 3.75 (s, 3H), 3.89 (t, 2H), 5.16 (s, 2H), 5.85-5.88 (m, 2H), 7.28-7.30 (m, 1H), 8.19 (s, 1H)
실시예 98: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(5-하이드록시-펜틸옥시)-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ1.48-1.58 (m, 4H), 1.75-1.80 (m, 2H), 3.54 (t, 2H), 3.97 (t, 2H), 5.06 (s, 2H), 5.89 (d, 1H), 5.94 (s, 2H), 6.07 (dd, 1H), 6.61 (s, 1H), 6.90 (s, 1H), 7.43 (d, 1H)
실시예 99: 1-(2-메톡시-5-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.36-1.44 (m, 4H), 1.74-1.80 (m, 2H), 3.91 (t, 2H), 3.97 (S, 3H), 5.07 (s, 2H), 5.90-5.95 (m, 2H), 7.17 (d, 1H), 7.21 (d, 1H), 8.03 (d, 1H), 8.19 (dd, 1H)
실시예 100: 1-(5-아미노-2-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.24-1.39 (m, 4H), 1.73-1.78 (m, 2H), 3.79 (s, 2H), 3.90 (t, 2H), 5.02 (s, 2H), 5.83 (dd, 1H), 5.89 (d, 1H), 6.59-6.74 (m, 3H), 7.23-7.27 (m, 3H)
실시예 101: 1-(2-에틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.18 (t, 3H), 1.34-1.43 (m, 4H), 1.73-1.79 (m, 2H), 2.63 (q, 2H), 3.93 (t, 2H), 5.12 (s, 2H), 5.84 (dd, 1H), 5.94 (d, 1H), 6.92 (d, 1H), 7.05 (d, 1H), 7.16-7.32 (m, 3H)
실시예 102: 1-(2-클로로-5-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.46 (m, 4H), 1.72-1.82 (m, 2H), 3.94 (t, 2H), 5.19 (s, 2H), 5.94 (dd, 1H), 6.00 (d, 1H), 7.18 (d, 1H), 7.55 (d, 1H), 7.96 (d, 1H), 9.09 (dd, 1H)
실시예 103: 1-(5-아미노-2-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.31-1.43 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.11 (s, 2H), 5.87-5.91 (m, 2H), 6.52-6.55 (m, 2H), 7.11-7.18 (m, 2H)
실시예 104: 1-(4-메톡시-2,3-다이메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.31-1.42 (m, 4H), 1.72-1.81 (m, 2H), 2,12 (s, 3H), 2.16 (s, 3H), 3.82 (s, 3H), 3.91 (t, 2H), 5.04 (s, 2H), 5.80 (dd, 1H), 5.93 (d, 1H), 6.71 (d, 1H), 6.85 (d, 1H), 6.97 (d, 1H)
실시예 105: 1-(2-메틸-피리딘-3-일메틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.47 (m, 4H), 1.73-1.83 (m, 2H), 2.56 (s, 3H), 3.93 (t, 2H), 5.09 (s, 2H), 5.91-5.94 (m, 2H), 7.00 (d, 1H), 7.08-7.13 (m, 1H), 7.26-7.28 (m, 1H), 8.43 (d, 1H)
실시예 106: N-[4-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.29-1.45 (m, 4H), 1.71-1.78 (m, 2H), 2.10 (s, 3H), 3.87 (t, 2H), 5.16 (s, 2H), 5.89 (d, 1H), 5.99 (dd, 1H), 7.26-7.33 (m, 3H), 7.77 (d, 1H), 8.43 (br s, 1H)
실시예 107: 1-(2,4-다이클로로-벤질)-4-(3-다이메틸아미노-프로폭시)-1H-피리딘- 2-온
1H NMR (CDCl3, 300 MHz) δ1.87-1.97 (m, 2H), 2.25 (s, 6H), 2.40 (t, 2H), 4.42 (t, 2H), 5.10 (s, 2H), 5.87 (d, 1H), 7.23-7.49 (m, 4H)
실시예 108: 1-(2,4-다이클로로-벤질)-4-(4-다이메틸아미노-부톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.52-1.81 (m, 4H), 2.22 (s, 6H), 2.29 (t, 2H), 4.38 (t, 2H), 5.10 (s, 2H), 5.86 (d, 1H), 7.23-7.48 (m, 4H)
실시예 109: 1-(2,4-다이클로로-벤질)-4-(6-다이메틸아미노-헥실옥시)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.34-1.78 (m, 8H), 2.24-2.30 (m, 8H), 4.35 (t, 2H), 5.10 (s, 2H), 5.86 (d, 1H), 7.23-7.47 (m, 4H)
실시예 110: 1-(2,4-다이메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.33-1.42 (m, 4H), 1.71-1.76 (m, 2H), 2.22 (s, 3H), 2.31 (s, 3H), 3.91 (t, 2H), 5.03 (s, 2H), 5.83 (dd, 1H), 5.92 (d, 1H), 6.89-7.20 (m, 4H)
실시예 111: 1-(2-클로로-5-트라이플루오로메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.34-1.46 (m, 4H), 1.74-1.83 (m, 2H), 3.93 (t, 2H), 5.21 (s, 2H), 5.94-6.15 (m, 2H), 7.17 (d, 1H), 7.43-7.54 (m, 3H)
실시예 112: 1-(2-하이드록시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.29-1.43 (m, 4H), 1.70-1.79 (m, 2H), 3.90 (t, 2H), 4.99 (s, 2H), 5.97 (d, 1H), 6.04 (dd, 1H), 6.83 (t, 1H), 6.95 (dd, 1H), 7.19-7.24 (m, 2H), 7.38 (d, 1H), 10.45 (br s, 1H)
실시예 113: 4-(3-사이클로-프로폭시)-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.27-1.25 (m, 2H), 1.51-1.82 (m, 9H), 4.37 (t, 2H), 5.10 (s, 2H), 5.85 (d, 1H), 7.22 (d, 1H), 7.38-7.47 (m, 3H)
실시예 114: 1-(2,4-다이클로로-벤질)-4-(3-메틸-펜틸옥시)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.85-2.03 (m, 11H), 4.39 (t, 2H), 5.10 (s, 2H), 5.85 (d, 1H), 7.22-7.47 (m, 4H)
실시예 115: 1-(2,4-다이클로로-벤질)-4-헥스-4-에닐옥시-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.25-2.10 (m, 7H), 4.35 (t, 2H), 5.10 (s, 2H), 5.40-5.46 (m, 2H), 5.86 (d, 1H), 7.23-7.47 (m, 4H)
실시예 116: 4-(2-사이클로프로필-에톡시)-1-(2,4-다이클로로-벤질)-1H-피리미딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.42-0.96 (m, 3H), 1.25-1.66 (m, 4H), 4.43 (t, 2H), 5.10 (s, 2H), 5.87 (d, 1H), 7.22-7.47 (m, 4H)
실시예 117: 1-(2,4-다이클로로-벤질)-4-(3-메틸-펜틸옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.85-0.91 (m, 6H), 1.17-1.24 (m, 1H), 1.33-1.39 (m, 1H), 1.51-1.58 (m, 2H), 1.78-1.80 (m, 1H), 3.93 (t, 2H), 5.12 (s, 2H), 5.88-5.92 (m, 2H), 7.14-7.20 (m, 3H), 7.38 (s, 1H)
실시예 118: 1-(2,4-다이클로로-벤질)-4-(5-모폴린-4-일-펜틸옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.46-1.61 (m, 4H), 1.75-1.84 (m, 2H), 2.36 (t, 2H), 2.44 (br s, 4H), 3.73 (t, 4H), 3.92 (t, 2H), 5.14 (s, 2H), 5.90-5.92 (m, 2H), 7.16-7.23 (m, 3H), 7.41 (s, 1H)
실시예 119: 1-(2-클로로-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.33-1.43 (m, 4H), 1.72-1.79 (m, 2H), 3.74 (s, 3H), 3.91 (t, 2H), 5.15 (s, 2H), 5.88-5.93 (m, 2H), 6.76-6.79 (m, 2H), 7.15 (d, 1H), 7.27 (d, 1H)
실시예 120: 1-(2-클로로-5-에톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.25-1.40 (m, 7H), 1.72-1.81 (m, 2H), 3.89-3.99 (m, 4H), 5.15 (s, 2H), 5.89-5.92 (m, 2H), 6.75-6.77 (m, 2H), 7.15 (d, 1H), 7.26 (d, 1H)
실시예 121: 1-(2-클로로-5-프로폭시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.00 (t, 3H), 1.33-1.43 (m, 4H), 1.70- 1.81 (m, 4H), 3.84 (t, 2H), 3.92 (t, 2H), 5.15 (s, 2H), 5.88-5.93 (m, 2H), 6.74-6.78 (m, 2H), 7.15 (d, 1H), 7.26 (d, 1H)
실시예 122: 1-[2-클로로-5-(2-하이드록시-에톡시)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90 (t, 3H), 1.25-1.43 (m, 4H), 1.72-1.79 (m, 2H), 2.13 (t, 1H), 3.91 (t, 4H), 4.01 (t, 2H), 5.15 (s, 2H), 5.86-5.92 (m, 2H), 6.76-6.83 (m, 2H), 7.18 (d, 1H), 7.28 (d, 1H)
실시예 123: [4-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-옥시]-아세토나이트릴
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.33-1.43 (m, 4H), 1.73-1.82 (m, 2H), 3.92 (t, 2H),4.71 (s, 2H), 5.16 (s, 2H), 5.92-5.95 (m, 2H), 6.84-6.88 (m, 2H), 7.20 (d, 1H), 7.35 (dd, 1H)
실시예 124: 1-[5-(2-아미노-에톡시)-2-클로로-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.41-1.44 (m, 4H), 1.78-1.82 (m, 2H), 3.93 (t, 2H), 4.01 (t, 4H), 5.17 (s, 2H), 5.96 (d, 1H), 7.13 (dd, 1H), 6.60 (s, 1H), 6.90 (d, 1H), 7.34 (d, 1H), 7.49 (d, 1H)
실시예 125: N-[2-메틸-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ 0.93 (t, 3H), 1.34-1.44 (m, 4H), 1.73-1.82 (m, 2H), 2.07 (s, 3H), 2.22 (s, 3H), 3.92 (t, 2H), 5.05 (s, 2H), 5.89 (dd, 1H), 5.93 (d, 1H), 6.84 (d, 1H), 6.94 (d, 1H), 7.18 (t, 1H), 7.49 (br s, 1H), 7.56 (d, 1H)
실시예 126: 1-(2-메틸-3-메틸아미노-벤질)-4-페닐옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.27-1.40 (m, 4H), 1.73-1.78 (m, 2H), 1.98 (s, 3H), 2.90 (s, 3H), 3.69 (br s, 1H), 3.90 (t, 2H), 5.07 (s, 2H), 5.80 (dd, 1H), 5.93 (d, 1H), 6.57 (d, 1H), 6.65 (d, 1H), 6.89 (d, 1H), 7.16 (t, 1H)
실시예 127: 1-(3-다이메틸아미노-2-메틸-벤질)-4-페닐옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.36-1.43 (m, 4H), 1.75-1.79 (m, 2H), 2.22 (s, 3H), 2.69 (s, 6H), 3.92 (t, 2H), 5.07 (s, 2H), 5.86 (dd, 1H), 5.95 (d, 1H), 6.72 (d, 1H), 6.93 (d, 1H), 7.05 (d, 1H), 7.15 (t, 1H)
실시예 128: 1-(3-에틸아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.31 (t, 3H), 1.33-1.42 (m, 4H), 1.71-1.78 (m, 2H), 1.97 (s, 3H), 3.19 (q, 2H), 3.48 (br s, 1H), 3.90 (t, 2H), 5.06 (s, 2H), 5.79 (dd, 1H), 5.93 (d, 1H), 6.56 (d, 1H), 6.65 (d, 1H), 6.89 (d, 1H), 7.13 (t, 1H)
실시예 129: 1-(3-다이에틸아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.96 (t, 9H), 1.34-1.44 (m, 4H), 1.75-1.80 (m, 2H), 2.21 (s, 3H), 2.95 (q, 4H), 3.92 (t, 2H), 5.08 (s, 2H), 5.87-5.95 (m, 2H), 6.73 (d, 1H), 6.95-7.16 (m, 3H)
실시예 130: 1-(2-메틸-3-프로필아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.02 (t, 3H), 1.33-1.42(m, 4H), 1.66-1.80 (m, 4H), 1.97 (s, 3H), 3.12 (t, 2H), 3.57 (br s, 1H), 3.91 (t, 2H), 5.06 (s, 2H), 5.80 (dd, 1H), 5.93 (d, 1H), 6.55 (d, 1H), 6.65 (d, 1H), 6.90 (d, 1H), 7.13 (t, 1H)
실시예 131: 1-(3-다이프로필아미노-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.83 (t, 6H), 0.93 (t, 3H), 1.34-1.47 (m, 8H), 1.75-1.80 (m, 2H), 2.22 (s, 3H), 2.82-2.87 (m, 4H), 3.93 (t, 2H), 5.07 (s, 2H), 5.87 (dd, 1H), 5.96 (d, 1H), 6.69 (d, 1H), 6.94 (d, 1H), 7.07-7.15 (m, 2H)
실시예 132: 1-[3-(2-하이드록시-에틸아미노)-2-메틸-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.32-1.41 (m, 4H), 1.71-1.78 (m, 2H), 1.83 (br s, 1H), 2.01 (s, 3H), 3.34 (t, 2H), 3.90 (t, 4H), 4.02 (br s, 1H), 5.06 (s, 2H), 5.81 (dd, 1H), 5.92 (d, 1H), 6.57 (d, 1H), 6.67 (d, 1H), 6.89 (d, 1H), 7.12 (t, 1H)
실시예 133: 1-(2-클로로-5-메톡시-4-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.37-1.44 (m, 4H), 1.76-1.81 (m, 2H), 3.91 (s, 3H), 3.93 (t, 2H), 5.20 (s, 2H), 5.93 (d, 1H), 5.97 (dd, 1H), 7.18 (s, 1H), 7.26 (d, 1H), 7.93 (s, 1H)
실시예 134: 1-(4-아미노-2-클로로-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.32-1.42 (m, 4H), 1.71-1.78 (m, 2H), 3.81 (t, 3H),3.87-3.93 (m, 4H), 5.09 (s, 2H), 5.85 (dd, 1H), 5.90 (d, 1H), 6.69 (s, 1H), 6.91 (s, 1H), 7.21 (d, 1H)
실시예 135: N-[5-클로로-2-메톡시-4-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.35-1.42 (m,4H), 1.74-1.78 (m, 2H), 2.21 (s, 3H), 3.84 (s, 3H), 3.90 (t, 2H), 5.15 (s, 2H), 5.88-5.93 (m, 2H), 7.04 (s, 1H), 7.29 (d, 1H), 7.77 (br s, 1H), 8.46 (s, 1H)
실시예 136: 1-(2-클로로-5-메톡시-4-메틸아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.30-1.43 (m, 4H), 1.70-1.77 (m, 2H), 2.85 (s, 3H), 3.81 (s, 3H), 3.92 (t, 2H), 4.95 (s, 2H), 5.89-6.03 (m, 2H), 6.53 (s, 1H), 6.89 (s, 1H), 7.28 (d, 1H)
실시예 137: 1-(2-클로로-4-다이메틸아미노-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.95 (t, 3H), 1.40-1.44 (m, 4H), 1.75-1.81 (m, 2H), 2.76 (s, 6H), 3.80 (s, 3H), 3.99 (t, 2H), 5.14 (s, 2H), 5.95 (d, 1H), 6.10 (dd, 1H), 6.85 (s, 1H), 7.00 (s, 1H), 7.47 (d, 1H)
실시예 138: 1-(2-클로로-4-에틸아미노-5-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.28 (t, 3H), 1.36-1.41 (m, 4H), 1.71-1.77 (m, 2H), 3.13 (t, 2H), 3.80 (s, 3H), 3.89 (t, 2H), 4.23 (br s, 1H), 5.10 (s, 2H), 5.84 (dd, 1H), 5.90 (d, 1H), 6.52 (s, 1H), 6.87 (s, 1H), 7.22 (d, 1H)
실시예 139: 1-(2-클로로-5-메톡시-4-프로필아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.00 (t, 3H), 1.34-1.41 (m, 4H), 1.62-1.77 (m, 4H), 3.05 (t, 2H), 3.80 (s, 3H), 3.89 (t, 2H), 4.31 (br s, 1H), 5.09 (s, 2H), 5.83 (dd, 1H), 5.89 (d, 1H), 6.51 (s, 1H), 6.86 (s, 1H), 7.21 (d, 1H)
실시예 140: 1-[2-클로로-4-(2-하이드록시-에틸아미노)-5-메톡시-벤질]-4-펜틸옥시 -1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.32-1.42 (m, 4H),1.70-1.77 (m, 2H), 1.96 (br s, 1H), 3.30 (t, 2H), 3.79 (s, 3H), 3.82-3.91 (m, 4H), 4.73 (br s, 1H), 5.09 (s, 2H), 5.85 (dd, 1H), 5.90 (d, 1H), 6.57 (s, 1H), 6.88 (s, 1H), 7.21 (d, 1H)
실시예 141: 1-(4-아미노-6-클로로-3-메톡시-2-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.28-1.41 (m, 4H), 1.69-1.79 (m, 2H), 3.84 (s, 3H), 3.88 (t, 2H), 4.35 (br s, 2H), 4.96 (s, 2H), 5.82-5.85 (m, 2H), 6.92-7.02 (m, 2H)
실시예 142: 1-(2,4-다이아미노-6-클로로-3-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.30-1.39 (m, 4H), 1.73-1.77 (m, 2H), 3.69 (s, 3H), 3.79 (br s, 2H), 3.89 (t, 2H), 5.16 (s, 2H), 5.30 (br s, 2H), 5.88-5.94 (m, 2H), 6.17 (s, 1H), 7.56 (d, 1H)
실시예 143: 1-(2,5-다이클로로-6-메톡시-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온
H NMR (CDCl3, 300 MHz) δ 0.93 (t, 3H), 1.34-1.45 (m, 4H), 1.73-1.82 (m, 2H), 3.92 (t, 2H), 4.08 (s, 3H), 5.14 (s, 2H), 5.86 (d, 1H), 5.96 (dd, 1H), 7.19 (d, 1H)
실시예 144: 1-(2,4-다이클로로-벤젠설포닐)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.90 (t, 3H), 1.32-1.40 (m, 4H), 1.72-1.79 (m, 2H), 3.89 (t, 2H), 5.60 (d, 1H), 6.05 (dd, 1H), 7.47-7.51 (m, 2H), 7.95 (d, 1H), 8.35 (d, 1H)
실시예 145: 1-(4-메탄설포닐-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.34-1.45 (m, 4H), 1.74-1.83 (m, 2H), 3.04 (s, 3H), 3.94 (t, 2H), 5.22 (s, 2H), 5.93 (d, 1H), 5.99 (dd, 1H), 7.20 (d, 1H), 7.32 (d, 1H), 7.76 (dd, 1H), 7.97 (d, 1H)
실시예 146: 1-(4-아미노-2-클로로-5-하이드록시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.29-1.41 (m, 4H), 1.66-1.75 (m, 2H), 3.78 (t, 2H), 5.13 (s, 2H), 5.85 (d, 1H), 5.94 (dd, 1H), 6.68 (s, 1H), 7.18 (s, 1H), 7.44 (d, 1H)
실시예 147: 4-(4-브로모-부톡시)-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.88-2.08 (m, 4H), 3.46 (t, 2H), 3.95 (t, 2H), 5.13 (s, 2H), 5.88-5.92 (m, 2H), 7.16-7.24 (m, 3H), 7.40 (s, 1H)
실시예 148: 4-[1-(2,4-다이클로로-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시]-부틸암모늄
1H NMR (CD3OD, 300 MHz) δ1.82-1.90 (m, 4H), 3.00 (t, 2H), 4.07 (t, 2H), 5.19 (s, 2H), 5.97 (s, 1H), 6.14 (dd, 1H), 7.05 (d, 1H), 7.31 (dd, 1H), 7.53-7.57 (m, 2H)
실시예 149: 1-(5-클로로-2,6-다이메톡시-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.40 (m, 4H), 1.73-1.80 (m, 2H), 3.80 (s, 3H), 3.91 (t, 2H), 4.04 (s, 3H), 5.15 (s, 2H), 5.89 (d, 1H), 5.93 (dd, 1H), 7.16 (d, 1H)
실시예 150: 1-(2-아미노-5-클로로-6-메톡시-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.43 (m, 4H), 1.73-1.80 (m, 2H), 3.92 (t, 2H), 3.95 (s, 3H), 4.81 (br s, 2H), 5.08 (s, 2H), 5.90-5.93 (m, 2H), 7.10 (d, 1H)
실시예 151: 1-(6-아미노-2,5-다이클로로-피리미딘-4-일메틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.95(t, 3H), 1.31-1.44 (m, 4H), 1.73-1.79 (m, 2H), 3.91 (t, 2H), 5.08 (s, 2H), 5.60 (br s, 2H), 5.86 (d, 1H), 5.95 (dd, 1H), 7.22 (d, 1H)
실시예 152: 5-클로로-6-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-3H-벤즈옥사졸-2-온
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.38-1.46 (m, 4H), 1.76-2.05 (m, 2H), 3.97 (t, 2H), 5.11 (s, 2H), 6.01-6.07 (m, 2H), 6.72 (s, 1H), 6.73 (s, 1H), 7.22 (d, 1H), 9.35 (br s, 1H)
실시예 153: 1-(2-클로로-4-하이드록시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.30-1.41 (m, 4H), 1.70-1.80 (m, 2H), 3.90 (t, 2H), 5.09 (s, 2H), 5.94-6.01 (m, 2H), 6.60 (dd, 1H), 6.88 (d, 1H), 7.00 (d, 1H), 7.28 (d, 1H), 9.75 (br s, 1H)
실시예 154: 1-(2-클로로-4-아이소프로폭시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.31 (d, 6H), 1.35-1.45 (m, 4H), 1.73-1.80 (m, 2H), 3.90 (t, 2H), 4.46-4.54 (m, 1H), 5.11 (s, 2H), 5.85-5.91 (m, 2H), 6.74 (dd, 1H), 6.91 (d, 1H), 7.16 (d 1H), 7.23 (d, 1H)
실시예 155: 2-[3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-프로필]-아이소인돌-1,3-다이온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.20-1.33 (m, 4H), 1.71-1.80 (m, 2H), 2.09-2.18 (m, 2H), 3.75 (t, 2H), 3.87-3.94 (m, 4H), 5.86 (d, 1H), 5.91 (dd,1H), 7.27 (s, 1H), 7.72-7.76 (m, 2H), 7.83-7.87 (m, 2H)
실시예 156: 1-(3-아미노-프로필)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.36-1.44 (m, 4H), 1.75-1.80 (m, 2H), 2.26-2.30 (m, 2H), 3.00 (t, 2H), 3.91 (t, 2H), 4.10 (t, 2H), 5.90 (d, 1H), 6.02 (d, 1H), 7.25 (d, 1H)
실시예 157: N-[3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-프로필]-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.34-1.44 (m, 4H), 1.73-1.89 (m, 4H), 2.01 (s, 3H), 3.15-3.21 (m, 2H), 3.92 (t, 2H), 3.98 (t, 2H),5.89 (d, 1H), 5.98 (dd, 1H), 7.08 (br s, 1H), 7.14 (d, 1H)
실시예 158: 1-(3-다이메틸아미노-프로필)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.37-1.42 (m, 4H), 1.72-1.78 (m, 4H), 2.31-2.39 (m, 2H), 3.16-3.20 (m, 2H), 3.40 (s, 6H), 3.90 (t, 2H), 4.11 (t, 2H), 5.84 (s, 1H), 5.97 (d, 1H), 7.55 (d, 1H)
실시예 159: 1-(2,4-다이클로로-벤질)-6-메틸-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.34-1.44 (m, 4H), 1.73-1.92 (m, 2H), 2.13 (s, 3H), 3.93 (t, 2H), 5.28 (d, 2H), 5.82 (d, 1H), 5.88 (d, 1H), 6.72 (d, 1H), 7.13 (d, 1H), 7.40 (d, 1H)
실시예 160: 1-(2,4-다이클로로-벤질)-6-메틸-3-펜틸-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.85-0.98 (m, 6H), 1.30-1.48 (m, 10H), 1.75-1.78 (m, 2H), 2.18 (s, 3H), 2.55 (t, 2H), 3.99 (t, 2H), 5.33 (s, 2H), 5.94 (s, 1H), 6.65 (d, 1H), 7.12 (dd, 1H), 7.39 (d, 1H)
실시예 161: 1-(2-아미노-에틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3 + 몇 방울의 CD3OD, 300 MHz) δ0.93 (t, 3H), 1.31-1.40 (m, 4H), 1.75-1.79 (m, 2H), 2.95 (t, 2H), 3.81-4.00 (m, 4H), 5.83-5.91 (m, 2H), 7.08 (d, 1H)
실시예 162: N-[2-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-에틸]-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.31-1.42 (m, 4H), 1.72- 1.79 (m, 2H), 1.96 (s, 3H), 3.53 (q, 2H), 3.90 (t, 2H), 4.05 (t, 2H), 5.87 (d, 1H), 5.94 (dd, 2H), 6.89 (br s, 1H), 7.13 (d, 1H)
실시예 163: N-[1,1-다이메틸-2-(2-옥소-4-펜틸옥시-2H-피리딘-1-일)-에틸]-메탄설 폰아마이드
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.29-1.46 (m, 10H), 1.75-1.80 (m, 2H), 2.98 (s, 3H), 3.92 (t, 2H), 3.99 (s, 2H), 5.91-5.97 (m, 2H), 6.56 (br s, 1H), 7.23 (d, 1H)
실시예 164: N-[1-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-프로필]-메탄설폰아마이드
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.05 (t, 3H), 1.30-1.40 (m,4H), 1.59-1.81 (m, 4H), 2.75 (s, 3H), 3.65-4.15 (m, 6H), 5.75 (d, 1H), 5.91 (d, 1H), 5.97 (dd, 1H), 7.19 (d, 1H)
실시예 165: 1-(7-나이트로-벤조[1,3]다이옥솔-5-일메틸)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.95 (t, 3H), 1.32-1.42 (m, 4H),1.75-1.82 (m, 2H), 3.95 (t, 2H), 5.42 (s, 2H), 5.94-6.00 (m, 2H), 6.09 (s, 2H), 6.55 (s, 1H), 7.18 (d, 1H), 7.63 (s, 1H)
실시예 166: 1-(2-클로로-3-나이트로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.97 (t, 3H), 1.27-1.53 (m, 4H), 1.77-1.82 (m, 2H), 3.95 (t, 2H), 5.25 (s, 2H), 5.96-6.00 (m, 2H), 7.22 (d, 1H), 7.35-7.44 (m, 2H), 7.73 (d, 1H)
실시예 167: 1-(3-아미노-2-클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.37-1.43 (m, 4H), 1.72-1.76 (m, 2H), 3.89 (t, 2H), 4.13 (br s), 5.12 (s, 2H), 5.86-5.92 (m, 2H), 6.47 (d, 1H), 6.70 (d, 1H), 6.96-7.07 (m, 2H)
실시예 168: N-[2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.27-1.44 (m, 4H), 1.74-1.81 (m, 2H), 2.26 (s, 3H), 3.93 (t, 2H), 5.19 (s, 2H), 5.90-5.94 (m, 2H), 6.87 (d, 1H), 7.06 (d, 1H), 7.23 (d, 1H), 7.69 (br s, 1H), 8.30 (d, 1H)
실시예 169: N-[2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-메탄설폰아마이드
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.37-1.43 (m, 4H), 1.75-1.81 (m, 2H), 3.03 (s, 3H), 3.94 (t, 2H), 5.18 (s, 2H), 5.94-5.97 (m, 2H), 6.90 (d, 1H), 7.00 (br s, 1H), 7.12 (d, 1H), 7.28 (d, 1H), 7.60 (d, 1H)
실시예 170: N,N'-[2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐]-다이메탄설폰아마이드
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.26-1.41 (m, 4H), 1.76-1.81 (m, 2H), 3.49 (s, 6H), 3.94 (t, 2H), 5.23 (s, 2H), 5.94-5.96 (m, 2H), 7.15 (d, 1H), 7.25-7.38 (m, 3H)
실시예 171: 1-[2-클로로-3-(2-하이드록시-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.28-1.38 (m, 4H), 1.74-1.79 (m, 2H), 2.00 (br s, 1H), 3.37 (br s, 2H), 3.89-3.94 (m, 4H), 4.74 (br s, 1H), 5.15 (s, 2H), 5.87 (dd, 1H), 5.93 (d, 1H), 6.48 (d, 1H), 6.66 (d, 1H), 7.05-7.12 (m, 2H)
실시예 172: 4-클로로-2-(2-클로로-벤질)-5-펜틸옥시-2H-피리다진-3-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.30-1.47 (m, 4H), 1.70-1.79 (m, 2H), 4.59 (t, 2H), 5.43 (s, 2H), 7.07-7.10 (m, 1H), 7.18-7.26 (m, 2H), 7.38 (dd, 1H), 7.74 (s, 1H)
실시예 173: 2-(2-클로로-벤질)-5-펜틸옥시-2H-피리다진-3-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.26-1.49 (m, 4H), 1.85-1.94 (m, 2H), 3.99 (t, 2H), 5.49 (s, 2H), 6.38 (d, 1H), 7.16- 7.39 (m, 4H), 7.67 (d, 1H)
실시예 174: 1-(3-아미노-2,6-다이클로로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.25-1.44 (m, 4H), 1.70-1.80 (m, 2H), 3.90 (t, 2H), 4.19 (s, 2H), 5.33 (s, 2H), 5.79 (dd, 1H), 5.92 (d, 1H), 6.74 (dd, 2H), 7.18 (d, 1H)
실시예 175: 1-(3-벤질옥시-2-클로로-4-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.35-1.43 (m, 4H), 1.72-1.79 (m, 2H), 3.84 (s, 3H), 3.90 (t, 2H), 5.02 (s, 2H), 5.12 (s, 2H), 5.84-5.91 (m, 2H), 6.79 (d, 1H), 7.01 (d, 1H), 7.11 (d, 1H), 7.33-7.40 (m, 3H), 7.49-7.54 (m, 2H)
실시예 176: 1-(2-클로로-3,4-다이메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.27-1.41 (m, 4H), 1.74-1.80 (m, 2H), 3.86-3.94 (m, 8H), 5.13 (s, 2H), 5.87-5.92 (m, 2H), 6.80 (d, 1H), 7.03 (d, 1H), 7.18 (d, 1H)
실시예 177: 1-(2-클로로-3-하이드록시-4-메톡시-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.95 (t, 3H), 1.26-1.39 (m, 4H), 1.73-1.76 (m, 2H), 3.89-3.93 (m, 5H), 5.13 (s, 2H), 5.86-5.90 (m, 2H), 6.75 (d, 1H), 6.83 (d, 1H), 7.13 (d, 1H)
실시예 178: 1-[2-클로로-4-메톡시-3-(2-메톡시-에톡시)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.26-1.39 (m, 4H), 1.74-1.82 (m, 2H), 3.45 (s, 3H), 3.74 (t, 2H), 3.84 (s, 3H), 3.91 (t, 2H), 4.15 (t, 2H), 5.12 (s, 2H), 5.86-5.91 (m, 2H), 6.78 (d, 1H), 7.00 (d, 1H), 7.15 (d, 1H)
실시예 179: 1-[2-클로로-4-메톡시-3-(2-피롤리딘-1-일-에톡시)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 0.93 (t, 3H), 1.33-1.39(m, 4H), 1.77-1.84 (m, 6H), 2.71 (m, 4H), 2.97 (t, 2H), 3.83 (s, 3H), 3.91 (t, 2H), 4.13 (t, 2H), 5.12 (s, 2H), 5.86-5.92 (m, 2H), 6.78 (d, 1H), 7.00 (d, 1H), 7.15 (d, 1H)
실시예 180: 1-[2-클로로-3-(2-다이메틸아미노-에톡시)-4-메톡시-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.33-1.42 (m, 4H), 1.75-1.82 (m, 2H), 2.41 (s, 6H), 2.83 (t, 2H), 3.97 (t, 2H), 4.11 (t, 2H), 5.13 (s, 2H), 5.94 (s, 1H), 6.04 (dd, 1H), 6.87 (dd, 1H), 6.94 (dd, 1H), 7.27 (d, 1H)
실시예 181: 2-{3-[2-클로로-6-메톡시-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페녹실]-프로필}-아이소인돌-1,3-다이온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.28-1.38 (m, 4H), 1.73-1.77 (m, 2H), 3.59 (s, 3H), 3.89 (t, 2H), 4.12 (t, 2H), 4.26 (t, 2H), 5.03 (s, 2H), 5.85-5.91 (m, 2H), 6.69 (d, 1H), 6.95 (d, 1H), 7.08 (d, 1H), 7.74 (d, 2H), 7.87 (d, 2H)
실시예 182: 1-[3-(2-다이메틸아미노-에톡시)-2-메틸-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.94 (t, 3H), 1.26-1.35 (m, 4H), 1.75-1.79 (m, 2H), 2.15 (s, 3H), 2.37 (s, 6H), 2.79 (t, 2H), 3.93 (t, 2H), 4.09 (t, 2H), 5.08 (s, 2H), 5.83-5.94 (m, 2H), 6.70 (d, 1H), 6.83-6.92 (m, 2H), 7.15 (t, 1H), 7.28 (s, 1H)
실시예 183: 1-[2-클로로-3-(2-다이메틸아미노-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.30-1.40 (m, 4H), 1.55-1.59 (m, 2H), 2.29 (s, 6H), 2.62 (t, 2H), 3.20 (t, 2H), 3.92 (t, 2H), 5.00 (br s, 1H), 5.16 (s, 2H), 5.86-5.93 (m, 2H), 6.47 (d, 1H), 6.61 (d, 1H), 7.06-7.13 (m, 2H)
실시예 184: 1-[2,6-다이클로로-3-(2-하이드록시-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.91 (t, 3H), 1.32-1.42 (m, 4H), 1.72-1.79 (m, 2H), 2.54 (t, 1H), 3.36 (q, 2H), 3.87-3.94 (m, 4H), 4.84 (t, 1H), 5.27 (s, 2H), 5.78 (dd, 1H), 5.91 (d, 1H), 6.68-6.71 (m, 2H), 7.23 (d, 1H)
실시예 185: 1-[2,6-다이클로로-3-(2-다이메틸아미노-에틸아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ0.93 (t, 3H), 1.38-1.46 (m, 4H), 1.75-1.80 (m, 2H), 2.55 (s, 6H), 2.91 (t, 2H), 3.46 (t, 2H), 3.99 (t, 2H), 5.32 (s, 2H), 5.96 (d, 1H), 6.02 (dd, 1H), 6.88 (d, 1H), 6.93 (d, 1H), 7.35 (d, 1H)
실시예 186: 1-[2,6-다이클로로-3-(3-하이드록시-프로필아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ0.93 (t, 3H), 1.38-1.45 (m, 4H), 1.75-1.90 (m, 4H), 3.48-3.53 (m, 2H), 3.69 (t, 2H), 3.98 (t, 2H), 5.31 (s, 2H), 5.95 (d, 1H), 6.01 (dd, 1H), 6.83 (d, 1H), 6.90 (d, 1H), 7.30 (d, 1H)
실시예 187: 1-[2,6-다이클로로-3-(3-다이메틸아미노-프로필아미노)-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3 + 몇 방울의 CD3OD, 300 MHz) δ0.79 (t, 3H), 1.13-1.30 (m, 4H), 1.61-1.77 (m, 4H), 2.20 (s, 6H), 2.38 (t, 2H), 3.11 (t, 2H), 3.80 (t, 2H), 5.18 (s, 2H), 5.76 (dd, 1H), 5.81 (d, 1H), 6.54 (d, 1H), 6.64 (d, 1H), 7,13 (d, 1H)
실시예 188: 1-[3-(3-아미노-프로필아미노)-2,6-다이클로로-벤질]-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ0.94 (t, 3H), 1.38-1.46 (m, 4H), 1.75-1.80 (m, 2H), 1.94-2.01 (m, 2H), 3.01-3.06 (m, 2H), 3.32-3.39 (m, 2H), 3.99 (t, 2H), 5.31 (s, 2H), 5.95 (d, 1H), 6.02 (dd, 1H),6.87 (d, 1H), 6.92 (d, 1H), 7.33 (d, 1H)
실시예 189: 1-(3-플루오로-2-메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.32-1.46 (m, 4H), 1.75-1.78 (m, 2H), 2.19 (s, 3H), 3.93 (t, 2H), 5.08 (s, 2H), 5.86-5.94 (m, 2H), 6.82 (d, 1H), 6.92-7.02 (m, 2H), 7.10-7.15 (m, 1H)
실시예 190: 1-(2-클로로-3-다이메틸아미노메틸-4-플루오로-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.33-1.45 (m, 4H), 1.72-1.86 (m, 2H), 3.55 (s, 6H), 3.91 (t, 2H), 4.91 (s, 2H), 5.19 (s, 2H), 5.88 (d, 1H), 5.98 (dd, 1H), 7.12-7.42 (m, 3H)
실시예 191: 1-(2,6-다이클로로-3-메틸아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.32-1.42 (m, 4H), 1.75-1.79 (m, 2H), 2.91 (d, 3H), 3.90 (t, 2H), 4.49 (q,1H), 5.33 (s, 2H), 5.78 (dd, 1H), 5.92 (d, 1H), 6.63 (d, 1H), 6.70 (d, 1H), 7.28 (d, 1H)
실시예 192: 1-(2,6-다이클로로-3-다이메틸아미노-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.92 (t, 3H), 1.34-1.41 (m, 4H), 1.72-1.78 (m, 2H), 2.80(s, 6H), 3.90 (t, 2H), 5.38 (s, 2H), 5.79 (dd, 1H), 5.93 (d, 1H), 6.69 (d, 1H), 7.08 (d, 1H), 7.33 (d, 1H)
실시예 193: [2-클로로-3-(2-옥소-4-펜틸옥시-2H-피리딘-1-일메틸)-페닐아미노]-아세트산
1H NMR (DMSO-d6, 300 MHz) δ0.89 (t, 3H), 1.32-1.37 (m, 4H), 1.67-1.71 (m, 2H), 3.90-3.97 (m, 4H), 5.03 (s, 2H), 5.69 (br s, 1H), 5.83 (s, 1H), 5.99 (d, 1H), 6.05 (d, 1H), 6.52 (d, 1H), 7.05 (t, 1H), 7.51 (d, 1H)
실시예 194: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(피리딘-4-일메톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.02 (s, 2H), 5.09 (s, 2H), 5.95-6.01 (m, 4H), 6.84 (d, 1H)7.21-7.31 (m, 4H), 8.62 (d, 2H)
실시예 195: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(6-클로로-피리딘-3-일메톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 4.98 (s, 2H), 5.09 (s, 2H), 5.92-5.99 (m, 4H), 6.83 (d, 1H), 7.22-7.40 (m, 3H), 7.70 (dd, 1H), 8.40 (dd, 1H)
실시예 196: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(4-메톡시-3,5-다이메틸피리딘-2-일메톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 2.27 (s, 6H), 3.78 (s, 3H), 5.09 (s, 4H), 6.09-6.10 (m, 4H), 6.84 (s, 2H), 7.17 (s, 1H), 7.21 (s, 1H), 8.25 (s, 1H)
실시예 197: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-메틸-피리딘-3-일메톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 2.58 (s, 3H), 5.00 (s, 2H), 5.13 (s, 2H), 5.96-5.98 (m, 3H), 6.05 (d, 1H), 6.87 (d, 2H), 7.19 (dd, 1H), 7.25-7.29 (m, 1H), 7.67 (d, 1H), 8.51 (d, 1H)
실시예 198: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(싸이아졸-4-일메톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 5.12 (s, 2H), 5.21 (s, 2H), 5.98 (s, 2H), 6.01 (dd, 1H), 6.07 (d, 1H), 6.86 (d, 2H), 7.24 (d, 1H), 7.43 (s, 1H), 8.87 (s, 1H)
실시예 199: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(피리딘-2-일메톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ5.12 (s, 2H), 5.16 (s, 2H), 5.98 (s, 2H), 6.03-6.05 (m, 2H), 6.86 (d, 2H), 7.25-7.29 (m, 2H), 7.45 (d, 1H), 7.75 (td, 1H), 8.63 (d, 1H)
실시예 200: 펜탄산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘-4-일 에스터
H NMR (CDCl3, 300 MHz) δ 0.97 (t, 3H), 1.39-1.47 (m, 2H), 1.68-1.75 (m, 2H), 2.54 (t, 2H), 5.15 (s, 2H), 5.98 (s, 2H), 6.09 (dd, 1H), 6.38 (d, 1H), 6.86 (s, 1H), 6.91 (s, 1H), 7.37 (d, 1H)
실시예 201: 헥산산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘-4-일 에스터
1H NMR (CDCl3, 300 MHz) δ0.93 (t, 3H), 1.34-1.38 (m, 4H), 1.70-1.76 (m, 2H), 2.54 (t, 2H), 5.16 (s, 2H), 5.98 (s, 2H), 6.10 (dd, 1H), 6.40 (d, 1H), 6.87 (s, 1H), 6.91 (s, 1H), 7.37 (d, 1H)
실시예 202: 1-(2-클로로-3-트라이플루오로메틸-벤질)-4-펜틸옥시-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.95 (t, 3H), 1.37-1.45 (m, 4H), 1.78-1.81 (m, 2H), 3.94 (t, 2H), 5.25 (s, 2H), 5.95-5.98 (m, 2H), 7.19-7.38 (m, 3H), 7.65 (d, 1H)
실시예 203: 싸이오펜-2-카복실산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘-4-일 에스터
1H NMR (CDCl3, 300 MHz) δ5.19 (s, 2H), 6.00 (s, 2H), 6.24 (dd, 1H), 6.53 (d, 1H), 6.88 (s, 1H), 6.94 (s, 1H), 7.21 (t, 1H), 7.42 (d, 1H), 7.72 (d, 1H), 7.98 (d, 1H)
실시예 204: 톨루엔-4-설폰산 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-2-옥소-1,2-다이하이드로-피리딘-4-일 에스터
1H NMR (CDCl3, 300 MHz) δ2.48 (s, 3H), 5.10 (s, 2H), 6.00 (s, 2H), 6.14-6.15 (m, 2H), 6.84 (s, 1H), 6.87 (s, 1H), 7.34-7.35 (m, 1H), 7.38 (d, 2H), 7.81 (d, 2H)
실시예 205: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(4,4,5,5,5-펜타플루오로-펜틸옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.08-2.28 (m, 4H), 4.01 (t, 2H), 5.12 (s, 2H), 5.91-5.93 (m, 2H), 5.98 (s, 2H), 6.84 (s, 1H), 6.87 (s, 1H), 7.22-7.24 (m, 1H)
실시예 206: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-다이메틸아미노-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.33 (s, 6H), 2.73 (t, 2H), 4.03 (t, 2H), 5.11 (s, 2H), 5.94-5.97 (m, 4H), 6.83 (s, 1H), 6.86 (s, 1H), 7.19 (d, 1H)
실시예 207: 4-클로로-2-(2,4-다이클로로-벤질옥시)-피리딘
1H NMR (CDCl3, 300 MHz) δ5.17 (s, 2H), 6.83 (dd, 1H), 6.93 (d, 1H), 7.28-7.47 (m, 3H), 8.23 (d, 1H)
실시예 208: 4-클로로-1-(2,4-다이클로로-벤질)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 5.17 (s, 2H), 6.21 (dd, 1H), 6.65 (s, 1H), 7.22-7.42 (m, 3H), 7.43 (s, 1H)
실시예 209: 1-(2,4-다이클로로-벤질)-4-(5-플루오로-펜틸옥시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.58-1.61 (m, 2H), 1.74-1.88 (m, 4H), 3.96 (t, 2H), 4.44 (t, 1H), 4.54 (t, 1H), 5.16 (s, 2H), 5.93-5.94 (m, 2H), 7.18-7.22 (m, 3H), 7.42 (s, 1H)
실시예 210: 3-[1-(2,4-다이클로로-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시메틸]-인돌-1-카복실산 테트라-부틸 에스터
1H NMR (CDCl3, 300 MHz) δ1.61 (s, 9H), 5.18 (s, 2H), 5.40 (s, 2H), 5.95 (dd, 1H), 6.15 (d, 1H), 7.21-7.60 (m, 7H), 8.23 (d, 1H)
실시예 211: 1-(2,4-다이클로로-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ3.30 (t, 2H), 4.15 (t, 2H), 5.13 (s, 2H), 5.90-5.97 (m, 2H), 6.87-6.98 (m, 2H), 7.15-7.22 (m, 4H), 7.41 (s, 1H)
실시예 212: 1-(2,4-다이클로로-벤질)-4-(2-싸이오펜-3-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ3.12 (t, 2H), 4.15 (t, 2H), 5.12 (s, 2H), 5.88-5.97 (m, 2H), 6.95-7.41 (m, 7H)
실시예 213: 1-(2,4-다이클로로-벤질)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.18 (t, 2H), 4.28 (t, 2H), 5.14 (s, 2H), 5.82-5.97 (m, 2H), 6.70-6.80 (m, 2H), 7.10-7.25 (m, 3H), 7.40 (s, 1H)
실시예 214: 1-(2,4-다이클로로-벤질)-4-(3-피롤-1-일-프로폭시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.20 (m, 2H), 3.82 (t, 2H), 4.03 (t, 2H), 5.14 (s, 2H), 5.86 (d, 1H), 5.94 (dd, 1H), 6.12-6.18 (m, 2H), 6.60-6.66 (m, 2H), 7.18-7.24 (m, 3H), 7.40 (s, 1H)
실시예 215: 1-(3-아미노-2-메틸-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.01 (s, 3H), 3.28 (t, 2H), 3.65 (br s, 2H), 4.14 (t, 2H), 5.04 (s, 2H), 5.84 (dd, 1H), 5.95 (d, 1H), 6.57 (d, 1H), 6.70 (d, 1H), 6.88-7.02 (m, 4H), 7.16 (dd, 1H)
실시예 216: 1-(3-아미노-2-메틸-벤질)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.01 (s, 3H), 4.16 (t, 2H), 4.25 (t, 2H), 5.04 (s, 2H), 5.83 (dd, 1H), 5.90 (d, 1H), 6.16 (t, 2H), 6.57 (d, 1H), 6.71-6.75 (m, 3H), 6.91 (d, 1H), 7.02 (t, 1H)
실시예 217: 1-(3-아미노-2-메틸-벤질)-4-[2-(4-메틸-싸이아졸-5-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.98 (s, 3H), 2.40 (s, 3H), 3.20 (t, 2H), 3.46 (br s, 2H), 4.06 (t, 2H), 5.02 (s, 2H), 5.81 (dd, 1H), 5.92 (d, 1H), 6.53 (d, 1H), 6.68 (d, 1H), 6.91 (d, 1H), 6.99 (t, 1H), 8.56 (s, 1H)
실시예 218: 1-(3-아미노-2-메틸-벤질)-4-(2-(5-브로모싸이오펜-2-일)-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.95 (s, 3H), 3.14 (t, 2H), 3.49 (br s, 2H), 4.05 (t, 2H), 4.99 (s, 2H), 5.81 (dd, 1H), 5.88 (m, 1H), 6.49 (d, 1H), 6.60 (m, 1H), 6.64 (d, 1H), 6.83 (m, 1H), 6.89 (dd, 1H), 6.96 (t, 1H)
실시예 219: 1-(3-아미노-2-메틸-벤질)-4-(2-(5-플루오로싸이오펜-2-일)-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.02 (s, 3H), 3.12 (dt, 2H), 4.09 (t, 2H), 5.05 (s, 2H), 5.85 (dd, 1H), 5.93 (d, 1H), 6.28 (dd, 1H), 6.46 (d, 1H), 6.58 (d, 1H), 6.72 (d, 1H), 6.92 (d, 1H), 7.03 (t, 1H)
실시예 220: 1-[3-(2-하이드록시-에틸아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 1.96 (s, 3H), 3.29 (m, 4H), 3.88 (t, 2H), 4.12 (t, 2H), 5.02 (s, 2H), 5.84 (dd, 1H), 5.93 (d, 1H), 6.53 (d, 1H), 6.66 (d, 1H), 6.92 (m, 3H), 7.10 (t, 1H), 7.16 (dd, 1H)
실시예 221: 2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ2.01 (s, 3H), 3.22 (t, 2H), 3.60 (d, 2H), 4.17 (t, 2H), 4.97 (s, 2H), 5.86 (m, 1H), 5.94 (dd, 1H), 6.20 (d, 1H), 6.29 (d, 1H), 6.95 (m, 3H), 7.33 (m, 2H)
실시예 222: 1-[3-(사이클로프로필메틸-아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ0.25 (dt, 2H), 0.57 (dt, 2H), 1.06-1.19 (m, 1H), 2.01 (s, 3H), 2.98 (d, 2H), 3.27 (t, 2H), 3.73 (br s, 1H), 4.14 (t, 2H), 5.05 (s, 2H), 5.82 (dd, 1H), 5.94 (d, 1H), 6.87-6.95 (m, 3H), 7.10 (t, 1H)
실시예 223: N-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-아세토나이트릴
1H NMR (CDCl3, 300 MHz) δ2.00 (s, 3H), 3.28 (t, 2H), 4.14 (m, 4H), 5.07 (s, 2H), 5.87 (dd, 1H), 5.93 (d, 1H), 6.66 (d, 1H), 6.71 (d, 1H), 6.93-6.96 (m, 3H), 7.15-7.19 (m, 2H)
실시예 224: N-(2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-에틸)-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ1.99 (m, 6H), 3.26-3.32 (m, 4H), 3.53-3.59 (m, 2H), 4.14 (t, 2H), 5.05 (s, 2H), 5.82 (dd, 1H), 5.94 (d, 1H), 6.52 (d, 1H), 6.61(d, 1H), 6.89-6.69 (m, 3H), 7.10 (t, 1H), 7.15 (d, 1H)
실시예 225: 1-[2-메틸-3-(2-피롤-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 1.85 (s, 3H), 3.28 (t, 2H), 3.51 (t, 3H), 4.14 (t, 4H), 5.05 (s, 2H), 5.84 (dd, 1H), 5.93 (d, 1H), 6.17 (m, 2H), 6.56 (d, 1H), 6.65 (m, 3H), 6.90 (m, 3H), 7.10-7.17 (m, 2H)
실시예 226: 1-[2-메틸-3-(2-옥소-2-피롤리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온의 합성
{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-아세트산(50mg, 0.13mmol), TBTU(60mg, 0.19mmol), 피롤리딘(0.02ml, 0.25mmol) 및 트라이에틸아민(0.09ml, 0.63mmol)의 혼합물을 N,N-다이메틸포름아마이드(0.5ml)에 용해시키고 상온에서 교반하였다. 1시간 후에, 생성 용액을 증발시 키고, 다이클로로메탄(20ml)으로 추출한 후, 실리카 겔 컬럼 크로마토그래피(에틸 아세테이트/MeOH, 20:1)에 가하여 표제 화합물(41mg, 71%)을 수득하였다.
1H NMR (CDCl3, 300 MHz) δ1.88-1.95 (m, 2H), 1.99-2.09 (m, 5H), 3.27 (t, 2H), 3.44 (t, 2H), 3.55 (t, 2H), 3.81 (s, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.95 (d, 1H), 6.51 (d, 1H), 6.54 (d, 1H), 6.87-6.94 (m, 3H), 7.10 (t, 1H) 7.16 (dd, 1H)
실시예 227 내지 230: 출발 물질을 제외하고는 실시예 226의 과정을 반복하여 표제 화합물을 수득하였다.
실시예 227: 1-[2-메틸-3-(2-옥소-2-피페리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 1.53-1.74 (m, 6H), 2.07 (s, 3H), 3.27 (t, 2H), 3.39 (t, 2H), 3.62 (t, 2H), 3.88 (s, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.95 (d, 1H), 6.52 (d, 1H), 6.84-6.96 (m, 3H), 7.10 (t, 1H) 7.16 (dd, 1H)
실시예 228: N,N-다이메틸-2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피 리딘-1-일메틸]-페닐아미노}-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ2.08 (s, 3H), 3.05 (s, 6H), 3.28 (t, 2H), 3.88 (s, 2H), 4.15 (t, 2H), 5.07 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.50-6.55 (m, 2H), 6.89-6.96 (m, 3H), 7.08-7.17 (m, 2H)
실시예 229: 1-{2-메틸-3-[2-(4-메틸-피페라진-1-일)-2-옥소-에틸아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.07 (s, 3H), 2.33 (s, 3H), 2.45 (d, 4H), 3.28 (t, 2H), 3.48 (d, 2H), 3.70 (d, 2H), 3.89 (s, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.52 (dd, 2H), 6.88-6.97 (m, 3H), 7.08-7.17 (m, 2H)
실시예 230: 1-[2-메틸-3-(2-모폴린-4-일-2-옥소-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.08 (s, 3H), 2.28 (t, 2H), 3.48 (t, 2H), 3.62-3.79 (m, 6H), 3.90 (s, 2H), 4.15 (t, 2H), 5.07 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.48 (d, 1H), 6.54 (d, 1H), 6.88-6.96 (m, 3H), 7.08-7.18 (m, 2H)
실시예 231 내지 266: 출발 물질을 제외하고는 실시예 1의 과정을 반복하여 표제 화합물을 수득하였다.
실시예 231: 1-(3-아미노-2-메틸-벤질)-4-(2-퓨란-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.01 (s, 3H), 3.10 (t, 2H), 4.17 (t, 2H), 5.05 (s, 2H), 5.81 (dd, 1H), 5.95 (d, 1H), 6.10 (d, 1H), 6.30 (d, 1H), 6.57 (d, 1H), 6.69 (d, 1H), 6.90 (d, 1H), 7.02(t, 1H), 7.29 (d, 1H)
실시예 232: 1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ 2.02(s, 3H), 2.40 (s, 3H), 3.19 (t, 2H), 4.16 (t, 2H), 5.07(s, 2H), 5.96 (d, 1H), 6.06 (dd, 1H), 6.40 (d, 1H), 6.57 (dd, 1H), 6.67 (d, 1H), 6.73 (d, 1H), 6.95 (t, 1H), 7.21 (d, 1H)
실시예 233: 1-(3-아미노-2-메틸-벤질)-4-[2-(5-클로로-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.01(s, 3H), 3.18 (t, 2H), 3.70 (br s, 2H), 4.10 (t, 2H), 5.05 (s, 2H), 5.84 (dd, 1H), 2.92 (d, 1H), 6.57 (d, 1H), 6.65 (d, 1H), 6.69 (d, 1H), 6.74 (d, 1H), 6.92 (d, 1H), 7.02 (t, 1H)
실시예 234: 1-(2,4-다이클로로-벤질)-4-[2-(3-메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 2.20(s, 3H), 3.20 (t, 2H), 4.10 (t, 2H), 5.14 (s, 2H), 5.93-5.97 (m, 2H), 6.80 (d, 1H), 7.07 (d, 1H), 7.17-7,20 (m, 3H), 7.40 (s, 1H)
실시예 235: 1-(3-아미노-2-메틸-벤질)-4-(2-벤조[b]싸이오펜-3-일-에톡시)-1H-피리딘-2-온
1H NMR (CD3OD, 300 MHz) δ2.00 (s, 3H), 3.31 (t, 2H), 4.31 (t, 2H), 5.04 (s, 2H), 5.96-6.01 (m, 2H), 6.37 (d, 1H), 6.72 (d, 1H), 6.93 (t, 1H), 7.14-7.42 (m, 5H), 7.84 (t, 1H)
실시예 236: 1-(3-아미노-2-메틸-벤질)-4-[2-(5-클로로-3-메틸-벤조[b]싸이오펜-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CD3OD + 몇 방울의 CDCl3, 300 MHz) δ1.97 (s, 3H), 2.32 (s, 3H), 3.32 (t, 2H), 4.20 (t, 2H), 5.01 (s, 2H), 5.92-5.97 (m, 2H), 6.45 (d, 1H), 6.71 (d, 1H), 6.96 (t, 1H), 7.02 (d, 1H), 7.21 (dd, 1H), 7.55 (d, 1H), 7.65 (d, 1H)
실시예 237: 1-(3-아미노-2-메틸-벤질)-4-[2-(3-메틸-벤조[b]싸이오펜-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 2.00(s, 3H), 2.36 (s, 3H), 3.33 (t, 2H), 3.73 (br s,2H), 4.18 (t, 2H), 5.05 (s, 2H), 5.82 (dd, 1H), 5.95 (d, 1H), 6.56 (d, 1H), 6.69 (d, 1H), 6.91 (d, 1H), 7.02 (t, 1H), 7.27-7.39 (m, 2H), 7.63 (d, 1H), 7.77 (d, 1H)
실시예 238: 1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸-퓨란-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.00 (s, 3H), 2.24 (s, 3H), 3.03 (t, 2H), 4.13 (t, 2H), 5.03 (s, 2H), 5.80-5.86 (m, 2H), 5.94-5.96 (m, 2H), 6.53 (d, 1H), 6.66 (d, 1H), 6.89 (d, 1H), 7.00(t, 1H)
실시예 239: 1-(3-아미노-2-메틸-벤질)-4-[2-(5-에틸-퓨란-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.20 (t, 3H), 1.99 (s, 3H), 2.59 (q, 2H), 3.04 (t, 2H), 3.68 (br s, 2H), 4.14 (t, 2H), 5.04 (s, 2H), 5.80 (dd, 1H), 5.86 (d, 1H), 5.94 (d, 1H), 5.97 (d, 1H), 6.55 (d, 1H), 6.67 (d, 1H), 6.89 (d, 1H), 7.00 (t, 1H)
실시예 240: 5-[1-(3-아미노-2-메틸-벤질)-2-옥소-1,2-다이하이드로-피리딘-4-일옥시메틸]-퓨란-2-카복실산 에틸 에스터
1H NMR (CDCl3, 300 MHz) δ 1.37 (t, 3H), 2.00 (s, 3H), 4.36 (q, 2H), 4.97 (s, 2H), 5.05 (s, 2H), 5.84 (dd, 1H), 6.01 (d, 1H), 6.55-6.58 (m, 2H), 6.69 (d, 1H), 6.93 (d, 1H), 7.02 (t, 1H), 7.14 (d, 1H)
실시예 241: 1-[3-(2-다이메틸아미노-에틸아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 1.99 (s, 3H), 2.30 (s, 6H), 2.60 (t, 2H), 3.17 (t, 2H), 3.28 (t, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.88-6.96 (m, 3H), 7.09-7.18 (m, 2H)
실시예 242: 1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸설파닐-싸이오펜-2-일)-에톡 시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 2.01 (s, 3H), 2.45 (s, 3H), 3.21 (t, 2H), 3.70 (br s, 2H), 4.12 (t, 2H), 5.05 (s, 2H), 5.84 (dd, 1H), 5.93 (d, 1H), 6.57 (d, 1H), 6.69-6.73 (m, 2H), 6.91-6.93 (m, 2H), 7.02 (t, 1H)
실시예 243: 1-(3-아미노-2-메틸-벤질)-4-(2-벤조퓨란-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.05 (s, 3H), 3.25 (t, 2H), 4.29 (t, 2H), 5.05 (s, 2H), 5.82 (d, 1H), 6.00 (s, 1H), 6.51-6.71 (m, 3H), 6.91 (d, 1H), 7.04 (t, 1H), 7.17-7.28 (m, 2H), 7.42 (d, 1H), 7.50 (d, 1H)
실시예 244: 1-(3-아미노-2-메틸-벤질)-4-[2-(3-메틸-아이속사졸-5-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3 + 몇 방울의 CD3OD, 300 MHz) δ1.86 (s, 3H), 1.93 (s, 3H), 2.63 (t, 2H), 4.14 (t, 2H), 4.96 (s, 2H), 5.82 (dd, 1H), 5.90 (d, 1H), 6.46 (d, 1H), 6.64 (d, 1H), 6.86 (d, 1H), 6.94 (t, 1H), 7.26 (s, 1H)
실시예 245: 1-(3-아미노-2-메틸-벤질)-4-[2-(4,5-다이메틸-싸이오펜-2-일)-에톡 시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.00 (s, 3H), 2.07 (s, 3H), 2.78 (s, 3H), 3.14 (t, 2H), 4.09 (t, 2H), 5.05 (s, 2H), 5.85 (dd, 1H), 5.95 (d, 1H), 6.55 (s, 1H), 6.56 (d, 1H), 6.69 (d, 1H), 6.91 (d, 1H), 7.01 (t, 1H)
실시예 246: 1-(3-아미노-2-메틸-벤질)-4-[2-(5-에틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.28 (t, 3H), 2.00 (s, 3H), 2.78 (q, 2H), 3.20 (t, 2H), 3.69 (br s, 2H), 4.11 (t, 2H), 5.04 (s, 2H), 5.84 (dd, 1H), 5.94 (d, 1H), 6.55-6.70 (m, 4H), 6.91 (d, 1H), 7.01 (t, 1H)
실시예 247: 1-(3-아미노-2,6-다이클로로-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 3.25 (t, 2H), 4.12 (t, 2H), 4.30 (br s, 2H), 5.30 (s, 2H), 5.81 (dd, 1H), 5.92 (d, 1H), 6.70-6.93 (m, 4H), 7.13-7.16 (m, 2H)
실시예 248: N-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐}-아세트아마이드
1H NMR (DMSO-d 6 , 300 MHz) δ 2.02 (s, 3H), 2.08 (s, 3H), 3.22 (t, 2H), 4.17 (t, 2H), 5.00 (s, 2H), 5.87 (d, 1H), 5.99 (dd, 1H), 6.57 (d, 1H), 6.94-6.96 (m, 2H), 7.07 (t, 1H), 7.19 (d, 1H), 7.32-7.34 (m, 1H), 7.43 (d, 1H)
실시예 249: 1-[2-메틸-3-(2-피페리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.59 (br s, 2H), 1.83-1.87 (m, 4H), 2.07 (s, 3H), 2.90-2.94 (m, 4H), 3.06 (t, 2H), 3.28 (t, 2H), 3.52 (t, 2H), 4.13 (t, 2H), 4.60 (br s, 1H), 5.03 (s, 2H), 5.86 (dd, 1H), 5.92 (d, 1H), 6.46 (d, 1H), 6.59 (d, 1H), 6.88-6.96 (m, 3H), 7.07 (t, 1H), 7.16 (dd, 1H)
실시예 250: 1-[2-메틸-3-(2-모폴린-4-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.00 (s, 3H), 2.47 (t, 4H), 2.69 (t, 2H), 3.18 (t, 2H), 3.28 (t, 2H), 3.70 (t, 4H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.53 (d, 1H), 6.61 (d, 1H), 6.88-6.95 (m, 3H), 7.10 (d, 1H), 7.15 (t, 1H)
실시예 251: N-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐}-메탄설폰아마이드
1H NMR (CDCl3, 300 MHz) δ 2.15 (s, 3H), 2.95 (s, 3H), 3.30 (t, 2H), 4.17 (t, 2H), 5.01 (s, 2H), 5.97 (dd, 2H), 6.03 (d, 1H), 6.74 (d, 1H), 6.89-6.96 (m, 2H), 7.01 (d, 1H), 7.09 (t, 1H), 7.16 (dd, 1H), 7.28 (t, 1H), 7.60 (br s, 1H)
실시예 252: 1-(3-아미노-2-메틸-벤질)-4-[2-(4-브로모-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.99 (s, 3H), 3.22 (t, 2H), 3.69 (br s, 2H), 4.10 (t, 2H), 5.04 (s, 2H), 5.83 (dd, 1H), 5.92 (d, 1H), 6.55 (d, 1H), 6.68 (d, 1H), 6.80 (s, 1H), 6.91 (d, 1H), 6.98-7.06 (m, 2H)
실시예 253: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ4.15 (t, 2H), 4.25 (t, 2H), 5.07 (s, 2H), 5.85-5.90 (m, 2H), 5.94 (s, 2H), 6.15-6.16 (m, 2H), 6.60-6.72 (m, 2H), 6.79 (s, 1H), 6.83 (s, 1H), 7.18 (d, 1H)
실시예 254: 1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ3.26 (t, 2H), 4.12 (t, 2H), 5.06 (s, 2H), 5.89-5.92 (m, 4H), 6.78-6.94 (m, 4H), 7.14-7.18 (m, 2H)
실시예 255: 1-[2-메틸-3-(2-피롤리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.78 (br s, 4H), 1.98 (s, 3H), 2.55 (br s, 4H), 2.79 (t, 2H), 3.23 (t, 2H), 3.28 (t, 2H), 4.14 (t, 2H), 4.33 (br s, 1H), 5.05 (s, 2H), 5.81-5.85 (m, 1H), 5.94 (d, 1H), 6.53 (d, 1H), 6.63 (d, 1H), 6.88-6.96 (m, 3H), 7.09-7.18 (m, 2H)
실시예 256: N-(2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-에틸)-아세트아마이드
1H NMR (CDCl3, 300 MHz) δ 1.94 (s, 6H), 3.25 (t, 4H), 3.49 (q, 2H), 4.10 (t, 2H), 5.00 (s, 2H), 5.83-5.89 (m, 2H), 6.44 (d, 1H), 6.58 (d, 1H), 6.73 (t, 1H), 6.87-6.94 (m, 3H), 7.06 (t, 1H), 7.14 (d, 1H)
실시예 257: 1-{2-메틸-3-[(피리딘-3-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.03 (s, 3H), 3.28 (t, 2H), 4.14 (t, 2H), 4.42 (s, 2H), 5.07 (s, 2H), 5.86 (dd, 1H), 5.93 (d, 1H), 6.56 (d, 2H), 6.88-6.96 (m, 3H), 7.07 (t, 1H), 7.16 (dd, 1H), 7.30-7.34 (m, 1H), 7.73 (d, 1H), 8.54 (s, 1H), 8.64 (s, 1H)
실시예 258: 2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐 에스터
1H NMR (CDCl3, 300 MHz) δ2.26 (s, 3H), 3.16 (s, 3H), 3.27 (t, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.93-5.95 (m, 2H), 6.88-7.00 (m, 4H), 7.14-7.26 (m, 3H)
실시예 259: 1-{2-메틸-3-[(피리딘-4-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.07 (s, 3H), 3.28 (t, 2H), 4.14 (t, 2H), 4.44 (s, 2H), 5.08 (s, 2H), 5.86 (dd, 1H), 5.94 (d, 1H), 6.42 (d, 2H), 6.54 (d, 1H), 6.88-7.11 (m, 4H), 7.16 (dd, 1H), 7.30 (d, 2H), 8.55 (d, 2H)
실시예 260: 1-{2-메틸-3-[(싸이아졸-4-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ2.04 (s, 3H), 3.28 (t, 2H), 4.14 (t, 2H), 4.56 (s, 2H), 5.06 (s, 2H), 5.84 (dd, 1H), 5.94 (d, 1H), 6.55 (d, 1H), 6.65 (d, 1H), 6.88-7.20 (m, 6H), 8.85 (s, 1H)
실시예 261: 1-[3-(4-메톡시-벤질옥시)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ 2.15 (s, 3H), 3.29 (t, 2H), 3.81 (s, 3H), 4.16 (t, 2H), 4.99 (s, 2H), 5.08 (s, 2H), 5.88 (dd, 1H), 6.00 (d, 1H), 6.68 (d, 1H), 6.90-6.96 (m, 6H), 7.11-7.18 (m, 2H), 7.35 (d, 2H)
실시예 262: 1-{3-[(3.5-다이메틸-아이속사졸-4-일메틸)-아미노]-2-메틸-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.98 (s, 3H), 2.26 (s, 3H), 2.37 (s, 3H), 3.28 (t, 2H), 4.04 (s, 2H), 4.15 (t, 2H), 5.07 (s, 2H), 5.85-5.95 (m, 2H), 6.62 (d, 1H), 6.74 (d, 1H), 6.88-6.96 (m, 3H), 7.14-7.19 (m, 2H)
실시예 263: 1-(3-하이드록시-2-메틸-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3 + 몇 방울의 CD3OD, 300 MHz) δ 1.96 (s, 3H), 3.16 (t, 2H), 4.05 (t, 2H), 4.91 (s, 2H), 5.85-5.88 (m, 2H), 6.41 (d, 1H), 6.66 (d, 1H), 6.76-6.90 (m, 4H), 7.04 (d, 1H)
실시예 264: 1-{2-메틸-3-[(1-메틸-피롤리딘-2-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3 + 몇 방울의 CD3OD, 300 MHz) δ 1.57-1.67 (m, 3H), 1.79-1.89 (m, 6H), 2.25 (s, 3H), 2.47-2.50 (m, 1H), 2.98-3.04 (m, 2H), 3.13 (t, 2H), 4.01 (t, 2H), 4.88 (s, 2H), 5.78-5.81 (m, 2H), 6.32 (d, 1H), 6.47 (d, 1H), 6.73-6.85 (m, 3H), 6.94 (t, 1H), 7.00 (d, 1H)
실시예 265: 1-{2-메틸-3-[2-(1-메틸-피롤리딘-2-일)-에틸아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온
1H NMR (CDCl3, 300 MHz) δ1.67-1.79 (m, 3H), 1.90-1.98 (m, 6H), 2.24 (q, 2H), 2.40 (s, 3H), 3.10-3.30 (m, 5H), 4.14 (t, 2H), 4.88 (br s, 1H), 5.04 (s, 2H), 5.82 (dd, 1H), 5.93 (d, 1H), 6.52 (d, 1H), 6.60 (d, 1H), 6.88-6.96 (m, 3H), 7.08-7.17 (m, 2H)
실시예 266: (2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-에틸)-포스폰산 다이에틸 에스터
1H NMR (CDCl3, 300 MHz) δ1.32 (t, 6H), 2.02 (s, 3H), 2.10-2.20 (m, 2H), 3.28 (t, 2H), 3.42-3.53 (m, 2H), 4.07-4.17 (m, 6H), 5.06 (s, 2H), 5.85 (dd, 1H), 5.96 (s, 1H), 6.57 (d, 1H), 6.68 (d, 1H), 6.88-6.96 (m, 3H), 7.10-7.17 (m, 2H)
4-(아이소부틸싸이오)피리딘 1-옥사이드의 제조: 30ml의 DMF 중의 5.80g의 아이소부틸싸이올을 상온에서 교반하고 2.55g의 NaOMe를 첨가하였다. 30분 후에 6.0g의 N-옥사이드를 첨가하고 반응 혼합물을 환류에서 15시간 동안 가열하였다. 혼합물을 냉각시키고 나서, 용액을 증발시키고, 다이클로로메탄을 이용하여 추출한 후, 실리카 겔 컬럼 크로마토그래피(헥산/에틸 아세테이트)에 가하여 5.8g의 4-(아이소부틸싸이오)피리딘 1-옥사이드를 수득하였다.
1H NMR (CDCl3, 300 MHz) δ0.99(s, 3H), 1.01(s, 3H), 1.85-1.89(m, 1H), 2.78(d, J=6.9Hz, 2H), 7.04(d, J=7.2Hz, 2H), 8.01(d, J=7.5Hz, 2H)
4-(아이소부틸싸이오)피리딘-2(1 H )-온의 제조: 500mg의 4-(아이소부틸싸이 오)피리딘-N-옥사이드, 5ml의 무수아세트산의 혼합물을 10시간 동안 환류하며 가열시켰다. 혼합물을 냉각시키고 나서, MeOH를 첨가하고 pH 9 내지 11이 되도록 3N NaOH를 한 방울씩 첨가하고 교반하였다. 1시간 후에 용액을 증발시키고, pH 6.5 내지 7.5가 되도록 3N HCl을 한 방울씩 첨가하고, 에틸 아세테이트를 이용하여 추출한 후, 실리카 겔 컬럼 크로마토그래피(헥산/에틸 아세테이트)에 가하여 상기 화합물(90mg)을 수득하였다.
1H NMR (CDCl3, 300 MHz) δ1.05(s, 3H), 1.07(s, 3H), 1.95-2.00(m, 1H), 2.79(d, J=6.9Hz, 2H), 6.19(dd, 1H), 6.31(s, 1H), 7.21(d, J=6.9Hz, 1H)
실시예 267: 4-(아이소부틸싸이오)-1-(2-메틸-3-나이트로벤질)피리딘-2(1H)-온
4-(아이소부틸싸이오)-1-(2-메틸-3-나이트로벤질)피리딘-2(1 H )-온의 제조: 100mg의 4-(아이소부틸싸이오)피리딘-2(1H)-온, 2ml의 DMF, 65mg의 t-BuOK의 혼합물을 상온에서 교반하고, 105mg의 2-메틸-3-나이트로벤질 클로라이드를 첨가하였다. 3시간 후에, 생성 용액을 증발시키고, 다이클로로메탄을 이용하여 추출한 후, 실리카 겔 컬럼 크로마토그래피(헥산/에틸 아세테이트)에 가하여 화합물(90mg)을 수득하였다.
1H NMR (CDCl3, 300 MHz) δ1.06(s, 3H), 1.08(s, 3H), 1.94-2.03(m, 1H), 2.42(s, 3H), 2.80(, J=6.9Hz, 2H), 5.15(s, 2H), 6.07(dd, 1H), 6.35(s, 1H), 6.93(, J=7.5Hz, 1H), 7.19-7.33(m, 2H), 7.71(, J=8.1Hz, 1H)
실시예 268 내지 280: 출발 물질을 제외하고는 실시예 267의 과정을 반복하여 표제 화합물을 수득하였다.
실시예 268: 1-(3-아미노-2-메틸벤질)-4-(아이소부틸싸이오)피리딘-2(1H)-온
400mg의 1-(3-아미노-2-메틸벤질)-4-(아이소부틸싸이오)피리딘-2(1H)-온, 5ml의 에틸 알코올, 물 중의 3ml의 라니 니켈(Raney nickel)의 혼합물을 상온에서 교반하고, 3.5ml의 NH2NH2H2O를 한 방울씩 첨가하였다. 1시간 후에, 셀라이트(Celite)를 이용하여 여과함으로써 촉매를 제거하고, 생성 용액을 증발시켜서, 다이클로로메탄을 이용하여 추출해서 표제 화합물(200mg)을 수득하였다.
1H NMR (CDCl3, 300 MHz) δ1.01-1.07(m, 6H), 1.95-1.99(m, 1H), 2.13(s, 3H), 2.77(d, J=6.9Hz, 2H), 5.07(s, 2H), 5.97(dd, 1H), 6.32(s, 1H), 6.70(d, J=7.8Hz, 1H), 6.85-6.92(m, 2H), 7.08(t, J=7.8Hz, 1H)
실시예 269: 1-(3-아미노-2-메틸벤질)-4-(퓨란-2-일메틸싸이오)피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ2.03(s,3H), 4.14(s,2H), 5.05(s,2H), 5.96(dd, 1H), 6.31(s, 2H), 6.45(d, J=7.8Hz, 1H), 6.76(d, J=7.5Hz, 1H), 6.88(d, J=6.9Hz, 1H), 7.04(t, J=7.8Hz, 1H), 7.36(s, 1H)
실시예 270: 1-(3-아미노-2-메틸벤질)-4-(펜틸싸이오)피리딘-2-(1H)-온
1H NMR (CDCl3, 300 MHz) δ0.89-0.93(m, 3H), 1.31-1.44(m, 4H), 1.66-1.73(m, 2H), 2.03(s, 3H), 2.85-2.90(m, 2H), 5.05(s, 2H), 5.92-5.95(m, 1H), 6.33(s, 1H), 6.60(d, J=7.2Hz, 1H), 6.73(d, J=7.8Hz, 1H), 6.85(q, 1H), 7.03(t, J=7.8Hz, 1H)
실시예 271: 1-(3-아미노-2-메틸벤질)-4-(페네틸싸이오)피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ2.13(s, 3H), 3.00(t, J=7.5Hz, 2H), 3.16(t, J=7.5Hz, 2H), 5.06(s, 2H), 5.94-5.97(dd, 1H), 6.39(s, 1H), 6.66(bs, 1H), 6.88(d, J=7.5Hz, 2H), 7.06-7.10(m, 1H), 7.19-7.35(m, 3H)
실시예 272: 1-(3-아미노-2-메틸벤질)-4-(부틸싸이오)피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ0.95(t, J=7.2Hz, 3H), 1.43-1.50(m,2H), 1.67-1.72(m,2H), 2.04(s, 3H), 2.89(t, J=7.3Hz, 2H), 5.05(s, 2H), 5.94(dd, 1H), 6.33(s, 1H), 6.61(d, J=7.6Hz, 1H), 6.75(d, J=8.1Hz, 1H), 6.86(d, J=7.2Hz, 1H), 7.04(t, J=7.6Hz, 1H)
실시예 273: 1-(3-아미노-2-메틸벤질)-4-(싸이오펜-2-일메틸싸이오)피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ2.03(s, 3H), 4.34(s,2H), 5.04(s, 2H), 5.95(dd, 1H), 6.41(bs, 1H), 6.60(d, J=7.5Hz, 1H), 6.75(d, J=7.5Hz, 1H), 6.87-6.95(m, 2H), 7.01-7.05(m, 2H), 7.21-7.26(m, 1H)
실시예 274: 1-(3-아미노-2-메틸벤질)-4-(펜틸싸이오)피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ0.92(t, J=6.8Hz, 3H), 1.32-1.46(m, 4H), 1.68-1.78(m, 2H), 2.43(s, 3H), 2.91(t, J=7.3Hz, 2H), 5.15(s, 2H), 6.07(dd, 1H), 6.38-6.39(m, 1H), 6.94(d, J=7.2Hz, 1H), 7.20-7.31(m, 2H), 7.72(d, J=8.1Hz, 2H)
실시예 275: 1-(3-아미노-2-메틸벤질)-4-(프로필싸이오)피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ1.05(t, J=7.5Hz, 3H), 1.71-1.78(m, 2H), 2.02(s, 3H), 2.87(t, J=7.3Hz, 2H), 5.06(s, 2H), 5.94(dd, 1H), 6.33(d, J=1.8Hz, 1H), 6.59(d, J=7.8Hz, 1H), 6.70(d, J=7.5Hz, 1H), 6.86(d, J=7.2Hz, 1H), 7.03(t, J=7.8Hz, 1H)
실시예 276: 1-(3-아미노-2-메틸벤질)-4-(1-메틸부틸싸이오)피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ0.93-1.02(m, 6H), 1.55-1.62(m, 2H), 1.68-1.75(m, 1H), 2.06(s, 3H), 2.89(t, J=7.5Hz, 2H), 5.06(s, 2H), 5.94(dd, 1H), 6.33(s, 1H), 6.63(d, J=7.2Hz, 1H), 6.78(d, J=8.1Hz, 1H), 6.86(d, J=7.2Hz, 1H), 7.04(t, J=7.6Hz, 1H)
실시예 277: N,N-다이메틸-3-(2-메틸-3-((2-옥소-4-(2-(싸이오펜-2-일)에톡시)피리딘-1(2H)-일)메틸)페닐아미노)프로판-1-설폰아마이드
1H NMR (CDCl3, 300 MHz) δ2.06(s, 3H), 2.23(t, J=6.8Hz, 2H), 2.87(s, 6H), 3.06(t, J=7.2Hz, 2H), 3.29(t, J=6.5Hz, 2H), 3.39(t, J=6.7Hz, 2H), 3.62-3.68(m, 1H), 4.14-4.18(m, 2H), 5.06(s, 2H), 5.87(dd, 1H), 5.97(d, J=2.1Hz, 1H), 6.60(d, J=7.5Hz, 1H), 6.80(bs, 1H), 6.90(bs, 1H), 6.93-6.96(m, 2H), 7.10-7.18(m, 2H)
실시예 278: 1-(3-나이트로-2-메틸벤질)-4-클로로피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ2.38(s, 3H), 5.38(s, 2H), 6.54(dd, 1H), 7.27(d, J=7.8Hz, 1H), 7.45(t, J=7.9Hz, 1H), 7.79(d, J=7.8Hz, 2H), 8.21(s, 1H)
실시예 279: 1-(3-아미노-2-메틸벤질)-4-클로로피리딘-2(1H)-온
1H NMR (CDCl3, 300 MHz) δ1.94(s, 3H), 5.08(s, 2H), 6.23-6.28(m, 2H), 6.63(d, J=7.8Hz, 1H), 6.90(t, J=7.8Hz, 1H), 8.11(s, 1H)
실시예 280: 1-(3-아미노-2-메틸벤질)-4-(2-(싸이오펜-2-일)에틸아미노)피리딘-2-(1H)-온
1H NMR (CDCl3, 300 MHz) δ2.02(s, 3H), 3.07(t, J=6.8Hz, 2H), 3.37(t, J=6.5Hz, 2H), 4.97(s, 2H), 5.64(d, J=8.1Hz, 2H), 6.55(d, J=7.5Hz, 1H), 6.75-6.83(m, 3H), 6.88-6.91(m, 1H), 7.00(t, J=7.5Hz, 1H), 7.12(d, J=5.1Hz, 1H)
실험예 1: 최소억제농도(Minimum Inhibitory Concentration, MIC)
표준 균주에 대한 MIC 값을 측정함으로써 실시예에서 합성한 화합물의 항균 활성을 평가하였다. 구체적으로, MIC 값은 하기의 단계를 수행함으로써 측정하였다: 2배 희석법에 따라 테스트 화합물을 희석하는 단계; 뮐러-힌톤 아가 브로스(Mㆌller-Hinton agar broth)에서 생성 희석액을 분산시키는 단계; 107 cfu(colony forming unit, 콜로니 형성 단위)/ml의 농도를 갖는 표준 균주 컬쳐 2ml를 접종하는 단계; 혼합물을 20시간 동안 37℃에서 배양하는 단계. 측정 결과, MIC 값은 128 내지 0.2㎍/ml의 범위였고, 바람직하게는, 1 내지 0.2㎍/ml의 범위였다. 이러 한 결과는 본 발명의 화합물이 MRSA 균주를 포함한 다양한 감염성 박테리아 균주에 대한 우수한 항균 활성을 갖는다는 것을 나타낸다.

Claims (27)

  1. 하기 화학식 I의 화학식을 갖는 화합물, 또는 이의 약학적으로 허용가능한 염:
    화학식 I
    Figure 112014068294121-pct00014
    상기 식에서,
    R1은 치환된 C2-8 알킬이고;
    상기 치환된 C2-8 알킬은 C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, 고리구조에서 N, S 및 O로 이루어진 군에서 선택되는 하나 이상의 헤테로원자를 함유하는 5원, 6원 및 9원의 헤테로아릴, 및 고리구조에서 N, S 및 O로 이루어진 군에서 선택되는 하나 이상의 헤테로원자를 함유하는 5원, 6원 및 9원의 치환된 헤테로아릴로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유하고,
    여기서, 상기 고리구조에서 N, S 및 O로 이루어진 군에서 선택되는 하나 이상의 헤테로원자를 함유하는 5원, 6원 및 9원의 치환된 헤테로아릴은 각각 독립적으로 C1-6 알킬, C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, C1-6 알킬옥시, 아미노, C1-6 알킬아미노, 카복실, 나이트로, 설포닐아마이드, C1-6 알킬설포닐, 아마이드, 다이옥소아이소인돌, 트라이할로C1-6 알킬 및 C5-10 아릴로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유하고;
    A는 CH이고;
    B는 CH2이고;
    R4는 치환된 C5-10 아릴이고;
    상기 치환된 C5-10 아릴은 하이드록실, 할로겐, C1-6 알킬, C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, C1-6 알킬옥시, 아미노, C1-6 알킬아미노, 카복실, 나이트로, 설포닐아마이드, C1-6 알킬설포닐, 아마이드, 다이옥소아이소인돌, 트라이할로C1-6 알킬, C5-10 아릴, 고리구조에서 N, S 및 O로 이루어진 군에서 선택되는 하나 이상의 헤테로원자를 함유하는 5원, 6원 및 9원의 헤테로아릴, 치환된 C5-10 아릴 및 고리구조에서 N, S 및 O로 이루어진 군에서 선택되는 하나 이상의 헤테로원자를 함유하는 5원, 6원 및 9원의 치환된 헤테로아릴로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유하고,
    여기서, 상기 치환된 C5-10 아릴, 및 고리구조에서 N, S 및 O로 이루어진 군에서 선택되는 하나 이상의 헤테로원자를 함유하는 5원, 6원 및 9원의 치환된 헤테로아릴은 각각 독립적으로 C1-6 알킬, C3-8 사이클로알킬, C3-8 헤테로사이클로알킬, C1-6 알킬옥시, 아미노, C1-6 알킬아미노, 카복실, 나이트로, 설포닐아마이드, C1-6 알킬설포닐, 아마이드, 다이옥소아이소인돌, 트라이할로C1-6 알킬 및 C5-10 아릴로 이루어진 그룹에서 선택된 하나 이상의 치환기를 함유하고;
    W는 CH이고;
    Z는 CH이고;
    X는 O이다.
  2. 제1항에 있어서,
    상기 R1의 C2-8 알킬 그룹이 선형인 것을 특징으로 하는 화합물.
  3. 제1항에 있어서,
    상기 R1의 C2-8 알킬 그룹이 분지형인 것을 특징으로 하는 화합물.
  4. 제1항에 있어서,
    상기 화합물은 하기로 이루어진 그룹에서 선택된 것을 특징으로 하는 화합물:
    1-(2,4-다이클로로-벤질)-4-(5-모폴린-4-일-펜틸옥시)-1H-피리딘-2-온;
    1-(2,4-다이클로로-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-(2,4-다이클로로-벤질)-4-(2-싸이오펜-3-일-에톡시)-1H-피리딘-2-온;
    1-(2,4-다이클로로-벤질)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온;
    1-(2,4-다이클로로-벤질)-4-(3-피롤-1-일-프로폭시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(4-메틸-싸이아졸-5-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-(2-(5-브로모싸이오펜-2-일)-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-(2-(5-플루오로싸이오펜-2-일)-에톡시)-1H-피리딘-2-온;
    1-[3-(2-하이드록시-에틸아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[3-(사이클로프로필메틸-아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[2-메틸-3-(2-피롤-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[2-메틸-3-(2-옥소-2-피롤리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[2-메틸-3-(2-옥소-2-피페리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-{2-메틸-3-[2-(4-메틸-피페라진-1-일)-2-옥소-에틸아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[2-메틸-3-(2-모폴린-4-일-2-옥소-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-(2-퓨란-2-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(5-클로로-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(2,4-다이클로로-벤질)-4-[2-(3-메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-(2-벤조[b]싸이오펜-3-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(5-클로로-3-메틸-벤조[b]싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(3-메틸-벤조[b]싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸-퓨란-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(5-에틸-퓨란-2-일)-에톡시]-1H-피리딘-2-온;
    1-[3-(2-다이메틸아미노-에틸아미노)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(5-메틸설파닐-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-(2-벤조퓨란-2-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(3-메틸-아이속사졸-5-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(4,5-다이메틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(5-에틸-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(3-아미노-2,6-다이클로로-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    N-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐}-아세트아마이드;
    1-[2-메틸-3-(2-피페리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[2-메틸-3-(2-모폴린-4-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-(3-아미노-2-메틸-벤질)-4-[2-(4-브로모-싸이오펜-2-일)-에톡시]-1H-피리딘-2-온;
    1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-피롤-1-일-에톡시)-1H-피리딘-2-온;
    1-(6-클로로-벤조[1,3]다이옥솔-5-일메틸)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[2-메틸-3-(2-피롤리딘-1-일-에틸아미노)-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    N-(2-{2-메틸-3-[2-옥소-4-(2-싸이오펜-2-일-에톡시)-2H-피리딘-1-일메틸]-페닐아미노}-에틸)-아세트아마이드;
    1-{2-메틸-3-[(피리딘-3-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-{2-메틸-3-[(피리딘-4-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-{2-메틸-3-[(싸이아졸-4-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-[3-(4-메톡시-벤질옥시)-2-메틸-벤질]-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-{3-[(3,5-다이메틸-아이속사졸-4-일메틸)-아미노]-2-메틸-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-(3-하이드록시-2-메틸-벤질)-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온;
    1-{2-메틸-3-[(1-메틸-피롤리딘-2-일메틸)-아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온; 및
    1-{2-메틸-3-[2-(1-메틸-피롤리딘-2-일)-에틸아미노]-벤질}-4-(2-싸이오펜-2-일-에톡시)-1H-피리딘-2-온.
  5. 삭제
  6. 삭제
  7. 삭제
  8. 삭제
  9. 삭제
  10. 삭제
  11. 삭제
  12. 삭제
  13. 삭제
  14. 삭제
  15. 삭제
  16. 삭제
  17. 삭제
  18. 삭제
  19. 삭제
  20. 삭제
  21. 삭제
  22. 삭제
  23. 삭제
  24. 삭제
  25. 삭제
  26. 삭제
  27. 삭제
KR1020087011392A 2005-10-13 2006-10-13 Ｆａｂ Ｉ 저해제 및 그의 제조 방법 KR101502335B1 (ko)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US72681405P 2005-10-13 2005-10-13
US60/726,814 2005-10-13
US82702906P 2006-09-26 2006-09-26
US60/827,029 2006-09-26
US11/548,349 2006-10-11
US11/548,349 US7973060B2 (en) 2005-10-13 2006-10-11 Fab I inhibitor and process for preparing same
PCT/KR2006/004133 WO2007043835A1 (en) 2005-10-13 2006-10-13 Fab i inhibitor and process for preparing same

Related Child Applications (1)

Application Number Title Priority Date Filing Date
KR1020147004300A Division KR101522713B1 (ko) 2005-10-13 2006-10-13 Ｆａｂ Ｉ 저해제 및 그의 제조 방법

Publications (2)

Publication Number Publication Date
KR20080068060A KR20080068060A (ko) 2008-07-22
KR101502335B1 true KR101502335B1 (ko) 2015-03-16

Family

ID=37943021

Family Applications (2)

Application Number Title Priority Date Filing Date
KR1020147004300A KR101522713B1 (ko) 2005-10-13 2006-10-13 Ｆａｂ Ｉ 저해제 및 그의 제조 방법
KR1020087011392A KR101502335B1 (ko) 2005-10-13 2006-10-13 Ｆａｂ Ｉ 저해제 및 그의 제조 방법

Family Applications Before (1)

Application Number Title Priority Date Filing Date
KR1020147004300A KR101522713B1 (ko) 2005-10-13 2006-10-13 Ｆａｂ Ｉ 저해제 및 그의 제조 방법

Country Status (9)

Country Link
US (1) US7973060B2 (ko)
EP (1) EP1948601B1 (ko)
JP (1) JP5049977B2 (ko)
KR (2) KR101522713B1 (ko)
CN (1) CN101282930B (ko)
BR (1) BRPI0617268A2 (ko)
CA (1) CA2625962C (ko)
ES (1) ES2576579T3 (ko)
WO (1) WO2007043835A1 (ko)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7973060B2 (en) * 2005-10-13 2011-07-05 Crystalgenomics, Inc. Fab I inhibitor and process for preparing same
SI2300013T1 (en) 2008-05-21 2018-03-30 Adriad Pharmacaceuticals, Inc. Phosphorus derivatives as kinase inhibitors
US9273077B2 (en) 2008-05-21 2016-03-01 Ariad Pharmaceuticals, Inc. Phosphorus derivatives as kinase inhibitors
WO2011057989A1 (en) 2009-11-11 2011-05-19 Basf Se Heterocyclic compounds having herbicidal action
EP2649050A4 (en) * 2010-12-06 2014-04-23 Glaxo Group Ltd LINKS
KR101080267B1 (ko) * 2011-01-19 2011-11-08 덕성여자대학교 산학협력단 흑진주 벼 유래의 신규 항산화 활성 화합물의 제조 방법, 및 이를 함유하는 식품 및 약제학적 조성물
EA201391626A1 (ru) 2011-05-04 2014-03-31 Ариад Фармасьютикалз, Инк. Соединения для ингибирования клеточной пролиферации в egfr-стимулированных типах рака
CN102267987A (zh) * 2011-06-14 2011-12-07 广东中科药物研究有限公司 一种含氟的新抗菌化合物
CA2842531C (en) 2011-08-10 2019-07-16 Janssen R&D Ireland Antibacterial piperidinyl substituted 3,4-dihydro-1h-[1,8]naphthyridinones
JO3611B1 (ar) 2011-08-10 2020-08-27 Janssen Sciences Ireland Uc سايكلو بنتا (سي (بيرول 4,3 ثاني هيدرو 1 hمستبدله [8,1] نافثيريدينونات مضادة للجراثيم
MX360856B (es) 2011-08-10 2018-11-20 Janssen Sciences Ireland Uc 3,4-dihidro-1h-[1,8]naftiridinosas sustituidas con homopiperidinilo antibacterianas.
JP6469567B2 (ja) 2012-05-05 2019-02-13 アリアド・ファーマシューティカルズ・インコーポレイテッド Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物
MX367309B (es) 2012-08-10 2019-08-14 Janssen Sciences Ireland Uc Nuevos compuestos antibacterianos.
WO2014023815A1 (en) 2012-08-10 2014-02-13 Janssen R&D Ireland New antibacterial compounds
PL2931716T3 (pl) * 2012-12-13 2017-04-28 Novartis Ag Pochodne pirydonu i ich zastosowanie w leczeniu gruźlicy
US9611283B1 (en) 2013-04-10 2017-04-04 Ariad Pharmaceuticals, Inc. Methods for inhibiting cell proliferation in ALK-driven cancers
JP6026024B2 (ja) 2013-06-27 2016-11-16 ファイザー・インク 複素芳香族化合物およびそのドーパミンｄ１リガンドとしての使用
EP3186242B1 (en) 2014-08-29 2021-10-06 Tes Pharma S.r.l. Inhibitors of alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase
WO2017049211A1 (en) 2015-09-17 2017-03-23 Micromidas, Inc. Oxidation chemistry on furan aldehydes
MX2018006217A (es) 2015-12-04 2018-08-01 Squibb Bristol Myers Co Agonistas del receptor de apelina y metodos de uso.
CN107903260B (zh) * 2017-11-20 2019-05-03 中国医药集团总公司四川抗菌素工业研究所 一种吲哚并二氢吡啶酮化合物及其晶型和制备方法
KR20200009744A (ko) * 2018-07-20 2020-01-30 크리스탈지노믹스(주) Fab I 저해제를 포함하는 경구투여용 약제학적 조성물 및 그 제조방법
KR20200090359A (ko) * 2019-01-21 2020-07-29 크리스탈지노믹스(주) Fab I 저해제를 포함하는 주사제용 조성물 및 그 제조방법
JP2023527315A (ja) 2020-05-22 2023-06-28 アリゴス セラピューティクス インコーポレイテッド Ｐｄ－ｌ１を標的とするための方法及び組成物
WO2024028365A1 (en) * 2022-08-02 2024-02-08 Liminal Biosciences Limited Substituted pyridone gpr84 antagonists and uses thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003068230A1 (en) * 2002-02-14 2003-08-21 Pharmacia Corporation Substituted pyridinones as modulators of p38 map kinase
WO2005018557A2 (en) * 2003-08-13 2005-03-03 Pharmacia Corporation Substituted pyridinones

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3146229A (en) 1962-10-29 1964-08-25 Sterling Drug Inc 2-sulfanilamido-4-phenoxy-1, 3, 5-triazine
US3853900A (en) 1973-09-14 1974-12-10 Searle & Co 4-benzyloxy-2 (1h)-pyridones
US4348518A (en) * 1974-05-05 1982-09-07 Hoffmann-La Roche Inc. Cephalosporins
US3923792A (en) * 1974-06-19 1975-12-02 Hoffmann La Roche Sulfacytosine derivatives
EP0183212B1 (en) * 1984-11-29 1990-06-20 Nissan Chemical Industries Ltd. Pyridazinone derivatives, preparation thereof, and insecticidal, acaricidal, nematicidal, fungicidal compositions
JPS63215673A (ja) * 1987-03-03 1988-09-08 Nissan Chem Ind Ltd ピリダジノン化合物および病害虫防除剤
US5278163A (en) 1989-05-17 1994-01-11 Nissan Chemical Industries, Ltd. Pyridazinone derivatives and compositions for controlling and/or preventing insect pests
JPH0881447A (ja) 1994-09-14 1996-03-26 Kureha Chem Ind Co Ltd ベンジルオキシピリミジン誘導体、その製造方法及び除草剤
US5851952A (en) 1997-11-07 1998-12-22 American Cyanamid Company Herbicidal thienyloxyazines
US5924819A (en) * 1998-01-23 1999-07-20 Caterpillar Paving Products Linkage mechanism for an extendable asphalt paver screed
JP4803935B2 (ja) 1999-10-08 2011-10-26 アフィニアム・ファーマシューティカルズ・インコーポレイテッド Ｆａｂｉ阻害剤
JP4667589B2 (ja) * 2000-12-07 2011-04-13 株式会社クラレ ２，４−ジヒドロキシピリジンの製造方法
US6801137B2 (en) 2001-04-23 2004-10-05 Cardionet, Inc. Bidirectional communication between a sensor unit and a monitor unit in patient monitoring
AU2003209321A1 (en) * 2002-01-18 2003-07-30 Pharmacia Corporation Substituted pyridazinones as inhibitors of p38
US7902203B2 (en) * 2002-11-01 2011-03-08 Abbott Laboratories, Inc. Anti-infective agents
US6930117B2 (en) 2002-11-09 2005-08-16 The Procter & Gamble Company N-alkyl-4-methyleneamino-3-hydroxy-2-pyridones
ES2518316T3 (es) 2002-12-06 2014-11-05 Debiopharm International Sa Compuestos heterocíclicos, métodos de fabricación de los mismos y su uso en terapia
US20070027190A1 (en) 2003-01-17 2007-02-01 Moir Donald T Antibacterial fab i inhibitors
WO2005007632A1 (en) * 2003-07-18 2005-01-27 Pharmacia Corporation Substituted pyridazinones as inhibitors of p38
US7973060B2 (en) * 2005-10-13 2011-07-05 Crystalgenomics, Inc. Fab I inhibitor and process for preparing same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003068230A1 (en) * 2002-02-14 2003-08-21 Pharmacia Corporation Substituted pyridinones as modulators of p38 map kinase
WO2005018557A2 (en) * 2003-08-13 2005-03-03 Pharmacia Corporation Substituted pyridinones

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Organic Letters Vol. 5, No. 14, pp. 2441-2444 (2003) *
Tetrahedron Letters Vol. 46, pp. 7917-7920 (Epub. 2005. 10. 4.) *

Also Published As

Publication number Publication date
KR20080068060A (ko) 2008-07-22
JP5049977B2 (ja) 2012-10-17
US20070135465A1 (en) 2007-06-14
CN101282930B (zh) 2012-10-24
CA2625962C (en) 2014-11-04
JP2009511575A (ja) 2009-03-19
CN101282930A (zh) 2008-10-08
US7973060B2 (en) 2011-07-05
EP1948601B1 (en) 2016-04-13
EP1948601A1 (en) 2008-07-30
WO2007043835A1 (en) 2007-04-19
EP1948601A4 (en) 2011-04-06
KR101522713B1 (ko) 2015-05-26
CA2625962A1 (en) 2007-04-19
ES2576579T3 (es) 2016-07-08
KR20140029550A (ko) 2014-03-10
BRPI0617268A2 (pt) 2011-07-19

Similar Documents

Publication Publication Date Title
KR101502335B1 (ko) Ｆａｂ Ｉ 저해제 및 그의 제조 방법
EP1400518B1 (en) Heterocyclic compound derivatives and medicines
KR100518142B1 (ko) 혈당저하 및 지질혈저하 활성을 갖는 5-원ｎ-헤테로고리형 화합물
US8664401B2 (en) N-linked hydroxamic acid derivatives useful as antibacterial agents
EP2613785B1 (en) Heteroarylmethyl amides
US20060148858A1 (en) 1, 2-Azole derivatives with hypoglycemic and hypolipidemic activity
MX2013010276A (es) Derivados de fluoro-piridinona utiles como agentes antibacterianos.
US8669254B2 (en) Pyridine, pyridazine, pyrimidine or pyrazine carboxamides as HDL-cholesterol raising agents
JPH10509182A (ja) 新規なスルホンアミド類
EP2308838B1 (en) Nitrogen-containing aromatic heterocyclyl compound
JP2015504067A (ja) Ｎ−アミノスルホニルベンズアミド
CN104125960A (zh) 氮杂金刚烷的衍生物及其用途
RU2235095C2 (ru) 2,3-дизамещенное производное пиридина, способы его получения, содержащая его фармацевтическая композиция и промежуточный продукт для его получения
WO2004000813A1 (ja) フェノキシピリジン誘導体又はその塩
JPWO2002057237A1 (ja) 置換アミノ基を有するヘテロ３環化合物
JP2020520388A (ja) Ｌｄｈａ活性阻害剤
JP6703778B2 (ja) オートタキシン阻害活性を有する５位カルボニルアミノアルキル置換縮合ピラゾール誘導体
WO2008061399A1 (fr) Inhibiteur de synthase d'acide gras et utilisation
JP2020532507A (ja) Ｔｔｘ−ｓ遮断薬としてのビアリールオキシ誘導体
KR20130069857A (ko) N-피리딘-3-일 또는 n-피라진-2-일 카복스아마이드
JP7427665B2 (ja) 関節損傷を治療するための軟骨形成を誘導するための６－ヒドロキシ－８－オキサトリシクロ［３．２．１．０２，４］オクタン－２－カルボキサミド誘導体
KR20140092696A (ko) 신규의 페닐에티닐 벤즈아마이드 글루코키나제 활성화제 및 그의 제조방법

Legal Events

Date Code Title Description
A201 Request for examination
AMND Amendment
E902 Notification of reason for refusal
AMND Amendment
E601 Decision to refuse application
J201 Request for trial against refusal decision
A107 Divisional application of patent
AMND Amendment
E902 Notification of reason for refusal
B701 Decision to grant
GRNT Written decision to grant
FPAY Annual fee payment

Payment date: 20180118

Year of fee payment: 4

FPAY Annual fee payment

Payment date: 20190110

Year of fee payment: 5