JP5624148B2 - 大環状インテグラーゼ阻害剤 - Google Patents
大環状インテグラーゼ阻害剤 Download PDFInfo
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- 0 CC(C)(C)OC(NCc(cc1)c(***C(c(nc2C(OC)=O)c(cccn3)c3c2O*)=C)cc1F)=O Chemical compound CC(C)(C)OC(NCc(cc1)c(***C(c(nc2C(OC)=O)c(cccn3)c3c2O*)=C)cc1F)=O 0.000 description 9
- HCGWCDVMXRHFRQ-UHFFFAOYSA-N CC(C)(C)OC(NCCCCN(CC1)CCN1c(nc1C(OC)=O)c(cccn2)c2c1OCc1ccccc1)=O Chemical compound CC(C)(C)OC(NCCCCN(CC1)CCN1c(nc1C(OC)=O)c(cccn2)c2c1OCc1ccccc1)=O HCGWCDVMXRHFRQ-UHFFFAOYSA-N 0.000 description 1
- DMRJMORGJFLEAM-UHFFFAOYSA-N CC(C)(C)OC(NCCCCS(N(C)c(nc1C(OC)=O)c(cccn2)c2c1OS(c1ccc(C)cc1)(=O)=O)(=O)=O)=O Chemical compound CC(C)(C)OC(NCCCCS(N(C)c(nc1C(OC)=O)c(cccn2)c2c1OS(c1ccc(C)cc1)(=O)=O)(=O)=O)=O DMRJMORGJFLEAM-UHFFFAOYSA-N 0.000 description 1
- BAXWUMUEBGHDAK-UHFFFAOYSA-N CC(C)(C)OC(NCc(c(OCCCCCS(NC)(=O)=O)c1)ccc1F)=O Chemical compound CC(C)(C)OC(NCc(c(OCCCCCS(NC)(=O)=O)c1)ccc1F)=O BAXWUMUEBGHDAK-UHFFFAOYSA-N 0.000 description 1
- CXHDIWBVQMTALL-UHFFFAOYSA-N CC(C)(C)OC(NCc(ccc(F)c1)c1OCCCCC(O)=O)=O Chemical compound CC(C)(C)OC(NCc(ccc(F)c1)c1OCCCCC(O)=O)=O CXHDIWBVQMTALL-UHFFFAOYSA-N 0.000 description 1
- QIUGUPJNRFKBRL-UHFFFAOYSA-N CN(c(c1c2nccc1)nc(C(NCc(c(C(O)=O)c1)ccc1F)=O)c2O)SCCCCCN Chemical compound CN(c(c1c2nccc1)nc(C(NCc(c(C(O)=O)c1)ccc1F)=O)c2O)SCCCCCN QIUGUPJNRFKBRL-UHFFFAOYSA-N 0.000 description 1
- OUKBAQRKKLAPRM-UHFFFAOYSA-N COC(c(nc(c1cccnc11)Br)c1OCc1ccccc1)=O Chemical compound COC(c(nc(c1cccnc11)Br)c1OCc1ccccc1)=O OUKBAQRKKLAPRM-UHFFFAOYSA-N 0.000 description 1
- BMOIPJSBUTWBJH-UHFFFAOYSA-N O=C(CCCCOc1c(CNC(c2n3)=O)ccc(F)c1)N(CC1)CCN1c3c(cccn1)c1c2OCc1ccccc1 Chemical compound O=C(CCCCOc1c(CNC(c2n3)=O)ccc(F)c1)N(CC1)CCN1c3c(cccn1)c1c2OCc1ccccc1 BMOIPJSBUTWBJH-UHFFFAOYSA-N 0.000 description 1
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/18—Bridged systems
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
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- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D515/18—Bridged systems
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Description
Wは、−NH−、−N(CH3)−またはピペラジンであり、
Xは、結合、−C(=O)−または−S(=O)2−であり、
Yは、C3−7アルキレンであり、
Zは、−NH−C(=O)−または−O−である]
およびその医薬的に許容可能な塩に関する。分子断片または基において使用されるときはいつでも、点線−−−は、断片または基が分子の残余物と結合していることを表している。
式中、Wは、−NH−または−N(CH3)−であり、あるいは、
式中、Xは、結合または−S(=O)2−であり、あるいは、
式中、Yは、C4−5アルキレンであり、あるいは、
式中、Wがピペラジンの場合、Xは、−C(=O)−であり、かつ、Yは、C3−4アルキルであり、あるいは、
式中、Zは、−O−であり、あるいは、
式中、特に−NH−C(=O)−の窒素がYに結合される場合、Zは、−NH−C(=O)−であり、あるいは、
式中、−W−X−Y−Z−リンカーは、8または9個の原子長であり、あるいは、
式中、−W−X−Y−Z−は、
−−−NH−C5−7アルキレン−NH−C(=O)−−−、
−−−N(CH3)−S(=O)2−C4−5アルキレン−NH−C(=O)−−−、
−−−N(CH3)−S(=O)2−C4−5アルキレン−O−−−、
本発明に係る化合物は、各工程が当業者にとって既知である一連の工程により一般的に調製できる。特に、この特許出願における化合物は、1つ以上の以下の調製方法に従って調製できる。以下のスキームにおいて、他に示されない限り、使用される全ての可変物は、式(I)の化合物について定義するものである。
実施例1 メチル8−(ベンジルオキシ)−5−ブロモ−1,6−ナフチリジン−7−カルボキシレート
アセトン(600 ml)中の
1H NMR(400MHz,DMSO−d6)δppm1.25−1.65(m,8H)3.44(br.s.,4H)4.70(d,J=5.3Hz,2H)7.58(br.s.,1H)7.36(t,J=7.3Hz,1H)7.59(t,J=6.5Hz,1H)7.64(d,J=9.0Hz,1H)7.81(br.s.,1H)8.73(t,J=5.3Hz,1H)8.90(d,J=7.2Hz,1H)9.05(br.s.,1H)9.48(t,J=5.3Hz,1H)12.48(br.s.,1H)。
1H NMR(400MHz,DMSO−d6)δppm1.98(br.s.,2H)3.34(br.s.,2H)3.40(br.s.,2H)4.78(d,J=4.5Hz,2H)7.31(t,J=7.5Hz,1H)7.39(d,J=8.6Hz,1H)7.55(t,J=6.3Hz,1H)7.69(dd,J=7.2,3.7Hz,1H)7.73(br.s.,1H)8.56−8.72(m,2H)9.03(d,J=3.7Hz,1H)9.10(t,J=5.5Hz,1H)11.69(br.s.,1H)。
1H NMR(400MHz,DMSO−d6)δppm1.45(br.s.,4H)1.64−1.76(qt,J=5.7Hz,2H)3.34(q,J=5.5Hz,2H)3.71(t,J=5.3Hz,2H)4.80(d,J=6.6Hz,2H)7.58(br.s.,1H)7.32(t,J=7.4Hz,1H)7.40(d,J=9.2Hz,1H)7.56(t,J=6.8Hz,1H)7.80(dd,J=7.4,4.3Hz,1H)8.62(t,J=5.5Hz,1H)8.87(t,J=6.6Hz,1H)8.91(d,J=7.4Hz,1H)9.05(d,J=4.3Hz,1H)12.13(br.s.,1H)。
1H NMR(400MHz,DMSO−d6)δppm1.70(quin,J=6.5Hz,2H)1.80(quin,J=7.5Hz,2H)3.30−3.35(m,2H)3.37(s,3H)3.52(br.s.,2H)4.74(d,J=5.6Hz,2H)7.28−7.35(m,2H)7.62(dd,J=8.1,5.8Hz,1H)7.89(dd,J=8.4,4.1Hz,1H)8.54(dd,J=8.4,1.1Hz,1H)8.59(t,J=5.2Hz,1H)8.94(t,J=5.6Hz,1H)9.17(dd,J=4.1,1.1Hz,1H)13.60(br.s.,1H)。
1H NMR(400MHz,DMSO−d6)δppm1.42(quin,J=6.6Hz,2H)1.52(quin,J=5.8Hz,2H)2.47(d,J=11.4Hz,2H)2.70(t,J=6.6Hz,2H)2.89(t,J=10.4Hz,2H)3.34−3.44(m,4H)3.70(d,J=12.7Hz,2H)4.79(d,J=6.3Hz,2H)7.39(td,J=8.3,2.5Hz,1H)7.64−7.72(m,3H)8.44(dd,J=8.4,1.1Hz,1H)8.59(t,J=5.6Hz,1H)9.00(t,J=6.3Hz,1H)9.05(dd,J=4.1,1.1Hz,1H)12.72(br.s.,1H)。
1H NMR(300MHz,DMSO−d6)δppm1.56−1.68(m,2H)2.43(d,J=11.0Hz,2H)2.63(br.s.,2H)2.79(t,J=11.0Hz,2H)3.36−3.55(m,4H)3.71(d,J=12.8Hz,2H)4.89(d,J=3.0Hz,2H)7.37(td,J=8.0,2.5Hz,1H)7.57−7.65(m,2H)7.70(dd,J=8.5,4.1Hz,1H)8.42(d,J=8.5Hz,1H)8.67−8.78(m,2H)9.05(d,J=4.1Hz,1H)11.28(br.s.,1H)。
1H NMR(400MHz,クロロホルム−d)δppm1.75−1.86(m,1H)2.02−2.24(m,3H)2.33−2.39(m,1H)2.77−2.89(m,2H)3.07(dt,J=11.9,2.8Hz,1H)3.13−3.25(m,2H)3.61−3.69(m,1H)3.76−3.84(m,1H)3.97−4.04(m,1H)4.10−4.16(m,1H)4.18−4.24(m,1H)4.53(dd,J=14.2,6.8Hz,1H)4.59−4.65(m,1H)4.67(dd,J=14.2,6.8Hz,1H)6.61−6.67(m,2H)7.32(t,J=7.2Hz,1H)7.61(dd,J=8.4,4.2Hz,1H)8.60(dd,J=8.4,1.6Hz,1H)8.67(t,J=6.8Hz,1H)9.13(dd,J=4.2,1.6Hz,1 H)12.82(s,1H)。
1H NMR(400MHz,クロロホルム−d)δppm2.04(br.s.,2H)2.46(br.s.,2H)3.38−3.45(m,5H)4.08(br.s.,2H)4.61(d,J=5.5Hz,2H)6.59−6.72(m,2H)7.34(t,J=7.0Hz,1H)7.70(dd,J=8.0,4.3Hz,1H)8.63(d,J=8.0Hz,2H)9.18(br.s.,1H)13.33(s,1H)。
1H NMR(400MHz,クロロホルム−d)δppm1.83(quin,J=7.2Hz,2H)2.05(quin,J=5.7Hz,2H)2.21(br.s.,2H)3.31(t,J=8.0Hz,2H)3.41(s,3H)4.19(t,J=4.8Hz,2 H)4.66(d,J=6.0Hz,2H)6.63−6.73(m,2H)7.34(t,J=7.1Hz,1H)7.69(dd,J=8.3,4.0Hz,1H)8.29(t,J=6.0Hz,1H)8.63(d,J=8.3Hz,1H)9.18(d,J=4.0Hz,1H)13.58(s,1H)。
アッセイ1 HIV複製野生型、N155H変異体、およびQ148R変異体に対する阻害活性
MT4−LTR−高感度緑色蛍光タンパク質(EGFP)細胞を、EGFPを発現するためのプロモーターとしてHIV LTRについてのコード配列を含む選択可能な構築物でMT4細胞をトランスフェクトし、その後、永続的にトランスフェクトした細胞の選択によって得た。MT4−サイトメガロウイルス(CMV)−EGFP細胞を、CMV−EGFPレポーター遺伝子を有する永続的にトランスフェクトしたMT4細胞についての選択によって得た。細胞株を、10%の熱で不活性化したウシ胎仔血清、2mMのL−グルタミン、0.1%NaHCO3、および抗生物質(0.02%ゲンタマイシンおよび0.8%G418)を補足したRPMI 1640培地に維持し、37℃にて5%CO2雰囲気下で、加湿インキュベーター中でインキュベートした。
阻害剤の細胞傷害性を、異なる濃度の式Iの化合物の存在または非存在下で培養したモック感染MT4−CMV−EGFP細胞(150,000細胞/ml)上でアッセイ1の下での実験と並行して測定した。インキュベーションの3日後、細胞増殖の阻害を、EGFP蛍光を測定することによって定量化し、細胞成長を50%阻害する化合物濃度として表した(CC50−表1を参照のこと)。
抗ウイルスアッセイのために、50%ヒト血清の存在下で、MT−4−LTR−EGFP細胞を、RPMI1640培地中の0.001〜0.01CCID50/細胞のMOIにてHIV−1 LAI(IIIB)に感染させた。1時間のインキュベーション後、細胞を洗浄し、10%ウシ胎仔血清(FCS)、または50%ヒト血清の存在下で、連続希釈の化合物を含有する96ウェルプレートに播種した。インキュベーションの4日後、50%ヒト血清の存在下でのEC50(EC50/HS−表1を参照のこと)を、(Fields,R.D.,およびM.V.Lancaster(1993)Am.Biotechnol.Lab.11:48−50によって記載されているように)レザズリンを用いる細胞生存アッセイによって測定した。
HIVインテグラーゼにより媒介される3’−プロセシングの阻害を生化学分析において測定した。このために、短い(約20bp)二本鎖U5 LTR基質を、10mMのTris pH8.0、100mMのNaCl(95℃まで加熱し、30分にわたって室温まで徐々に冷却する)中の5μMの5’−TGTGGAAAATCTCTAGCAGT−3’−alx488(配列番号1)と、7μMのdabcyl−5’−ACTGCTAGAGATTTTCCACA(配列番号2)とのハイブリダイゼーションによって生成した。インテグラーゼ阻害剤を、異なる濃度の試験化合物の存在または非存在下で、反応バッファー(25mMのMOPS pH7.2、10mMのDTT、10mMのMgCl2、15mMのグルタミン酸カリウムおよび2.5%のDMSO)中の150nMの組換えHIV−1インテグラーゼ、100nMの組換えLEDGFおよび50nMのU5 LTR基質のインキュベーションによって測定した。37℃にて2時間後、1/5容量の0.5%SDSを加えることによって反応を停止し、蛍光を測定し(488nmにおける励起、538nmにおける発光)、HIVインテグラーゼの50%阻害に必要な阻害濃度として表した(IC50−表1を参照のこと)。
Claims (15)
- Wが、−NH−または−N(CH3)−である、請求項1に記載の化合物またはその医薬的に許容可能な塩。
- Xが、結合または−S(=O)2−である、請求項1または2に記載の化合物またはその医薬的に許容可能な塩。
- Yが、C4−5アルキレンである、請求項1〜3のいずれか一項に記載の化合物またはその医薬的に許容可能な塩。
- Wがピペラジンである場合、Xは、−C(=O)−であり、Yは、C3−4 アルキレンである、請求項1に記載の化合物またはその医薬的に許容可能な塩。
- Zが、−O−である、請求項1〜5のいずれか一項に記載の化合物またはその医薬的に許容可能な塩。
- Zが、−NH−C(=O)−である、請求項1〜5のいずれか一項に記載の化合物またはその医薬的に許容可能な塩。
- −W−X−Y−Z−リンカーが、8または9個の原子長である、請求項1〜7のいずれか一項に記載の化合物またはその医薬的に許容可能な塩。
- 請求項1〜12のいずれか一項に記載の化合物またはその医薬的に許容可能な塩、および担体を含む、医薬組成物。
- 治療に使用するための、請求項1〜12のいずれか一項に記載の化合物またはその医薬的に許容可能な塩を含む、医薬組成物。
- 請求項1〜12のいずれか一項に記載の化合物またはその医薬的に許容可能な塩を含む、HIV複製の阻害剤。
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PCT/EP2010/065300 WO2011045330A1 (en) | 2009-10-13 | 2010-10-13 | Macrocyclic integrase inhibitors |
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Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2487176A1 (en) * | 2011-02-14 | 2012-08-15 | Elanco Animal Health Ireland Limited | Macrocyclic integrase inhibitors for use in the treatment of feline immunodeficiency virus |
WO2014008636A1 (en) * | 2012-07-11 | 2014-01-16 | Merck Sharp & Dohme Corp. | Macrocyclic compounds as hiv integrase inhibitors |
WO2014099586A1 (en) | 2012-12-17 | 2014-06-26 | Merck Sharp & Dohme Corp. | 4-pyridinonetriazine derivatives as hiv integrase inhibitors |
EP2986291B1 (en) | 2013-04-16 | 2020-05-27 | Merck Sharp & Dohme Corp. | 4-pyridone derivative compounds and uses thereof as hiv integrase inhibitors |
ME02977B (me) | 2013-05-17 | 2018-10-20 | Merck Sharp & Dohme | Fuzionisana triciklicna heterociklicna jedinjenja као inhibiтori hiv integraze |
WO2014200880A1 (en) | 2013-06-13 | 2014-12-18 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
KR102102516B1 (ko) | 2013-09-27 | 2020-04-20 | 머크 샤프 앤드 돔 코포레이션 | Hiv 인테그라제 억제제로서 유용한 치환된 퀴놀리진 유도체 |
WO2016187788A1 (en) | 2015-05-25 | 2016-12-01 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds useful for treating hiv infection |
WO2017004342A1 (en) | 2015-07-02 | 2017-01-05 | Tp Therapeutics, Inc. | Chiral diaryl macrocycles as modulators of protein kinases |
EP3733187A1 (en) | 2015-07-21 | 2020-11-04 | Turning Point Therapeutics, Inc. | Chiral diaryl macrocycle and use thereof in the treatment of cancer |
EP3377066B1 (en) | 2015-11-17 | 2021-04-07 | Merck Sharp & Dohme Corp. | Amido-substituted pyridotriazine derivatives useful as hiv integrase inhibitors |
WO2017106071A1 (en) | 2015-12-15 | 2017-06-22 | Merck Sharp & Dohme Corp. | Spirocyclic quinolizine derivatives useful as hiv integrase inhibitors |
WO2017113288A1 (en) | 2015-12-31 | 2017-07-06 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
JOP20190130A1 (ar) | 2016-12-02 | 2019-06-02 | Merck Sharp & Dohme | مركبات حلقية غير متجانسة رباعية الحلقات مفيدة كمثبطات إنزيم مدمج لفيروس نقص المناعة البشرية (hiv) |
CN110062627A (zh) | 2016-12-02 | 2019-07-26 | 默沙东公司 | 可用作hiv整合酶抑制剂的三环杂环化合物 |
TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
US10786488B2 (en) | 2017-01-26 | 2020-09-29 | Merck Sharp & Dohme Corp. | Substituted quinolizine derivatives useful as HIV integrase inhibitors |
BR112020001695A2 (pt) | 2017-07-28 | 2020-07-21 | Turning Point Therapeutics, Inc. | compostos macrocíclicos e usos dos mesmos |
BR112020012319A2 (pt) | 2017-12-19 | 2020-11-24 | Turning Point Therapeutics, Inc. | compostos macrocíclicos para tratar doença |
HRP20221074T1 (hr) | 2019-03-22 | 2022-11-11 | Gilead Sciences, Inc. | Premošteni triciklički spojevi karbamoilpiridona i njihove farmaceutske uporabe |
AU2021225809B2 (en) | 2020-02-24 | 2023-08-24 | Gilead Sciences, Inc. | Tetracyclic compounds for treating HIV infection |
CN112358477A (zh) * | 2020-11-10 | 2021-02-12 | 牡丹江医学院 | 一种用于治疗胆囊炎的药物及其制备方法 |
PT4196479T (pt) | 2021-01-19 | 2024-01-03 | Gilead Sciences Inc | Compostos de piridotriazinas substituídos e suas utilizações |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CS210880B1 (cs) | 1979-10-19 | 1982-01-29 | Jiri Krepelka | Substituované imidy kyselin 4-arylnaftalen-2,3-dikarboxylových |
CS225002B1 (cs) | 1980-12-12 | 1984-02-13 | Krepelka Jiri | Deriváty 9-fenyl-1H-benzo/f/isoindol-1,3-dionu a způsob jejich výroby |
JPH04217684A (ja) | 1990-05-30 | 1992-08-07 | Shionogi & Co Ltd | アルド−ス還元酵素阻害物質 |
CA2176011A1 (en) * | 1994-09-13 | 1996-03-21 | Yoshiaki Nonomura | Anti-hiv drug |
AU1532802A (en) | 2000-10-12 | 2002-04-22 | Merck & Co Inc | Aza- and polyaza-naphthalenyl-carboxamides useful as hiv integrase inhibitors |
ATE345129T1 (de) | 2000-10-12 | 2006-12-15 | Merck & Co Inc | Aza- und polyaza-naphthalenylcarbonsäureamide als hiv-integrase-hemmer |
US20050010048A1 (en) | 2000-10-12 | 2005-01-13 | Linghang Zhuang | Aza-and polyaza-naphthalenly ketones useful as hiv integrase inhibitors |
SK4322003A3 (en) | 2000-10-12 | 2003-09-11 | Merck & Co Inc | Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors |
AU2003301439A1 (en) | 2002-10-16 | 2004-05-04 | Gilead Sciences, Inc. | Pre-organized tricyclic integrase inhibitor compounds |
BRPI0306214B1 (pt) | 2002-11-20 | 2017-08-08 | Japan Tobacco Inc. | 4-oxoquinoline compound and use of this as a hiv integrase inhibitor |
US7414045B2 (en) | 2002-12-27 | 2008-08-19 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Substituted pyrimido[1,2-a]azepines useful as HIV integrase inhibitors |
US6890942B2 (en) | 2003-05-16 | 2005-05-10 | Bristol-Myers Squibb Company | Acyl sulfonamides as inhibitors of HIV integrase |
AU2004274493A1 (en) | 2003-09-19 | 2005-03-31 | Gilead Sciences, Inc. | Aza-quinolinol phosphonate integrase inhibitor compounds |
CN1930161A (zh) | 2004-03-09 | 2007-03-14 | P·安杰莱蒂分子生物学研究所 | Hiv整合酶抑制剂 |
US7176196B2 (en) | 2004-05-28 | 2007-02-13 | Bristol-Myers Squibb Company | Bicyclic heterocycles as HIV integrase inhibitors |
HUE044978T2 (hu) | 2005-04-28 | 2019-11-28 | Viiv Healthcare Co | HIV integráz gátló aktivitású policiklusos karbamoilpiridon származék |
JP2009503081A (ja) * | 2005-08-04 | 2009-01-29 | スミスクライン ビーチャム コーポレーション | Hivインテグラーゼ阻害薬 |
EA200801144A1 (ru) * | 2005-10-27 | 2008-10-30 | Сионоги Энд Ко., Лтд. | Полициклическое карбамоилпиридоновое производное, обладающее ингибиторной активностью в отношении интегразы вич |
US8039458B2 (en) * | 2005-11-17 | 2011-10-18 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
TW200811153A (en) | 2006-06-23 | 2008-03-01 | Japan Tobacco Inc | 6-(heterocyclyl-substituted benzyl)-4-oxoquinoline compound and use thereof as HIV integrase inhibitor |
WO2009112439A1 (en) * | 2008-03-10 | 2009-09-17 | Janssen Pharmaceutica Nv | 4-aryl-2-anilino-pyrimidines as plk kinase inhibitors |
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CA2777664A1 (en) | 2011-04-21 |
NZ598766A (en) | 2013-09-27 |
AU2010305805B2 (en) | 2014-04-03 |
US8497270B2 (en) | 2013-07-30 |
KR20120087916A (ko) | 2012-08-07 |
EA201270540A1 (ru) | 2012-09-28 |
CN102574854A (zh) | 2012-07-11 |
CN102574854B (zh) | 2014-04-16 |
CA2777664C (en) | 2014-06-10 |
BR112012008586A2 (pt) | 2016-11-29 |
JP2013507423A (ja) | 2013-03-04 |
AU2010305805A1 (en) | 2012-04-19 |
EA019558B1 (ru) | 2014-04-30 |
ZA201202516B (en) | 2013-09-25 |
EP2488521A1 (en) | 2012-08-22 |
IL218845A0 (en) | 2012-06-28 |
EP2488521B1 (en) | 2013-12-18 |
MX2012004426A (es) | 2012-07-30 |
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