CN102206177A - 1-naphthyl benzophenone derivatives, and preparation method and application thereof - Google Patents

1-naphthyl benzophenone derivatives, and preparation method and application thereof Download PDF

Info

Publication number
CN102206177A
CN102206177A CN2011100995745A CN201110099574A CN102206177A CN 102206177 A CN102206177 A CN 102206177A CN 2011100995745 A CN2011100995745 A CN 2011100995745A CN 201110099574 A CN201110099574 A CN 201110099574A CN 102206177 A CN102206177 A CN 102206177A
Authority
CN
China
Prior art keywords
alkyl
compound
optional
naphthyl
cyano group
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
CN2011100995745A
Other languages
Chinese (zh)
Inventor
陈芬儿
马晓东
古双喜
何秋琴
郑永唐
张旋
杨柳萌
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fudan University
Kunming Institute of Zoology of CAS
Original Assignee
Fudan University
Kunming Institute of Zoology of CAS
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 Fudan University, Kunming Institute of Zoology of CAS filed Critical Fudan University
Priority to CN2011100995745A priority Critical patent/CN102206177A/en
Publication of CN102206177A publication Critical patent/CN102206177A/en
Pending legal-status Critical Current

Links

Abstract

The invention belongs to the technical field of medicaments, and specifically relates to 1-naphthyl benzophenone derivatives with a structural formula shown in formula (I), pharmaceutical salts thereof, stereochemical isomers thereof, hydrates and solvates thereof, polycrystals or eutectic crystals thereof, precursors and derivatives with identical biological functions thereof, a preparation method thereof, a composition containing one or more the 1-naphthyl benzophenone derivatives and application thereof in the relating drugs for treating AIDS (acquired immune deficiency syndrome) and the like. Pharmacological experiment results show that most of the 1-naphthyl benzophenone derivatives have strong inhibition activity (nanomolar level) to the duplication of wile-type HIV (human immunodeficiency virus)-1strain (IIIB), and partial 1-naphthyl benzophenone derivatives have strong inhibition activity to multiple drug-resistant HIV-1 strain (K103N + Y181C), so that the 1-naphthyl benzophenone derivatives can be used as anti-HIV drug candidates.

Description

1-naphthyl methanone derivatives and its production and use
Technical field
The invention belongs to medical technical field, be specifically related to 1-naphthyl methanone derivatives, its hydrate and solvate, its polycrystalline and eutectic, the precursor of its same biological function and derivative, also relate to its preparation method, and contain one or more these type of compound compositions, and the application in related drugs such as treatment acquired immune deficiency syndrome (AIDS).This series compound not only duplicates wild-type HIV-1 strain (IIIB) has very strong inhibition activity (nmole level), and the multiple resistance HIV-1 virus strain of part of compounds (K103N+ Y181C) also has stronger inhibition activity.
Background technology
The acquired immune deficiency syndrome (AIDS) (AIDS) that human immunodeficiency virus (HIV) causes is one of scientific circles' chronic disease of being difficult to capture, be eruption and prevalence trend, bring serious threat for human existence and development, existing medicine has certain curative effect, also exists problems such as anti-drug resistance is poor, toxic side effect is big simultaneously.Therefore, the anti-AIDS medicine of searching high-efficiency low-toxicity remains the key subjects of pharmaceutical chemistry research.The research and development of present anti-AIDS medicine are mainly based on the understanding of HIV life working cycle, wherein, reversed transcriptive enzyme (RT) has played vital role in the reverse transcription process of geneome RNA, and be the commitment of HIV life replicative cycle, so RT becomes one of important target spot of anti-AIDS drug research.Have in 20 kinds of medicines of FDA approval at present 10 kinds with HIV RT as target spot.
In the existing inverase, non-nucleoside reverse transcriptase inhibitor (NNRTIs) becomes one of focus of various countries' Pharmaceutical Chemist concern because of advantages such as its high-efficiency low-toxicities.At present, the anti-hiv reverse transcriptase inhibitor through U.S. FDA approval listing has four kinds: how Wella is put down (Nevirapine), De Laweiding (Delavirdine), Yi Feiweilun (Efavirenz) and is complied with bent Wei Lin (etravirine).Classical NNRTIs only acts on HIV-1 virus, and invalid to HIV-2 virus.
HIV virus makes medicine ineffective because the characteristic that self easily makes a variation is easy to produce resistance." though drug cocktail therapy (treatment) " (cocktail) and " efficient anti-retroviral therapy " (HAART) simultaneously or a kind of PI of sequential combined utilization and a kind of NNRTI or 2 kinds of NNRTI medicines clinically promptly, have addition or synergy to continuing to suppress virus replication, and can delay or stop the resistance that produces because of the HIV variation, having slowed down to a certain extent is developed to the speed of acquired immune deficiency syndrome (AIDS), and reduces mortality ratio.But, because " chicken tail method therapy " and HAART therapy " exist cross resistance; and toxic side effect is big; cost an arm and a leg; and therapy complexity; as: face and use which kind of drug combination, its drug combination of timing changing and change over problems such as which kind of drug combination, therefore seek the chemical sproof medicine of the viral generation of more efficient inhibition HIV is the research focus in this field always.
Summary of the invention
The objective of the invention is to propose a kind of reverse transcriptase inhibitors 1-naphthyl methanone derivatives.
Another purpose of the present invention is to propose the preparation method of above-claimed cpd.
Still a further object of the present invention is the application that proposes above-claimed cpd.
1992, Glaxo company finds that by high flux screening the derivative with diaryl ketone structure has certain anti-HIV-1 activity, because of its novel structure, the said firm has carried out structural modification research widely subsequently, a series of highly active anti-AIDS drug candidates that have have been developed, this compounds receives much concern owing to the excellent performance aspect anti-drug resistance.The present invention is lead compound with GW678248, B in molecule ring is become naphthalene nucleus, designed the similar thing of benzophenone that a series of naphthalene nucleus replace, being desirably in B ring introduces naphthalene nucleus and can add potent inhibitor and amino-acid residue Tyr188 on every side, Tyr181, Trp229, the π between the Tyr318 ~ pi accumulation effect, thereby improve the inhibition activity of target compound to wild-type HIV-1 and variant viral strain thereof, in the hope of find high reactivity more, more hypotoxicity and more extensive anti-drug resistance HIV-1 RT inhibitor.
The present invention has synthesized the 1-naphthyl methanone derivatives that a series of B-rings replace for naphthalene nucleus, and it has been carried out biological activity test, the result shows that this series compound not only duplicates wild-type HIV-1 strain (IIIB) and has very strong inhibition activity (nmole level), and the multiple resistance HIV-1 virus strain of part of compounds (K103N+ Y181C) also has stronger inhibition activity.
Above-claimed cpd provided by the invention has following general structure:
Ⅰ
Wherein, R 1Be optional phenyl ring, naphthalene nucleus, saturated fatty ring and the C of being substituted 1-4Alkyl, optional substituted C 2-6Thiazolinyl, optional substituted C 2-6Alkynyl.
R 2And R 3Be independently selected from hydrogen respectively, hydroxyl, halogen, optional by cyano group or-C (=O) R 6The C that replaces 1-6Alkyl, C 3-7Cycloalkyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Thiazolinyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Alkynyl, C 1-6Alkoxyl group, C 1-6Carbalkoxy, carboxyl, cyano group, nitro, amino ,-NR 5-, many halogenated methyls, many halogenated methoxies, many halos methylthio group.
R 4Be independently selected from hydrogen respectively, hydroxyl, halogen, optional by cyano group or-C (=O) R 6The C that replaces 1-6Alkyl, C 3-7Cycloalkyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Thiazolinyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Alkynyl, C 1-6Alkoxyl group, C 1-6Carbalkoxy, carboxyl, cyano group, nitro, amino ,-NR 5-, many halogenated methyls, many halogenated methoxies, many halos methylthio group ,-S (=O) pR 6,-NH-S (=O) pR 6,-C (=O) R 6,-NHC (=O) H ,-C (=O) NHNH 2,-NHC (=O) R 6,-C (=NH) R 6
X and Y are independently selected from respectively-NR 5-,-NH-NH-,-N=N-,-O-,-C (=O)-, C 1-4Alkane two bases ,-CH (OH)-,-S-,-S (=O) p-,-X 1-C 1-4Alkane two bases-or-C 1-4Alkane two bases-X 1-,-CH (CN)-.
X 1For-NR 5-,-NH-NH-,-N=N-,-O-,-C (=O)-,-CH (OH)-,-S (=O) p-.
R 5Be independently selected from hydrogen respectively, aryl, formyl radical, C 1-6Alkyl-carbonyl, C 1-6Alkyl, C 1-6Carbalkoxy is by formyl radical, C 1-6Alkyl-carbonyl, C 1-6Carbalkoxy or C 1-6The C that alkyl carbonyl oxy replaces 1-6Alkyl is by C 1-6The C that carbalkoxy replaces 1-6Alkoxyl group or C 1-6Carbalkoxy.
R 6Be C 1-4Alkyl, amino, single or two (C 1-4Alkyl) amino or many halos C 1-4Alkyl.
P is 1-2.
The present invention also provides the preparation method of above-claimed cpd, and the reaction formula of its preparation is as follows:
Figure 2011100995745100002DEST_PATH_IMAGE003
In the formula, the preparation of the compound of structural formula shown in (2) (be called for short compound (2), all the other are similar) with reference to Kwanghee Koh Park etc. ( Tetrahedron,2005, 61, 545-553) and Wan-mei Li etc. ( Synthetic Communications, 2007, 37, 1595 – 1601) report synthetic method; The preparation method of the compound (be called for short compound (3)) of structural formula shown in (3) is with reference to patent WO02/070470, WO2006012733, WO01/17982, US2004/0122064, US2006/0009651; Under alkaline condition, substitution reaction takes place with compound (3) and promptly makes target product in compound (2).
Alkali used in the present invention is a kind of of following mineral alkali: salt of wormwood, yellow soda ash, cesium carbonate, sodium hydride, sodium hydroxide, potassium hydroxide; Perhaps be a kind of of following organic bases: triethylamine, Tributylamine etc., preferred salt of wormwood; Used solvent be acetonitrile, N N-dimethyl formamide, N, N-N,N-DIMETHYLACETAMIDE, tetrahydrofuran (THF), acetone, ethyl acetate, toluene, methylene dichloride or ether, preferred acetone; Temperature of reaction is 0 ℃ ~ 200 ℃, preferred 50 ℃ ~ 70 ℃; Reaction times is 10 min ~ 3 d, preferred 2 ~ 10 h.
Compound of the present invention is a kind of synthetic simple brand-new anti-HIV virus reagent, can be used as the drug candidates of anti-HIV.The biological activity test of cell levels shows:
This compounds generally has good anti-HIV-1 virus activity, and wherein part of compounds not only demonstrates other biological activity of nmole level, and demonstrates higher selectivity index, can further be developed as anti-AIDS medicine.
Therefore, the present invention also provides a kind of pharmaceutical composition, and this pharmaceutical composition contains foregoing arbitrary compound of effective dose and pharmaceutical carrier.
The present invention also comprise arbitrary compound as previously mentioned from pharmaceutically acceptable prodrug and derivative.
The present invention also comprises the arbitrary application in preparation prevention and treatment AIDS-treating medicine of arbitrary as previously mentioned compound.
The present invention also comprises the application of arbitrary as previously mentioned compound in preparation prevention and medicine for treating tumor thing, and described tumour is a carcinoma of the pancreas, colorectal cancer, bladder cancer, mammary cancer, ovarian cancer, squamous cell carcinoma, incidence cancer, non-small cell carcinoma.
Embodiment:
The present invention will be helped to understand by following embodiment, but content of the present invention can not be limited.
The preparation of embodiment 1:1-naphthyl methanone derivatives
The preparation of compound (2) with reference to Kwanghee Koh Park etc. ( Tetrahedron,2005, 61, 545-553) and Wan-mei Li etc. ( Synthetic Communications, 2007, 37, 1595 – 1601) report synthetic method; The preparation method of compound (3) is with reference to patent WO02/070470, WO2006012733, WO01/17982, US2004/0122064, US2006/0009651; Compound (2) and compound (3) in 50 ℃ of reaction 2 h, promptly get target product under the salt of wormwood effect.Below with R 1=3,5-dimePhenyl, R 2=Br, R 3=Me, R 4=NH 2SO 2, X=O, Y=NH are specific examples, set forth the preparation method of target compound, but protection scope of the present invention are not limited to this.
Figure 2011100995745100002DEST_PATH_IMAGE005
Compound (4) (0.355 g, 1.000 mol) and compound (5) (0.355 g, 1.000 mol) are dissolved in the 20 mL acetone, add sodium borohydride (0.369 g, 1.200 mol) again, back flow reaction 2 h, ethyl acetate extraction (3 * 50 mL) is poured reaction solution in the water in cooling, merge organic layer, the saturated common salt washing is (50 mL) once, anhydrous sodium sulfate drying, and column chromatography for separation gets target compound (6), white solid 0.398 g, yield 63.7%.
Yield?63.7%;?off-white?solid,?mp?210.4-211.9℃;? 1H?NMR?(DMSO- d 6)? δ?(ppm):?2.10?(s,?3H,?C H 3 ),?2.12?(s,?3H,?C H 3 ),?2.17?(s,?3H,?C H 3 ),?4.89?(s,?2H,?C H 2 ),?7.25?(s,?2H,?N H 2 ),?7.28-8.27?(m,?11H,?Ph H,Naph H),?9.27?(s,?H,?N H);? 13C?NMR?(DMSO- d 6 )? δ:?16.3,?17.6,?20.0,?68.0,?116.3,?117.4,?123.8?(2C),?124.8,?125.4,?125.7,?127.7,?128.7,?129.5,?130.0,?130.2,?130.7,?130.8,?131.2,?133.8,?136.8,?138.2,?138.4,?138.5,?140.4,?153.0,?166.3,?196.7;?MS?(ESI)? m/z?,?580?(M +?-?H),;?Anal.?(C 28H 25BrN 2O 5S)?C,?H,?N,?Br,?S,?O.
N-[4-(Aminosulfonyl)-2-methylphenyl]-2-(1-benzoyl-2-naphenoxy)acetamide?(10a).
Yield?66.9%;?off-white?solid,?mp?181.2-182.1℃;? 1H?NMR?(DMSO- d 6)? δ?(ppm):?2.16?(s,?3H,?C H 3 ),?4.92?(s,?2H,?C H 2 ),?7.28?(s,?2H,?N H 2 ),?7.38-8.16?(m,?14H,?Ph H,Naph H),?9.26?(s,?H,?N H);? 13C?NMR?(DMSO- d 6 )? δ:?17.5,?67.8,?114.6,?122.3,?122.4,?123.4,?123.5,?123.8,?124.4,?127.6,?128.3,?128.7,?129.0?(2C),?129.2?(2C),?130.8,?130.9,?131.3,?134.0,?137.1,?138.4,?140.2,?152.3,?168.4,?196.9;?MS?(ESI -)? m/z?473?(M +-H);?Anal.?(C 26H 22N 2O 5S)?C,?H,?N,?S,?O.
N-[4-(Aminosulfonyl)-2-methylphenyl]-2-(6-bromo-1-benzoyl-2-naphenoxy)acetamide?(10j).
Yield?60.3%;?off-white?solid,?mp?213.3-214.5℃;? 1H?NMR?(DMSO- d 6)? δ?(ppm):?2.17?(s,?3H,?C H 3 ),?4.94?(s,?2H,?C H 2 ),?7.28?(s,?2H,?N H 2 ),?7.31-7.83?(m,?13H,?Ph H,Naph H),?9.30?(s,?H,?N H);? 13C?NMR?(DMSO- d 6 )? δ:?17.6,?67.9,?115.8,?117.3,?122.3,?123.6,?123.8,?125.6,?127.5,?129.0,?129.3?(2C),?129.4?(2C),?129.8,?130.2,?130.6?(2C),?131.0,?134.2,?137.0,?138.5,?140.2,?152.8,?166.3,?196.1;?MS?(ESI -)? m/z?552?(M +-H);?Anal.?(C 26H 21BrN 2O 5S)?C,?H,?Br,?N,?S,?O.
N-[4-(Aminosulfonyl)-2-methylphenyl]-2-[6-cyano-1-(3-methylbenzoyl)-2-naphenoxy]acetamide?(10s).
Yield?56.9%;?off-white?solid,?mp?228.9-230.8℃;? 1H?NMR?(DMSO- d 6)? δ?(ppm):?2.17?(s,?3H,?C H 3 ),?2.28?(s,?3H,?C H 3 ),?5.00?(s,?2H,?C H 2 ),?7.26?(s,?2H,?N H 2 ),?7.35-8.28?(m,?12H,?Ph H,Naph H),?9.34?(s,?H,?N H);? 13C?NMR?(DMSO- d 6 )? δ:?17.7,?20.8,?67.5,?106.7,?116.3,?119.1,?122.6,?123.8,?123.9,?124.9,?125.8,?126.9,?127.6,?127.8,?128.1,?129.1,?129.5,?129.6,?130.6,?132.3,?132.6,?135.0,?135.1,?137.0,?138.6,?138.7,?156.0,?166.3,?196.0;?MS?(ESI -)? m/z?513?(M +-H);?Anal.?(C 29H 23N 3O 5S)?C,?H,?N,?S,?O.。
Embodiment 2 anti-HIV biological activity tests
Compound is to the toxicity test of C8166 cell
Testing compound is carried out 5 times of doubling dilutions with RPMI-1640 perfect medium (containing 10% FBS) on 96 hole microtest plates, each extent of dilution is established 3 holes, every hole 100 μ L.The control wells that does not contain medicine is set simultaneously.Every hole adds 4 * 10 5The C8166 cell 100 μ L of/mL.In 37 ℃, 5% CO 2Cultivated 3 days, and adopted the MTT colorimetry to detect cytotoxicity.The ELx800 microplate reader is measured the OD value, and measuring wavelength is 570 nm, and reference wavelength is 630 nm.Calculate CC 50Value (50% Cytotoxic concentration), the compound concentration during promptly to 50% normal T lymphocyte series C8166 toxigenicity.
Compound is to the inhibition experiment of HIV cytopathogenic effect (CPE)
Testing compound is carried out 5 times of doubling dilutions with RPMI-1640 perfect medium (containing 10% FBS) on 96 hole microtest plates, each extent of dilution is established 3 repeating holes, every hole 100 μ L.The control wells that does not contain medicine is set simultaneously.Every hole adds 8 * 10 5The C8166 cell 50 μ l of/mL add the HIV-1 of 50 μ L then IIIB, HIV-1 A17Or HIV-2 RODThe dilution supernatant, 1300 TCID 50/ hole.The positive medicine contrast of AZT.In 37 ℃, 5% CO 2Cultivated 3 days, (100 *) count plasmodial formation under the inverted microscope.EC 50(50% Effective concentration) forms 50% o'clock compound concentration for suppressing synplasm.
The present invention compares product with GW678248 and AZT, and the part target compound the results are shown in Table 1 to the inhibition activity of HIV.
Figure 987911DEST_PATH_IMAGE006
Compd ?EC 50(nM) a ?CC 50 (nM) b SI c
10a 52.7 33813.5 641.8
10g 608.9 33025.6 54.2
10h 27.1 36598.2 1348.9
10j 4607.7 29191.2 6.3
10s 790.6 15155.0 19.2
GW678248 0.7 >385.8 567382
AZT 10.6 5601.7 528975.3
aEC 50: ?effective?concentration?of?compound?required?to?protect?the?cell?against?viral?bytopathogenicity?by
Experimental result shows that the compound that is comprised in the chemical structure of general formula generally has stronger anti-HIV-1 virus activity, less cytotoxicity and higher selectivity index.
The invention is not restricted to above-mentioned example.

Claims (7)

1. 1-naphthyl methanone derivatives is characterized in that having following structural formula:
Figure 2011100995745100001DEST_PATH_IMAGE002
（ 1）
Wherein, R 1Be optional phenyl ring, naphthalene nucleus, saturated fatty ring and the C of being substituted 1-4Alkyl, optional substituted C 2-6Thiazolinyl, optional substituted C 2-6Alkynyl;
R 2And R 3Be independently selected from hydrogen respectively, hydroxyl, halogen, optional by cyano group or-C (=O) R 6The C that replaces 1-6Alkyl, C 3-7Cycloalkyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Thiazolinyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Alkynyl, C 1-6Alkoxyl group, C 1-6Carbalkoxy, carboxyl, cyano group, nitro, amino ,-NR 5-, many halogenated methyls, many halogenated methoxies, many halos methylthio group;
R 4Be independently selected from hydrogen respectively, hydroxyl, halogen, optional by cyano group or-C (=O) R 6The C that replaces 1-6Alkyl, C 3-7Cycloalkyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Thiazolinyl, optional by the C of one or more halogen atoms or cyano group replacement 2-6Alkynyl, C 1-6Alkoxyl group, C 1-6Carbalkoxy, carboxyl, cyano group, nitro, amino ,-NR 5-, many halogenated methyls, many halogenated methoxies, many halos methylthio group ,-S (=O) pR 6,-NH-S (=O) pR 6,-C (=O) R 6,-NHC (=O) H ,-C (=O) NHNH 2,-NHC (=O) R 6,-C (=NH) R 6
X and Y are independently selected from respectively-NR 5-,-NH-NH-,-N=N-,-O-,-C (=O)-, C 1-4Alkane two bases ,-CH (OH)-,-S-,-S (=O) p-,-X 1-C 1-4Alkane two bases-or-C 1-4Alkane two bases-X 1-,-CH (CN)-;
X 1For-NR 5-,-NH-NH-,-N=N-,-O-,-C (=O)-,-CH (OH)-,-S (=O) p-;
R 5Be independently selected from hydrogen respectively, aryl, formyl radical, C 1-6Alkyl-carbonyl, C 1-6Alkyl, C 1-6Carbalkoxy is by formyl radical, C 1-6Alkyl-carbonyl, C 1-6Carbalkoxy or C 1-6The C that alkyl carbonyl oxy replaces 1-6Alkyl is by C 1-6The C that carbalkoxy replaces 1-6Alkoxyl group or C 1-6Carbalkoxy;
R 6Be C 1-4Alkyl, amino, single or two (C 1-4Alkyl) amino or many halos C 1-4Alkyl;
P is 1-2.
2. the preparation method of a 1-naphthyl methanone derivatives as claimed in claim 1 is characterized in that the chemical equation for preparing is:
Figure 2011100995745100001DEST_PATH_IMAGE004
In the formula, structural formula is that second compound shown in (2) and structural formula are the 3rd compound generation substitution reaction shown in (3), promptly makes target product.
3. preparation method as claimed in claim 2, it is characterized in that second compound ( 2) and the 3rd compound ( 3) the employed alkali of substitution reaction takes place is: following mineral alkali a kind of: salt of wormwood, yellow soda ash, cesium carbonate, sodium hydride, sodium hydroxide, potassium hydroxide perhaps are a kind of of following organic bases: triethylamine, Tributylamine etc.; Used solvent be acetonitrile, N, N-dimethyl formamide, N, N-N,N-DIMETHYLACETAMIDE, tetrahydrofuran (THF), acetone, ethyl acetate, toluene, methylene dichloride or ether; Temperature of reaction is 0 ℃～200 ℃; Reaction times is 10 min～3 d.
4. a pharmaceutical composition is characterized in that containing effective dose arbitrary compound as claimed in claim 1 and pharmaceutical carrier.
One kind according to claim 1 compound from pharmaceutically acceptable prodrug and derivative.
6. one kind as claim 1, one of 4,5 application of described compound in preparation prevention and treatment AIDS-treating medicine.
7. one kind as claim 1, one of 4,5 application of described compound in preparation prevention and medicine for treating tumor thing, and described tumour is a carcinoma of the pancreas, colorectal cancer, bladder cancer, mammary cancer, ovarian cancer, squamous cell carcinoma, incidence cancer, non-small cell carcinoma.
CN2011100995745A 2011-04-20 2011-04-20 1-naphthyl benzophenone derivatives, and preparation method and application thereof Pending CN102206177A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN2011100995745A CN102206177A (en) 2011-04-20 2011-04-20 1-naphthyl benzophenone derivatives, and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN2011100995745A CN102206177A (en) 2011-04-20 2011-04-20 1-naphthyl benzophenone derivatives, and preparation method and application thereof

Publications (1)

Publication Number Publication Date
CN102206177A true CN102206177A (en) 2011-10-05

Family

ID=44695272

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2011100995745A Pending CN102206177A (en) 2011-04-20 2011-04-20 1-naphthyl benzophenone derivatives, and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN102206177A (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001017982A1 (en) * 1999-09-04 2001-03-15 Glaxo Group Limited Benzophenones as inhibitors of reverse transcriptase
US20040122064A1 (en) * 2001-03-02 2004-06-24 Chan Joseph Howing Benzophenones as inhibitors of reverse transcriptase
US20080114068A1 (en) * 2004-08-02 2008-05-15 Boehringer Ingelheim International Gmbh Benzoic acid derivatives as non nucleoside reverse-transcriptase inhibitors
CN101287702A (en) * 2005-10-19 2008-10-15 弗·哈夫曼-拉罗切有限公司 N-phenyl phenylacetamide non-nucleoside reverse transcriptase inhibitors
CN101484418A (en) * 2006-07-21 2009-07-15 弗·哈夫曼-拉罗切有限公司 Non-nucleoside reverse transcriptase inhibitors

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001017982A1 (en) * 1999-09-04 2001-03-15 Glaxo Group Limited Benzophenones as inhibitors of reverse transcriptase
US20040122064A1 (en) * 2001-03-02 2004-06-24 Chan Joseph Howing Benzophenones as inhibitors of reverse transcriptase
US20080114068A1 (en) * 2004-08-02 2008-05-15 Boehringer Ingelheim International Gmbh Benzoic acid derivatives as non nucleoside reverse-transcriptase inhibitors
CN101287702A (en) * 2005-10-19 2008-10-15 弗·哈夫曼-拉罗切有限公司 N-phenyl phenylacetamide non-nucleoside reverse transcriptase inhibitors
CN101484418A (en) * 2006-07-21 2009-07-15 弗·哈夫曼-拉罗切有限公司 Non-nucleoside reverse transcriptase inhibitors

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JOSEPH H. CHAN等: "Novel Benzophenones as Non-nucleoside Reverse Transcriptase Inhibitors of HIV-1", 《JOURNAL OF MEDICINAL CHEMISTRY》 *
SRIVASTAVA, VANDANA等: "Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 *

Similar Documents

Publication Publication Date Title
EP2864338B1 (en) 7-oxo-thiazolopyridine carbonic acid derivatives and their use in the treatment, amelioration or prevention of a viral disease
AU2018203354A1 (en) Hepatitis B antiviral agents
WO2013174931A1 (en) 7-oxo-4,7 -dihydro- pyrazolo [1, 5 -a] pyrimidine derivatives which are useful in the treatment, amelioration or prevention of a viral disease
WO2019141179A1 (en) Pyridone derivative, composition thereof and application thereof as anti-influenza drug
JP2015524457A (en) Dihydroxypyrimidine carbonic acid derivatives and their use in the treatment, amelioration or prevention of viral diseases
KR20150033645A (en) 1,3-dihydro-2h-benzimidazol-2-one derivatives substituted with benzimidazoles as respiratory syncytial virus antiviral agents
WO2016040084A1 (en) Inhibitors of human immunodeficiency virus replication
WO2014128213A1 (en) Compounds for use in inhibiting hiv capsid assembly
WO2006044975A2 (en) Compositions and their use as anti-tumor agents
TW201726678A (en) Pyrimidone derivatives and their use in the treatment, amelioration or prevention of a viral disease
CA2949785A1 (en) Mth1 inhibitors for treatment of cancer
Fan et al. Discovery of 5, 6-dihydro-indolo [1, 2-a] quinoxaline derivatives as new HIV-1 inhibitors in vitro
WO2017160753A1 (en) Novel selenazolidine and thiazolidine compounds for treating cancer and other diseases
WO2017046318A1 (en) Triazolones derivatives for use in the treatment, amelioration or prevention of a viral disease
WO2017158147A1 (en) Pyrimidone derivatives and their use in the treatment, amelioration or prevention of a viral disease
CN102206177A (en) 1-naphthyl benzophenone derivatives, and preparation method and application thereof
CN103732575A (en) Diarylaniline or diarylpyridinamine compound and preparation method and medical use thereof
CN102219717A (en) N-phenyl aryl formamide derivative, preparation method thereof and use thereof
Che et al. Synthesis and in vitro anti-HIV-1 evaluation of some N-arylsulfonyl-3-formylindoles
CN102153517B (en) Diaryl pyrimidone hydrazone derivatives and preparation method and application of diaryl pyrimidone hydrazone derivatives
CN109666022A (en) Triazole derivatives and its preparation method and application
RU2017139799A (en) PREPARATION AND USE OF KINASE INHIBITOR
WO2017196261A1 (en) Jak and hdac dual-inhibitor compounds
CN102229547A (en) Naphthyl phenyl ether benzenesulfonamide derivative and preparation method and purpose thereof
KR20220110795A (en) 2-(4-Chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoro Method for preparing acetamide

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20111005

RJ01 Rejection of invention patent application after publication