CN102212022A - Diphenyl methanol derivatives and preparation method and application thereof - Google Patents
Diphenyl methanol derivatives and preparation method and application thereof Download PDFInfo
- Publication number
- CN102212022A CN102212022A CN2011100995779A CN201110099577A CN102212022A CN 102212022 A CN102212022 A CN 102212022A CN 2011100995779 A CN2011100995779 A CN 2011100995779A CN 201110099577 A CN201110099577 A CN 201110099577A CN 102212022 A CN102212022 A CN 102212022A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- optional
- cyano group
- compound
- carbalkoxy
- 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
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicaments, and in particular relates to diphenyl methanol derivatives and a preparation method and application thereof. The structural formula of the compounds is shown as a formula (I). The invention also relates to medicinal salts, stereoscopic chemistry isomers, hydrates, solvates, polycrystal or eutectic products, precursors and derivatives of the same biological function of the compounds, a preparation method of the compounds, a composition containing one or more compounds, and application of the compounds in related medicaments for treating Aids and the like. The pharmacological experiment results show that most of the compounds have certain inhibiting activity on wild HIV-1 strain (IIIB) replication, and can be used for further structure modification of anti-HIV precursors and used for developing novel anti-HIV medicaments.
Description
Technical field
The invention belongs to medical technical field, be specifically related to the described benzhydrol derivative of general formula (1), its hydrate and solvate, its polycrystalline and eutectic, the precursor of its same biological function and derivative, 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).Major part is duplicated certain inhibition activity to wild-type HIV-1 strain (IIIB) in this series compound, can be used as the further structural modification of anti-HIV guide's thing.
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, the speed and the reduction mortality ratio that have slowed down to a certain extent and be developed to acquired immune deficiency syndrome (AIDS).But, because " chicken tail method therapy " and HAART therapy " exist cross resistance; toxic side effect is big; cost an arm and a leg; and therapy is complicated as: at first 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 inhibitions 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 benzhydrol derivative.
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.Wyatt, P. G etc. (
J. Med. Chem.1995,
381657-1665) report is with this type of compd A, carbonyl reduction between the B ring becomes the resulting benzhydrol derivative of hydroxyl anti-HIV-1 activity to completely lose, structure activity study has subsequently all kept this carbonyl, find simultaneously to introduce the bigger sulfuryl amine group of wetting ability in the C-4 position of C ring, can greatly improve the HIV (human immunodeficiency virus)-resistant activity and the anti-drug resistance of compound, when existing in order further to investigate this sulfuryl amine group, with the ketone carbonyl reduction is the influence of alcoholic extract hydroxyl group to molecular activity, the present invention adopts the means of area of computer aided SARS drug design to simulate the mode of action of such inhibitor and HIV-1 RT, with the diaryl ketone construction recovery is diarylcarbinols, change the flexibility of molecule on the one hand, add potent inhibitor and amino-acid residue Tyr188 on every side with this, Tyr181, Trp229, the π between the Tyr318～pi accumulation effect; Simultaneously hydroxyl can with amino-acid residue generation hydrogen bond action, disturb the katalysis of amino-acid residue Asp, a series of diarylcarbinols derivatives have been synthesized in design, and it has been carried out biological activity test, the result shows that major part is duplicated certain inhibition activity to wild-type HIV-1 strain (IIIB) in this series compound, can be used as the further structural modification of anti-HIV guide's thing, designed and synthesized the benzhydrol derivative of a series of brand news.
Above-claimed cpd provided by the invention (benzhydrol derivative) 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 reaction formula of the preparation of above-claimed cpd is as follows:
In the above-mentioned reaction formula, the preparation method of the different substitution compounds of structural formula is with reference to patent WO02/070470, WO2006012733, WO01/17982, US2004/0122064, US2006/0009651 shown in (2); Different going back under original reagent, different solvents and the differing temps, the ketone carbonyl of the compound of structural formula (2) is reduced to hydroxyl and makes target compound shown in (2).
Among the present invention, reductive condition is metal catalytic hydrogenations such as Pt, Ni, borane reagent reduction, pure aurin tricarboxylic acid reduction and sodium borohydride or potassium borohydride reduction; Solvent is THF, acetonitrile, methylene dichloride, ethylene dichloride, ether, isopropyl ether, methyl tertiary butyl ether, toluene, dimethylbenzene, ethyl acetate, methyl alcohol, ethanol, Virahol etc., and temperature of reaction is 0～200 ℃, and preferable reaction temperature is preferred 50 ℃ ~ 70 ℃.
Compound of the present invention is a kind of synthetic simple brand-new anti HIV-1 virus reagent, can further be developed as the material standed for of inverase.The biological activity test of cell levels shows that 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.
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 invention still further relates to compound as previously mentioned from pharmaceutically acceptable prodrug and derivative.
The present invention also proposes the application of compound in preparation prevention and treatment AIDS-treating medicine as previously mentioned.
The present invention also proposes the application of compound in preparation prevention and medicine for treating tumor thing as previously mentioned.Described tumour comprises 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.
Embodiment 1: the preparation of benzhydrol derivative
The preparation of compound (2) is with reference to patent WO02/070470, WO2006012733, WO01/17982, US2004/0122064, US2006/0009651.Compound (2) makes compound (1) through reduction, reductive condition is: metal catalytic hydrogenations such as Pt, Ni, borane reagent reduction, pure aurin tricarboxylic acid reduction and sodium borohydride or potassium borohydride reduction, wherein solvent is: THF, acetonitrile, methylene dichloride, ethylene dichloride, ether, isopropyl ether, methyl tertiary butyl ether, toluene, dimethylbenzene, ethyl acetate, methyl alcohol, ethanol, Virahol etc., temperature of reaction is 0～200 ℃.Below with R
1=3,5-dimephenyl, R
2=Cl, 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.
(0.487 g, 1.000 mol) are dissolved in the 20 mL methyl alcohol with compound (2), add sodium borohydride (19.210 g again, 1.000 mol), back flow reaction 1 h, cooling, reaction solution is poured in the water, and ethyl acetate extraction (3 * 50 mL) merges organic layer, the saturated common salt washing is (50 mL) once, anhydrous sodium sulfate drying, the concentrating under reduced pressure solvent gets crude product, and ethyl alcohol recrystallization is once, get white solid 0.450 g, yield 92%;
N-[4-(Aminosulfonyl)-2-methylphenyl]-2-([4-chloro-2-(3,5-dimebenzoyl)aminophenoxy]acetamide?(109).
Yield?92%;?white?solid,?mp?198.9-199.7℃;?
1H?NMR?(DMSO-
d 6)?
δ?(ppm):?2.19?(s,?6H,?2C
H 3 ),?2.24?(s,?3H,?C
H 3 ),?4.79?(q,?2H,?C
H 2 ),?5.89?(d,?1H,?
J?=?4.4?Hz,?O
H),?6.05?(d,?1H,?
J?=?3.6?Hz,?C
H),?7.30?(s,?2H,?N
H 2 ),?6.81-7.73?(m,?9H,?Ph
H),?9.49?(s,?1H,?N
H);?
13C?NMR?(DMSO-
d 6 )?
δ:?17.7,?21.0?(2C),?67.6,?68.1,?114.1,?123.8,?124.2?(2C),?124.4,?125.2,?126.7,?127.5,?127.7,?128.3,?131.8,?136.3,?136.9?(2C),?138.6,?140.6,?144.2,?153.0,?166.6;?MS?(ESI)?
m/z?487?(M
+?-?H);?Anal.?(C
24H
25ClN
2O
5S)?C,?H,?Cl,?N,?S,?O.
N-[4-(Aminosulfonyl)-2-methylphenyl]-2-([4-chloro-2-(2,3-dimebenzoyl)aminophenoxy]acetamide?(MXD112).
Yield?98.9%;?white?solid,?mp?173.4-174.3℃;?
1H?NMR?(DMSO-
d 6)?
δ?(ppm):?2.15?(s,?3H,?C
H 3 ),?2.18?(s,?3H,?C
H 3 ),?2.23?(s,?3H,?C
H 3 ),?4.83?(q,?2H,?C
H 2 ),?5.83?(s,?1H,?O
H),?6.33?(s,?1H,?C
H),?7.33?(s,?2H,?N
H 2 ),?7.01-7.71?(m,?9H,?Ph
H),?9.65?(s,?1H,?N
H);?
13C?NMR?(DMSO-
d 6 )?
δ:?14.5,?17.9,?20.2,?65.5,?67.7,?114.1,?123.7,?123.8,?124.4,?124.6,?125.0?(2C),?127.4,?127.7?(2C),?128.6,?133.8,?136.6,?138.2,?138.6,?140.6,?141.5,?153.6,?166.8;?MS?(ESI)?
m/z?487?(M
+?-?H);?Anal.?(C
24H
25ClN
2O
5S)?C,?H,?Cl,?N,?S,?O.
N-[4-(Aminosulfonyl)-2-methylphenyl]-2-([4-chloro-2-(2,4-dimebenzoyl)aminophenoxy]acetamide?(MXD111).
Yield?97.8%;?white?solid,?mp?185.4-186.3℃;?
1H?NMR?(DMSO-
d 6)?
δ?(ppm):?2.10?(s,?6H,?2C
H 3 ),?2.25?(s,?3H,?C
H 3 ),?4.78?(q,?2H,?C
H 2 ),?5.78?(s,?1H,?O
H),?6.32?(s,?1H,?C
H),?7.27?(s,?2H,?N
H 2 ),?6.92-7.70?(m,?9H,?Ph
H),?9.45?(s,?1H,?N
H);?
13C?NMR?(DMSO-
d 6 )?
δ:?17.8,?18.8,?20.6,?66.2,?67.7,?114.0,?123.8,?124.5,?125.1,?126.2,?126.6,?127.3,?127.7?(2C),?130.8,?132.0,?135.1,?135.5,?135.9,?138.6,?138.7,?140.6,?153.6,?166.7;?MS?(ESI)?
m/z?487?(M
+?-?H);?Anal.?(C
24H
25ClN
2O
5S)?C,?H,?Cl,?N,?S,?O.
N-[4-(Aminosulfonyl)-2-methylphenyl]-2-([4-chloro-2-(2,4-dichlorobenzoyl)aminophenoxy]acetamide?(MXD111).
Yield?96.7%;?white?solid,?mp?198.7-199.8℃;?
1H?NMR?(DMSO-
d 6)?
δ?(ppm):?2.27?(s,?3H,?C
H 3 ),?4.84?(d,?2H,?
J?=?4.8?Hz,?C
H 2 ),?6.13?(d,?1H,?
J?=?4.4?Hz,?O
H),?6.29?(d,?1H,?
J?=?4.4?Hz,?C
H),?7.29?(s,?2H,?N
H 2 ),?7.27-7.74?(m,?9H,?Ph
H),?9.87?(s,?1H,?N
H);?
13C?NMR?(DMSO-
d 6 )?
δ:?17.8,?67.1,?67.5,?114.1,?123.7,?124.4,?125.1?(2C),?125.3,?126.4,?126.5,?127.9,?128.1,?131.8,?133.8?(2C),?134.7,?138.6,?140.5,?148.7,?152.9,?166.5;?MS?(ESI)?
m/z?528?(M
+?-?H);?Anal.?(C
22H
19Cl
3N
2O
5S)?C,?H,?Cl,?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.
| Compd | Ar | EC 50(μM) a | CC 50 (nM) b | SI c |
| MXD108 | 2,5-diMe-Ph | 37.3 | 1.0 | 36.1 |
| MXD109 | 3,5-diMe-Ph | 30.3 | 0.2 | 134.0 |
| MXD110 | 2.3-diMe-Ph | 227.5 | ＞4.1 | ＜55.6 |
| MXD111 | 2.4-diMe-Ph | 28.5 | ＞4.1 | ＜7.0 |
| MXD112 | 3,5-diCl-Ph | 14.2 | 1.4 | 10.5 |
| MXD122 | 4-Me-Ph | 38.5 | 0.4 | 95.9 |
| 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 50% in C8166 cells.
bCC
50: cytotoxic concentration of compound that reduces the normal uninfected C8166 cellviability by 50%.
cSI: selectivity index: ratio CC
50/EC
50.。
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 the foregoing description.
Claims (7)
1. benzhydrol derivative is characterized in that having following structural formula:
（
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 diarylcarbinols compounds as claimed in claim 1 is characterized in that the reaction formula for preparing is as follows:
In the above-mentioned reaction formula, the compound of structural formula shown in (2) (
2)The ketone carbonyl be reduced to hydroxyl, promptly make target compound.
3. preparation method as claimed in claim 2 is characterized in that reductive condition is Pt, the hydrogenation of Ni metal catalytic, borane reagent reduction, pure aurin tricarboxylic acid reduction, sodium borohydride or potassium borohydride reduction; Wherein solvent is THF, acetonitrile, methylene dichloride, ethylene dichloride, ether, isopropyl ether, methyl tertiary butyl ether, toluene, dimethylbenzene, ethyl acetate, methyl alcohol, ethanol or Virahol, and temperature of reaction is 0～200 ℃.
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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100995779A CN102212022A (en) | 2011-04-20 | 2011-04-20 | Diphenyl methanol derivatives and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100995779A CN102212022A (en) | 2011-04-20 | 2011-04-20 | Diphenyl methanol derivatives and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102212022A true CN102212022A (en) | 2011-10-12 |
Family
ID=44743590
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100995779A Pending CN102212022A (en) | 2011-04-20 | 2011-04-20 | Diphenyl methanol derivatives and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102212022A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1391565A (en) * | 1999-09-04 | 2003-01-15 | 葛兰素集团有限公司 | Benzophenones as inhibitors of reverse transcriptase |
| CN1494528A (en) * | 2001-03-02 | 2004-05-05 | ʷ��˿�������ȳ�ķ����˾ | Benzophenones as inhibitors of reverse transcriptase |
| WO2006012733A1 (en) * | 2004-08-02 | 2006-02-09 | Boehringer Ingelheim International Gmbh | Benzoic acid derivatives as non-nucleoside reverse transcriptase inhibitors |
-
2011
- 2011-04-20 CN CN2011100995779A patent/CN102212022A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1391565A (en) * | 1999-09-04 | 2003-01-15 | 葛兰素集团有限公司 | Benzophenones as inhibitors of reverse transcriptase |
| CN1494528A (en) * | 2001-03-02 | 2004-05-05 | ʷ��˿�������ȳ�ķ����˾ | Benzophenones as inhibitors of reverse transcriptase |
| WO2006012733A1 (en) * | 2004-08-02 | 2006-02-09 | Boehringer Ingelheim International Gmbh | Benzoic acid derivatives as non-nucleoside reverse transcriptase inhibitors |
Non-Patent Citations (2)
| Title |
|---|
| DE SERRES, MARK等: "The disposition and metabolism of GW695634: A non-nucleoside reverse transcriptase inhibitor (NNRTi) for treatment of HIV/AIDS", 《XENOBIOTICA》 * |
| WYATT, PAUL G.等: "Benzophenone Derivatives: A Novel Series of Potent and Selective Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8921388B2 (en) | Dihydroxypyrimidine carbonic acid derivatives and their use in the treatment, amelioration or prevention of a viral disease | |
| WO2008132138A1 (en) | Derivatives of 4,6-disubstituted aminopyrimidines | |
| AU2016382372B2 (en) | Sulfonamide derivative and preparation method and use thereof | |
| CN101121698B (en) | Diarylmiazines derivatives, preparation method and use thereof | |
| JP5404607B2 (en) | Aniline derivative having anti-RNA virus action | |
| Fan et al. | Discovery of 5, 6-dihydro-indolo [1, 2-a] quinoxaline derivatives as new HIV-1 inhibitors in vitro | |
| CN101463014B (en) | Diaryl benzo pyridine derivative, and its pharmaceutical composition and use thereof | |
| AU2012300274B2 (en) | HIV replication inhibitors | |
| WO2017046318A1 (en) | Triazolones derivatives for use in the treatment, amelioration or prevention of a viral disease | |
| Asirvatham et al. | Privileged Scaffold Possessing Diverse Bioactivity Profile | |
| US9328084B2 (en) | Nitrogen-containing biphenyl compounds, pharmaceutical compositions of same, preparation methods and anti-HIV-1 uses thereof | |
| CN103732575A (en) | Diarylaniline or diarylpyridinamine compound and preparation method and medical use thereof | |
| CA2531766C (en) | Entry inhibitors of the hiv virus | |
| 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 | |
| WO2013137456A1 (en) | Antivirus composition | |
| CN102212022A (en) | Diphenyl methanol derivatives and preparation method and application thereof | |
| CN101723903A (en) | 4-carbonyl diaryl pyridine derivatives as well as preparation methods and applications thereof | |
| ES2833473T3 (en) | Purinyl-N-hydroxyl pyrimidine formamide derivatives, method of preparation and use thereof | |
| CN101759684A (en) | Diaryl pyrimidine derivative, preparation method and use thereof | |
| CN103360315A (en) | Heterocyclic aryloxyacetyl hydrazone derivative and its preparation method and application thereof | |
| CN102219717A (en) | N-phenyl aryl formamide derivative, preparation method thereof and use thereof | |
| KR102297433B1 (en) | Substituted pyridine-piperazinyl analogues as rsv antiviral compounds | |
| CN102206177A (en) | 1-naphthyl benzophenone derivatives, and preparation method and application thereof | |
| CA3055509A1 (en) | Novel benzimidazolone compound and pharmaceutical use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20111012 |