化合物信息

ID:1132

基本信息

化学结构

分子式

C₂₇H₃₇N₃O₇S

分子量

547.66358

精确质量

547.23522154

电荷

InChI

InChI=1S/C27H37N3O7S/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32)/t22-,23-,24+,25-,26+/m0/s1

InChIKey

CJBJHOAVZSMMDJ-HEXNFIEUSA-N

Canonic Smiles

CC(CN(S(=O)(=O)c1ccc(cc1)N)C[C@H]([C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@@H]2[C@H]1CCO2)O)C

Isomeric Smiles

S(=O)(=O)(N(C[C@@H](O)[C@@H](NC(=O)O[C@@H]1[C@H]2[C@@H](OC1)OCC2)Cc1ccccc1)CC(C)C)c1ccc(N)cc1

计算属性

JChem

LogD (pH = 7.4)

2.82

LogD (pH = 5.5)

2.82

Log P

2.82

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

false

Acid pKa

2.39

极化表面积

140.42

极化性

57.24

摩尔折射率

142.34

LOG S

-4.77

数据来源

学术数据

产品目录

数据来源

名称和标识

别名

TMC-114Darunavirum [INN-latin]AIDS073035TMC114DarunavirUIC-94017[(1S,2R)-3-[[(4-Aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenyl-methyl)propyl]carabamic Acid (3R,3aS,6aR)-Hexahydrofuro[2,3-b]-furan-3-yl EsterTMC114(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE(3R,3aS,6aR)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-neopentylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate{(1S,2R)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester(3R,3aS,6aR)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamatedarunavirDarunavir(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N(1)-isobutylsulfanilamido)propyl)carbamateN-((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-benzylpropyl)((1S,2R,5R)-4,6-dioxabicyclo(3.3.0)oct-2-yloxy)carboxamide[(S)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-1-((R)-phenylmethyl)-propyl]-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester

IUPAC标准名

(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)-4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate

商标名

Prezista

IUPAC传统名

(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate darunavir

国际非专利药品(INN)

darunavirumdarunavir

名称和标识

数据登录号

PubChem SID

4650690816096459587351130

PubChem CID

213039

CAS号

206361-99-1

MetaboLights数据库

MTBLS1918MTBLS2633

Drug Central Database

4,143

CHEBI ID

CHEBI:367163CHEBI:39487CHEBI:589942

PDBeChem数据库

017

Reaxys Registry

7960555

ACToR数据库

618109-00-5206361-99-1

BRENDA Ligand数据库

190123670164284164283

PubMed文献链接

250176821577142716480273

BRENDA数据库

3.4.17.233.4.23.493.4.23.167.6.2.23.4.24.843.4.23.47

BindingDB数据库

8125

BKMS React数据库

164284164283190123670

DrugBank ID

Beilstein号

CHEMBL

KEGG DRUG Database

SureChEMBL数据库

CompTox数据库

维基百科标题

数据登录号

化合物性质

理化性质

溶解度

Approximately 0.15 mg/mL at 20°C as ethanolate salt

Methanol

Chloroform

疏水性(logP)

1.8

外观

Off-White to Pale Yellow Solid

熔点

130-132°C

安全信息

-20°C Freezer

下载链接

产品相关信息

下载链接

化合物性质

分子相关蛋白质

分子图谱

暂无数据

点击上传数据

描述信息

DrugBank

DB01264

Drug Groups

approved

Description

Darunavir is a protease inhibitor used to treat HIV. It acts on the HIV aspartyl protease which the virus needs to cleave the HIV polyprotein into its functional fragments.

Indication

Darunavir, co-administered with ritonavir, and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.

Pharmacology

Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006). Darunavir is used as an adjunct therapy with low dose ritonavir, which inhibits cytochrome P450 3A (CYP3A) which increases the bioavailability and half life of darunavir.

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Hepatic. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.

Absorption

The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.

Half Life

The terminal elimination half-life of darunavir was approximately 15 hours when combined with ritonavir.

Protein Binding

Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).

Elimination

Darunavir is primarily metabolized by CYP3A. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A. A mass balance study in healthy volunteers showed that after single dose administration of 400 mg 14C-darunavir, co-administered with 100 mg ritonavir, approximately 79.5% and 13.9% of the administered dose of 14C-darunavir was recovered in the feces and urine, respectively.

Clearance

* 32.8 L/hr [Healthy volunteers receiving intravenous administration of 400 mg of darunavir]
* 5.9 L/hr [Healthy volunteers receiving intravenous administrations of 400 mg of darunavir and 100 mg of ritonavir twice daily]

References

• Back D, Sekar V, Hoetelmans RM: Darunavir: pharmacokinetics and drug interactions. Antivir Ther. 2008;13(1):1-13. [Pubmed]

• Medilexicon [Link]

• Company Website [Link]

• Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [Pubmed]

• Koh Y, Matsumi S, Das D, Amano M, Davis DA, Li J, Leschenko S, Baldridge A, Shioda T, Yarchoan R, Ghosh AK, Mitsuya H: Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. J Biol Chem. 2007 Sep 28;282(39):28709-20. Epub 2007 Jul 17. [Pubmed]

• Kovalevsky AY, Tie Y, Liu F, Boross PI, Wang YF, Leshchenko S, Ghosh AK, Harrison RW, Weber IT: Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. J Med Chem. 2006 Feb 23;49(4):1379-87. [Pubmed]

• De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP: TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005 Jun;49(6):2314-21. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

TRC

D193500

Second generation HIV-1-protease inhibitor; structurally similar to amprenavir. Antiviral.

ChEBI

CHEBI:367163

An N,N-disubstituted benzenesulfonamide bearing an unsubstituted amino group at the 4-position, used for the treatment of HIV infection. A second-generation HIV protease inhibitor, darunavir was designed to form robust interactions with the protease enzyme from many strains of HIV, including those from treatment-experienced patients with multiple resistance mutations to other protease inhibitors.

描述信息

参考文献

PubChem文献

数据源提供

• Medilexicon Link

• Back D, Sekar V, Hoetelmans RM: Darunavir: pharmacokinetics and drug interactions. Antivir Ther. 2008;13(1):1-13. Pubmed

• Company Website Link

• Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. Pubmed

• Surleraux, D.L.N.G., et al.: J. Med. Chem., 48, 1813 (2003)

• Koh, Y., et al.: Antimicrob. Agents Chemother., 47, 3123 (2003)

• Arasteh, K., et al.: AIDS, 19, 943 (2003)

参考文献

生物活性

PubChem BioAssay

生物活性

导航

基本信息

计算属性

• RDKit

• JChem

数据来源

• 学术数据

• 产品目录

名称和标识

• 别名

• IUPAC标准名

• 商标名

• IUPAC传统名

• 国际非专利药品(INN)

名称和标识

数据登录号

• PubChem SID

• PubChem CID

• CAS号

• PDB数据库

• MetaboLights数据库

• Drug Central Database

• CHEBI ID

• PDBeChem数据库

• Reaxys Registry

• ACToR数据库

• BRENDA Ligand数据库

• PubMed文献链接

• BRENDA数据库

• BindingDB数据库

• BKMS React数据库

• DrugBank ID

• Beilstein号

• CHEMBL

• KEGG DRUG Database

• SureChEMBL数据库

• CompTox数据库

• 维基百科标题

数据登录号

化合物性质

• 理化性质

• 安全信息

• 产品相关信息

分子相关蛋白质

• PDB Bank

分子图谱

描述信息

• DrugBank

• TRC

• ChEBI

描述信息

参考文献

• PubChem文献

• 数据源提供

生物活性

• PubChem BioAssay

产品目录

TRC

D193500

别名

IUPAC标准名

IUPAC传统名

(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate darunavir

国际非专利药品(INN)

darunavirumdarunavir

MetaboLights数据库

MTBLS1918MTBLS2633

Drug Central Database

4,143

PDBeChem数据库

017

Reaxys Registry

7960555

ACToR数据库

618109-00-5206361-99-1

BRENDA Ligand数据库

190123670164284164283

PubMed文献链接

250176821577142716480273

BindingDB数据库

8125

BKMS React数据库

164284164283190123670

Beilstein号

KEGG DRUG Database

SureChEMBL数据库

CompTox数据库

维基百科标题

数据源提供

• Medilexicon Link

• Back D, Sekar V, Hoetelmans RM: Darunavir: pharmacokinetics and drug interactions. Antivir Ther. 2008;13(1):1-13. Pubmed

• Company Website Link

• Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. Pubmed

• Surleraux, D.L.N.G., et al.: J. Med. Chem., 48, 1813 (2003)

• Koh, Y., et al.: Antimicrob. Agents Chemother., 47, 3123 (2003)

• Arasteh, K., et al.: AIDS, 19, 943 (2003)

理化性质

溶解度

Approximately 0.15 mg/mL at 20°C as ethanolate salt

Methanol

Chloroform

疏水性(logP)

1.8

外观

Off-White to Pale Yellow Solid

熔点

130-132°C

安全信息

-20°C Freezer

下载链接

产品相关信息

下载链接

DrugBank

DB01264

Drug Groups

approved

Description

Darunavir is a protease inhibitor used to treat HIV. It acts on the HIV aspartyl protease which the virus needs to cleave the HIV polyprotein into its functional fragments.

Indication

Pharmacology

Affected Organisms

Human Immunodeficiency Virus

Biotransformation

Hepatic. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.

Absorption

The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.

Half Life

The terminal elimination half-life of darunavir was approximately 15 hours when combined with ritonavir.

Protein Binding

Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).

Elimination

Clearance

References

• Back D, Sekar V, Hoetelmans RM: Darunavir: pharmacokinetics and drug interactions. Antivir Ther. 2008;13(1):1-13. [Pubmed]

• Medilexicon [Link]

• Company Website [Link]

• Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

TRC

D193500

Second generation HIV-1-protease inhibitor; structurally similar to amprenavir. Antiviral.

ChEBI

CHEBI:367163