- Preparation method of lopinavir
-
The invention provides a preparation method represented by formula (I) shown in the specification, and particularly provides a preparation method of (2S)-N-{(1S, 3S, 4S)-1-benzyl-4-[2-(2, 6-dimethylphenoxy)acetamido]-3-hydroxy-5-phenylamyl}-3-methyl-2-(2-oxotetrahydropyrimidin-1-yl)butyramide. The novel method is provided for preparing lopinavir.
- -
-
Paragraph 0004; 0007; 0008; 0010
(2021/10/05)
-
- Synthesis and characterization of novel analogues of lopinavir
-
The present work describes the identification, origin, synthesis, characterization and control of four novel analogues of lopinavir viz. leucine analogue of lopinavir, isoleucine analogue of lopinavir, methyl analogue of lopinavir and dihydroxy analogue of lopinavir.
- Reddy, Peketi Rajesh,Musunuri, Sivanadh,Ramasekhara Reddy,Subrahmanyam Chittala,Murthy,Krishnamohan
-
p. 151 - 158
(2021/01/06)
-
- Novel crystal form of lopinavir and preparation method thereof
-
The invention discloses a novel crystal form of lopinavir and a preparation method thereof, belonging to the technical field of medicine crystal forms. According to the invention, lopinavir is prepared, and the novel crystal form of lopinavir is cultured; a real stereo structure of four chiral centers in a lopinavir molecule can be seen from an obtained single crystal structure; crystal data is recorded by a crystal database, namely CCDC 1969375, of the British Cambridge University for the first time; and compared with other detection methods reported at present, an X-ray single crystal diffraction method is the most direct and intuitive method for determining the absolute configuration and space structure of lopinavir.
- -
-
-
- Novel method for preparing lopinavir
-
The invention relates to a novel method for preparing lopinavir (I), a condensation reaction of a compound shown in a formula (II) and a compound shown in a formula (III) is carried out at room temperature under mild condensation reaction conditions, and heating or cooling is not needed; the preparation method does not need special chemical reagents, the special chemical reagents are solvents andreagents commonly used in laboratories, the total yield is higher than 85%, preferably higher than 90%, in some embodiments, the yield reaches 96%, and the preparation method is especially suitable for industrial production.
- -
-
Paragraph 0064-0067; 0082-0085
(2020/05/01)
-
- Preparation of lopinavir by one-pot method
-
The invention relates to preparation of lopinavir as shown in formula (I) by a one-pot method. 2, 6-dimethylphenoxyacetic acid, a carboxyl activator and a compound as shown in a formula (III) are subjected to a condensation reaction in an organic solvent under a mild condensation reaction condition, the reaction can be carried out at room temperature without heating or cooling. The preparation method does not need special chemical reagents, and the solvent and the reagents used in the method are commonly used in laboratories. The total yield is higher than 85%, preferably higher than 90%, andthe yield reaches 96% in some embodiments. The preparation method is especially suitable for industrial production.
- -
-
Paragraph 0072-0077
(2020/04/02)
-
- AN IMPROVED PROCESS FOR PREPARATION OF LOPINAVIR AND ITS INTERMEDIATES THEREOF
-
The present invention generally relates to an improved process for preparation of lopinavir and its intermediates through formation of tartrate salt of compound of Formula (III).
- -
-
Page/Page column 22; 24-25
(2019/10/23)
-
- Method used for preparing Lopinavir using one-pot method
-
The invention discloses a method used for preparing lopinavir using one-pot method. According to the method, under certain organic solvent conditions, (2S)-(1-Tetrahydropyramid-2-one)-3-methylbutanoicacid is reacted with thionyl chloride so as to obtain (2S)-(1-Tetrahydropyramid-2-one)-3-methyl butyryl chloride; a weak base acid binding agent and N-[(1S,2S,4S)-4-amino-2-hydroxy-5-phenyl-1-(phenylmethyl)pentyl]-2-(2,6-dimethylphenoxy)acetamide are added into an obtained reaction system for amidation reaction; after amidation reaction, an obtained product is subjected to post-treatment so as toobtain lopinavir finished product. According to the method, on-pot method is adopted, the process is simple, production period is short, the finial products can be separated and purified easily, synthesis yield is high, the method is economical and is high in feasibility, and is suitable for industrialized production.
- -
-
Paragraph 0014
(2018/07/30)
-
- NOVEL POLYMORPHS OF LOPINAVIR
-
The present invention provides a novel cyclohexane solvate form of lopinavir, and a process for its preparation thereof. The present invention also provides a novel desolvated crystalline form of lopinavir, process for its preparation and to pharmaceutical composition containing it. Thus, for example, lopinavir cyclohexane solvate was heated at 100° C. for 10 hours to give lopinavir desolvated crystalline form H1.
- -
-
Page/Page column 3
(2011/12/13)
-
- PROCESS FOR THE PREPARATION OF SUBSTANTIALLY PURE (2S,3S,5S)-5-AMINO-2-N,N-DIBENZYLAMINO-3-HYDROXY-1,6-DIPHENYLHEXANE
-
The present invention relates to the purification of (2S,3S,5S)-5-amino-2-N,N-dibenzylamino-3-hydroxy-1,6-diphenylhexane (III) by making its crystalline acid addition salt, which can be used as such to produce Lopinavir/Ritonavir with high purity and yield. Formula III
- -
-
Page/Page column 5
(2010/12/29)
-
- NOVEL POLYMORPHS OF LOPINAVIR
-
The present invention provides a novel cyclohexane solvate form of lopinavir, and a process for its preparation thereof. The present invention also provides a novel desolvated crystalline form of lopinavir, process for its preparation and to pharmaceutical composition containing it. Thus, for example, lopinavir cyclohexane solvate was heated at 100 °C for 10 hours to give lopinavir desolvated crystalline form H1.
- -
-
Page/Page column 7
(2010/08/18)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF SUBSTANTIALLY PURE (2S,3S,5S)-5-AMINO-2-N,N-DIBENZYLAMINO-3-HYDROXY-1,6-DIPHENYLHEXANE
-
The present invention relates to the purification of (2S,3S,5S)-5-amino-2-N,N-dibenzylamino-3-hydroxy-1,6-diphenylhexane (III) by making its crystalline acid addition salt, which can be used as such to produce Lopinavir /Ritonavir with high purity and yield. Formula III
- -
-
Page/Page column 12; 15
(2009/01/24)
-
- A PROCESS FOR THE SYNTHESIS OF 2-AMINO-5-PROTECTED AMINO-3-HYDROXY-1, 6-DIPHENYLHEXANE OR A SALT THEREOF - AN INTERMEDIATE FOR ANTIVIRAL DRUGS
-
The present invention relates to an improved process for preparing 2-amino-5-protected-amino-3-hydroxy-1,6-diphenylhexane compounds or acid addition salts thereof, which can be useful intermediates for preparing compounds with antiviral activity. The present invention further provides a process for preparing HIV protease inhibitors, lopinavir and ritonavir.
- -
-
Page/Page column 21-22
(2008/06/13)
-
- PROCESSES FOR THE PREPARATION OF LOPINAVIR AND ITS INTERMEDIATE - (S)-TETRAHYDRO-ALPHA-(1-METHYLETHYL)-2-OXO-1(2H)-PYRIMIDINEACETIC ACID
-
The invention relates to processes for the preparation of (S)-tetrahydro-alpha-(1-methylethyl)-2-oxo-1(2H)-pyrimidineacetic acid or a salt thereof, and to use of this compound as intermediate for the preparation of compounds with antiviral activity. The invention also relates to a process for the preparation of lopinavir, and pharmaceutical compositions that include the lopinavir.
- -
-
Page/Page column 10-11
(2010/11/24)
-
- Novel lopinavir analogues incorporating heterocyclic replacements of six-member cyclic urea - Synthesis and structure-activity relationships
-
The HIV protease inhibitor ABT-378 (lopinavir) has a six-member cyclic urea in the P-2 position. A series of analogues in which the six-member cyclic urea is replaced by various heterocycles was synthesized and the structure-activity relationships explored.
- Sham, Hing L.,Betebenner, David A.,Rosenbrook, William,Herrin, Thomas,Saldivar, Ayda,Vasavanonda, Sudthida,Plattner, Jacob J.,Norbeck, Daniel W.
-
p. 2643 - 2645
(2007/10/03)
-
- Processes and intermediates for preparing retroviral protease inhibitors
-
The instant invention provides processes and intermediates employed in the synthesis of ((2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)-amino-3-hydroxy-5-(2S-(1-tetrahydropyrimid-2-onyl)-3-methyl-butanoyl)amino-1,6-diphenylhexane and analogs thereof.
- -
-
-
- Retroviral protease inhibiting compounds
-
A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.
- -
-
-
- Novel Lopinavir analogues incorporating non-Aromatic P-1 side chains - Synthesis and structure-activity relationships
-
The HIV protease inhibitor Lopinavir has a pseudosymmetric core unit incorporating benzyl groups at both P-1, P-1′ positions. A series of analogues incorporating non-aromatic side chains at the P-1 position were synthesized and the structure-activity relationships explored.
- Sham, Hing L.,Zhao, Chen,Li, Leping,Betebenner, David A.,Saldivar, Ayda,Vasavanonda, Sudthida,Kempf, Dale J.,Plattner, Jacob J.,Norbeck, Daniel W.
-
p. 3101 - 3103
(2007/10/03)
-
- Crystalline pharmaceutical
-
New crystalline forms of lopinavir are disclosed.
- -
-
-
- Synthesis of HIV protease inhibitor ABT-378 (lopinavir)
-
A large scale process for the synthesis of HIV protease inhibitor candidate ABT-378 has been developed which utilizes an intermediate common to the synthesis of ritonavir, Abbott's first generation compound. The synthesis relies on the sequential acylation of this intermediate which is carried through as a mixture of diastereomers until the penultimate step. A synthesis of acid 5, derived from L-valine, is also reported.
- Stoner, Eric J.,Cooper, Arthur J.,Dickman, Daniel A.,Kolaczkowski, Lawrence,Lallaman, John E.,Liu, Jih-Hua,Oliver-Shaffer, Patricia A.,Patel, Ketan M.,Paterson Jr., Joseph B.,Plata, Daniel J.,Riley, David A.,Sham, Hing L.,Stengel, Peter J.,Tien, Jien-Heh J.
-
p. 264 - 269
(2013/09/07)
-
- Synthesis of ABT-378, an HIV protease inhibitor candidate: Avoiding the use of carbodiimides in a difficult peptide coupling
-
An alternative to carbodiimide-mediated peptide coupling protocols has been developed for a carboxylic acid prone to decomposition by polymerization. This method, involving the in situ generation of an acyl imidazolide, has been applied to the preparation of a lead clinical HIV protease inhibitor candidate, ABT-378. The nature of the polymerization and optimization of the new reaction conditions are presented.
- Stoner, Eric J.,Stengel, Peter J.,Cooper, Arthur J.
-
p. 145 - 148
(2013/09/08)
-
