- Anti-HIV medicine containing indinavir and preparation method thereof
-
The invention discloses anti-HIV medicine containing indinavir and a preparation method thereof. The anti-HIV medicine containing indinavir is prepared from indinavir and pharmaceutically acceptable carriers, wherein the chemical name of indinavir is (1(1S,2R),5(S))-2,3,5-tri-deoxy-N-(2,3-dihydro-2-hydroxyl-1H-indene-1-yl)-5-[2-[[(1,1-dimethyl ethyl) amino]carbonyl]-4-(3-picolyl)-1-piperazinyl]-2-(benzyl)-D-erythro-valeramide. The process of a preparation process is simple and compact; the raw materials can be easily obtained; economic performance and environment protection are realized; the industrialization can be favorably realized; the economic technology development of the indinavir raw medicine of the anti-HIV medicine can be promoted; the dissolving-out degree of the anti-HIV medicine containing indinavir is high; the effect is ideal; the medicine is suitable for mass production.
- -
-
Paragraph 0017
(2018/08/28)
-
- Methods for predicting the response to statins
-
The invention provides methods for optimizing therapeutic efficacy for treating hypercholesterolemia in a subject having a cardiovascular disease (CVD), comprising (a) determining subject characteristics that affect the likelihood of reaching a goal level of low density lipoprotein (LDL); and (b) obtaining success probabilities of a variety of statin treatments for reaching said goal level of LDL using said subject characteristics and a multivariate model; and (c) administrating the optimal statin treatment with the highest success probability of step (b) to said subject thereby optimizing therapeutic efficacy for treating hypercholesterolemia in said subject.
- -
-
-
- Reductive alkylation of saturated cyclic amines
-
Saturated cyclic amines (e.g., piperazines and piperidines) are reductively alkylated with an N-containing heteroaryl carbaldehyde using an alkylcarboxylic acid and a borohydride to obtain a product comprising an N-((N-containing heteroaryl)methyl)-substituted cyclic amine and one or more borane complexes thereof, after which the product is treated with a catalytic amount of a Pt or Pd catalyst in the presence of an alcohol to cleave the borane complex(es) and thereby afford the N-((N-containing heteroaryl)methyl)cyclic amine free of borane complex. Saturated cyclic amines are also reductively alkylated by adding an N-containing heteroaryl carbaldehyde and the amine to a tetrahydroborate salt-alkylcarboxylic acid-solvent admixture and aging the resulting reaction mixture to obtain an alkylated product substantially free of borane complex.
- -
-
-
- Asymmetric synthesis of chiral organofluorine compounds: Use of nonracemic fluoroiodoacetic acid as a practical electrophile and its application to the synthesis of monofluoro hydroxyethylene dipeptide isosteres within a novel series of HIV protease inhibitors
-
Two stereoselective routes to a series of diastereomeric inhibitors of HIV protease, monofluorinated analogues of the Merck HIV protease inhibitor indinavir, are described. The two routes feature stereoselective construction of the fluorinated core subunits by asymmetric alkylation reactions. The first-generation syntheses were based on the conjugate addition of the lithium enolate derived-from pseudoephedrine α-fluoroacetamide to nitroalkene 12, a modestly diastereoselective transformation. A more practical second-generation synthetic route was developed that is based on a novel method for the asymmetric synthesis of organofluorine compounds, by enolate alkylation using optically active fluoroiodoacetic acid as the electrophile in combination with a chiral amide enolate. Resolution of fluoroiodoacetic acid with ephedrine provides either enantiomeric form of the electrophile in ≥96% ee. Alkylation reactions with this stable and storable chiral fluorinated precursor are shown to proceed in a highly stereospecific manner. With the development of substrate-controlled syn- or anti-selective reductions of α-fluoro ketones 44 and 45 (diastereomeric ratios 12:1-84:1), efficient and stereoselective routes to each of the four targeted inhibitors were achieved. The optimized synthetic route to the most potent inhibitor (syn,syn-4, Ki = 2.0 nM) proceeded in seven steps (87% average yield per step) from aminoindanol hydrocinnamide 40 and (S)-fluoroiodoacetic acid, and allowed for the preparation of more than 1 g of this compound. The inhibition of HIV-1 protease by each of the fluorinated inhibitors was evaluated in vitro, and the variation of potency as a function of inhibitor stereochemistry is discussed.
- Myers,Barbay,Zhong
-
p. 7207 - 7219
(2007/10/03)
-
- Combinatorial diversification of indinavir: In vivo mixture dosing of an HIV protease inhibitor library
-
An efficient combination solution-phase/solid-phase route enabling the diversification of the P1', P2', and P3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Rano, Thomas A.,Cheng, Yuan,Huening, Tracy T.,Zhang, Fengqi,Schleif, William A.,Gabryelski, Lori,Olsen, David B.,Kuo, Lawrence C.,Lin, Jiunn H.,Xu, Xin,Olah, Timothy V.,McLoughlin, Debra A.,King, Richard,Chapman, Kevin T.,Tata, James R.
-
p. 1527 - 1530
(2007/10/03)
-
- HIV protease inhibitors useful for the treatment of AIDS
-
Compounds of formula STR1 where R1 and R2 are independently hydrogen or optionally-substituted C1-4 alkyl or aryl, or R1 and R2 are joined together to form a monocyclic or bicyclic ring system, are HIV protease inhibitors. These compounds are useful in the treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of treating infection by HIV are also described.
- -
-
-
- Highly Diastereoselective Reaction of a Chiral, Non-Racemic Amide Enolate with (S)-Glycidyl Tosylate. Synthesis of the Orally Active HIV-1 Protease Inhibitor L-735,524
-
Reaction of chiral amide enolate Li-1 with (S)-glycidyl tosylate 11 affords the epoxide 3 in 72percent yield with high diastereoselectivity.Epoxide 3 is converted to the orally-active HIV-1 protease inhibitor L-735,524 in 71percent isolated yield.
- Askin, David,Eng, Kan K.,Rossen, Kai,Purick, Robert M.,Wells, Kenneth M.,et al.
-
p. 673 - 676
(2007/10/02)
-
- L-735,524: The design of a potent and orally bioavailable HIV protease inhibitor
-
A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into the backbone of the L-685,434 (2) series provided antiviral potency combined with a highly improved pharmacokinetic profile in animal models. Guided by molecular modeling and an X-ray crystal structure of the inhibited enzyme complex, we were able to design L-735,524. This compound is potent and competitively inhibits HIV-1 PR and HIV-2 PR with K(i) values of 0.52 and 3.3 nM, respectively. It also stops the spread of the HIV-1(IIIb)-infected MT4 lymphoid cells at concentrations of 25-50 nM. To date, numerous HIV-PR inhibitors have been reported, but few have been studied in humans because they lack acceptable oral bioavailability. L-735,524 is orally bioavailable in three animals models, using clinically acceptable formulations, and is currently in phase II human clinical trials.
- Dorsey,Levin,McDaniel,Vacca,Guare,Darke,Zugay,Emini,Schleif,Quintero,Lin,Chen -,Holloway,Fitzgerald,Axel,Ostovic,Anderson,Huff
-
p. 3443 - 3451
(2007/10/02)
-
