177530-93-7

Usage

Uses

Used in Pharmaceutical Industry:
L 741211 is used as a research tool and drug candidate for the development of treatments targeting neurological and neuropsychiatric disorders. Its ability to selectively block mGluR1 makes it a valuable compound for studying the role of this receptor in various brain functions and diseases.
Used in Neurological Disorders Research:
L 741211 is used as a pharmacological agent to investigate the involvement of mGluR1 in neurological disorders such as Parkinson's disease, Alzheimer's disease, and Huntington's disease. By blocking mGluR1, L 741211 can help researchers understand the underlying mechanisms of these disorders and identify potential therapeutic targets.
Used in Neuropsychiatric Disorders Research:
L 741211 is also used in the study of neuropsychiatric disorders, including anxiety, depression, and schizophrenia. Its antagonistic effect on mGluR1 can provide insights into the role of this receptor in the pathophysiology of these conditions and aid in the development of novel treatment strategies.
Used in Drug Discovery and Development:
L 741211 serves as a lead compound in the design and synthesis of new drugs targeting mGluR1. Its structural features can be modified to create more potent and selective mGluR1 antagonists or allosteric modulators, which can be further optimized for better pharmacokinetic and pharmacodynamic properties.

Upstream product

• 106-47-8 4-chloro-aniline 
• 50893-53-3 carbonochloridic acid 1-chloro-ethyl ester 
• 1262030-21-6 N-(4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)acetamide 
• 1381993-87-8 4-cyclopropyl-2-(2,5-dichlorophenyl)-1,1,1-trifluorobut-3-yn-2-ol 
• 886371-22-8 1-(2,5-dichloro-phenyl)-2,2,2-trifluoroethanone 
• 1381993-89-0 carbamic acid cyclopropyl-(2,5-dichloro-phenyl)-trifluoromethyl-prop-2-ynyl ester 
• 106-46-7 para-dichlorobenzene 
• 201218-10-2 4-cyclopropyl-1,1,1-trifluoro-but-3-yn-2-one 
• 201218-08-8 tert-butyl 4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenylcarbamate 
• 181190-33-0 N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)pivalamide 
• 154598-53-5 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone 
• 65854-91-3 N-(4-chlorophenyl)-2,2-dimethylpropionamide 
• 530-62-1 1,1'-carbonyldiimidazole 
• 168834-43-3 6-amino-3-chloro-α-cyclopropylethynyl-α-(trifluoromethyl)benzyl alcohol 

Downstream Products

• 154801-74-8 (R)-efavirenz 
• 154598-52-4 efavirenz 

Relevant academic research and scientific papers

PROCESS FOR PREPARING EFAVIRENZ

The invention disclosed a 4 step process for the preparation of Efavirenz, starting from 1,4-dichlorobenzene, and its intermediates.

DMP-266 BY CYCLISATION

Disclosed is a method for the preparation of the HIV drug Efavirenz, also known as DMP-266, starting from 1,4-dichlorobenzene, and its intermediates.

PROCESS FOR PREPARATION OF EFAVIRENZ BY CYCLISATION

The invention disclosed a process for the preparation of the HIV drug Efavirenz, also known as DMP-266, starting from 1,4-dichlorobenzene, and its intermediates.

METHODS OF MAKING EFAVIRENZ AND INTERMEDIATES THEREOF

The present invention provides a process for the preparation of Efavirenz. A compound of Formula 1 may be prepared by a process comprising cyclizing, in the presence of a first base, a compound of Formula 5 with a haloformate of Formula 6. Other processes are also provided as well as novel compounds prepared by and used in such processes.

New synthetic technologies for the construction of heterocycles and tryptamines

New synthetic methods for the construction of novel heterocycles and tryptamines are described. Thus, N-Boc anilines (I) are sequentially converted to heterocycles II ((3-(2-aminophenyl)pyrrolidin-3-ol) derivatives),III (substituted 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-pyrrol idines), and VI (2-(4,5-dihydro-1H-pyrrol-3-yl)aniline) derivatives through a route involving t-BuLi induced ortho-metalation/ LaCl3 2LiCl metalexchange, reaction with N-Boc pyrrolidin-3-one (5), and subsequent deca rboxylative fragmentation. Labile intermediates VI are effectively converted to tryptamines Xa and Xb under controlled proticacidconditions.Inadditiontoprovidingexpedientaccesstothe2-oxo- 1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-pyrrolidines (III), the method is applicable to the synthesis of the corresponding 2-oxo-1,2-dihydrospirobenzo[d] [1,3]oxazine-4,3'-piperidine series of spirocycles (e.g., 42) and their precursors (3-(2-aminophenyl)piperidin-3-ol derivatives, e.g., 43) by using N-Boc-protected piperidin-3-one (40). Applications of the developed synthetic technologies to the synthesis of regioisomeric spirocycles 87 and 90, tryptamines 88 and 91, Corey's aspidophytine tryptamine (97), and efavirenz (1) are also described.

Practical synthesis of benzoxazinones useful as HIV reverse transcriptase inhibitors

The present invention describes novel methods for the synthesis of benzoxazinone compounds which are useful as human immunodeficiency virus (HIV) reverse transcriptase inhibitors. The benzoxazinone of the formula: is particularly effective in the treatment of HIV.

4,4-disubstitued-1,4-dihydro-2H-3,1-benzoxazin-2-ones useful as HIV reverse transcriptase inhibitors and intermediates and processes for making the same

The present invention relates to benzoxazinones of formula I: STR1 or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, methods of using the same for treating viral infection or as an assay standard or reagent, and intermediates and processes for making the same.

Synthesis of cyclopropylacetylene

An improved synthesis of cyclopropylacetylene involving cyclization of 5-halo-1-pentyne in strong base is disclosed, and is useful for preparing compounds with a cyclopropylethynyl substituent, such as an intermediate for a highly potent HIV reverse transcriptase inhibitor or other pharmaceutically active compounds.

Benzoxazinones as inhibitors of HIV reverse transcriptase

Certain benzoxazinones are useful in the inhibition of HIV reverse transcriptase (including its resistant varieties), the prevention or treatment of infection by HIV and 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 preventing or treating infection by HIV are also described.

L-743,726 (DMP-266): A novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase

The clinical benefit of the human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) is limited by the rapid selection of inhibitor-resistant vital variants. However, it may he possible to enhance the clinical utility of this inhibitor class by deriving compounds that express both high levels of antiviral activity and an augmented pharmacokinetic profile. Accordingly, we developed a new class of NNRTIs, the 1,4-dihydro-2H-3,1-benzoxazin-2-ones. L-743,726 (DMP-266), a member of this class, was chosen for clinical evaluation because of its in vitro properties. The compound was a potent inhibitor of the wild-type HIV-1 RT (K(i) = 2.93 nM) and exhibited a 95% inhibitory concentration of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture. In addition, L-743,726 was found to be capable of inhibiting, with 95% inhibitory concentrations of ≤1.5 μM, a panel of NNRTI-resistant mutant viruses, each of which expressed a single RT amino acid substitution. Derivation of virus with notably reduced susceptibility to the inhibitor required prolonged cell culture selection and was mediated by a combination of at least two RT amino acid substitutions. Studies of L-743,726 in rats, monkeys, and a chimpanzee demonstrated the compound's potential for good oral bioavailability and pharmacokinetics in humans.