68251-76-3

Upstream product

• 861353-11-9 5-bromo-2-methyl-[1]naphthylamine 
• 1013-83-8 5-bromonaphthalene-2-carboxylic acid 
• 128104-53-0 5-Bromo-2-hydroxymethyl-naphthalene 
• 128104-54-1 5-bromo-2-naphthalenylmethyl bromide 
• 3333-20-8 1-allyl-3-methylbenzene 
• 861333-94-0 5-bromo-2-methyl-1-nitro-naphthalene 
• 412041-50-0 1,2-diethynyl-4-methylbenzene 

Downstream Products

• 63409-04-1 6-methyl-1-naphthaldehyde 
• 122349-66-0 5-bromonaphthalene-2-carbaldehyde 

Relevant academic research and scientific papers

A Visible Light and Iron-mediated Carbocationic Route to Polysubstituted 1-Halonaphthalenes by Benzannulation using Allylbenzenes and Polyhalomethanes

A wide array of polysubstituted 1-bromo and chloronaphthalenes are obtained from coupling of allylbenzenes and polyhalomethanes. The reaction is mediated by iron metal under visible light irradiation and proceeds via a Kharasch addition intermediate followed by intramolecular FeIII mediated Friedel-Crafts alkylation, with the formation of two Csp2?Csp2 bonds in the process. This method gives easy access to 1-halonaphthalenes with substituent(s) at C-5 to C-8 that are otherwise hard to synthesize. (Figure presented.).

KRAS G12D INHIBITORS

The present invention relates to compounds that inhibit KRas G12D. In particular, the present invention relates to compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor.

COMPOUNDS FOR BINDING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9)

The present disclosure relates to novel compounds, methods, and compositions capable of binding to PCSK9, thereby modulating PCSK9 proprotein convertase enzyme activity. The compounds of the disclosure include compounds Formula (I).

Potent 4-aryl- or 4-arylalkyl-substituted 3-isoxazolol GABAA antagonists: Synthesis, pharmacology, and molecular modeling

We have previously described a series of competitive GABAA antagonists derived from the low-efficacy partial agonist 5-(4-piperidyl)-3- isoxazolol (4-PIOL, 4). The 2-naphthylmethyl analogue, 4-(2-naphthylmethyl)-5- (4-piperidyl)-3-isoxazolol (5), provided affinity for the GABAA receptor site higher than that of the standard GABAA receptor antagonist, SR 95531 (3). Molecular modeling studies of these compounds exposed a cavity at the receptor recognition site capable of accommodating aromatic groups of substantial size in the 4-position in the 3-isoxazolol ring. Here we present a series of analogues of 5, with various substituents in different positions in the naphthyl ring system (6a-k), and compounds with aromatic substituents directly attached to the 4-position of the 3-isoxazolol ring (71-n). The compounds have been pharmacologically characterized using receptor-binding assays and electrophysiological whole-cell patch-clamp techniques. All of the tested compounds show affinity for the GABAA receptor site. While the 5-, 7-, and 8-bromo analogues, 6b-d, showed receptor affinities (Ki = 45, 109, and 80 nM, respectively) comparable with that of 5 (Ki = 49 nM), the 1-bromo analogue, 6a, provided the highest receptor affinity of the series (Ki = 10 nM). Introduction of a series of different substituents in the 1-position in the 2-naphthyl ring system led to compounds, 6c-k, with retained high affinity for the GABA A receptor (Ki = 16-250 nM). Introduction of a phenyl ring directly into the 4-position on the 3-isoxazolol ring gave a 41-fold increase in affinity relative to that of 4-PIOL. In whole-cell patch-clamp recordings from cultured cerebral cortical neurons, all of the tested compounds were able to inhibit the effect of the specific GABAA agonist isoguvacine, 6a showing antagonist potency (IC50 = 42 nM) markedly higher than that of 3 (IC50 = 240 nM). Molecular modeling studies, based on the compounds described, emphasized the importance of the distal ring in 5 for receptor affinity and the considerable dimensions of the proposed receptor cavity. Furthermore, the phenyl rings in 71 and in 6k were shown to represent highly favorable positions for an aromatic ring in previously unexplored receptor regions in terms of a pharmacophore model.

Regioselective haloaromatization of 1,2-bis(ethynyl)benzene via halogen acids and PtCl2. Platinum-catalyzed 6-π electrocyclization of 1,2-bis(1′-haloethenyl)benzene intermediates

Treatment of 1,2-bis(ethynyl)benzene (1) with aqueous HX (X = Br, I) in hot 3-pentanone (100-105 °C, 2 h) afforded 1,2-bis(1′-haloethenyl)benzene species 2-Br and 2-I in 98% and 95% yields, respectively. The hydrochlorination of endiyne 1 failed to proceed at elevated temperature but was implemented efficiently by PtCl2 (5 mol %) in hot 3-pentanone (100 °C, 2 h) to give 1,2-bis(1′-chloroetheny)benzene 2-Cl in 80% yield. In the presence of PtCl2 (5 mol %), these halides 2-Cl, 2-Br, and 2-I were subsequently converted to 1-halonaphthalenes 3-Cl, 3-Br, and 3-I in the mother solution via sequential 6-π electrocyclization and dehalogenation reactions. PtCl2 (5 mol %) also effected direct haloaromatization of endiyne 1 with HX (X = Cl, Br, I) and gave 1-halonaphthalenes 3-Cl, 3-Br, and 3-I in 64-71% yields. This investigation reports the scope and the regioselectivity of haloaromatization of various enediynes catalyzed by PtCl2.

HETEROCYCLIC DERIVATIVES

The invention concerns a heterocyclic derivative of the formula I, or a pharmaceutically-acceptable salt there of. The compounds of the invention are inhibitors of the enzyme 5-lipoxygenase.