- Synthesis and asymmetric resolution of a dopaminergic compound: 2-amino-5-methoxyindane
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The racemic synthesis and subsequent resolution of 2-amino-5-methoxyindane enantiomers were achieved starting from 5-bromoindan-2-ol in six steps with 38% total yield. The first step involved the substitution of the Br atom by using NaOMe in the presence of CuI to afford 5-methoxyindan-2-ol. The OH group of 5-methoxyindan-2-ol was converted into its mesylate ester, which was converted into the corresponding azide by reaction with sodium azide. The Pd-C-catalyzed hydrogenation of the azide functional group in the presence of CHCl3, followed by neutralization of the amine hydrochloride salt with NaOH, furnished the rac-2-amino-5-methoxyindane. Next, rac-2-amino-5-methoxyindane was converted into its diastereomeric amide derivatives by reaction with (R)-mandeloyl chloride. The diastereomeric amide mixture was separated by recrystallization to give the (R,S)- and (R,R)-diastereomers. The absolute configuration of the (R,S)-isomer was determined by X-ray crystallography. The hydrolysis of these diastereomers gave (R)- and (S)-2-amino-5-methoxyindane with high enantiopurity.
- Akbaba, Yusuf,G?ksu, Süleyman,?ahin, Ertan,Kili?, Hamdullah,Se?en, Hasan
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Read Online
- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 00953; 00955
(2018/11/22)
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- Synthesis method of 2-aminoindane derivative and product of 2-aminoindane derivative
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The invention provides a synthesis method of a 2-aminoindane derivative. According to the method, 5,6disubstituted 1-indanone is used as a staring raw material; bromination reaction is firstly performed; then, Gabriel reaction is performed; next, hydrazine hydrate is added; hydrolysis reaction is performed, and meanwhile, hydrazone is generated; finally, strong alkali is added into a high-boiling-point solvent to perform heating hydrolysis; the target product of the 2-aminoindane derivative is prepared. The invention also provides the 2-aminoindane derivative prepared by the synthesis method. Compared with the synthesis method of the 2-aminoindane derivative in the prior art, the synthesis method provided by the invention has the advantages that the reaction raw materials are cheap; the reaction condition is mild; the reaction steps are simple; the operation is easy; the yield of the obtained product is higher; the synthesis method is suitable for industrial production. Therefore good application prospects and market potentials are realized.
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Paragraph 0075
(2017/02/24)
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- SUBSTITUTED FLUOROETHYL UREAS AS ALPHA 2 ADRENERGIC AGENTS
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Therapeutic compounds, and methods, compositions, and medicaments related thereto are disclosed herein.
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Page/Page column 26
(2008/12/04)
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- Design and synthesis of indane-ureido-thioisobutyric acids: A novel class of PPARα agonists
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A series of aminoindane derivatives were synthesized and shown to be potent PPARα agonists. The compounds were obtained as racemates in 12 steps, and tested for PPARα activation and PPARα mediated induction of the HD gene. SAR was developed by variation to the core structure as shown within. Oral bioavailability was demonstrated in a Sprague-Dawley rat, while efficacy to reduce plasma triglycerides and plasma glucose was demonstrated in db/db mice.
- Matthews, Jay M.,Chen, Xiaoli,Cryan, Ellen,Hlasta, Dennis J.,Rybczynski, Philip J.,Strauss, Kim,Tang, Yuting,Xu, June Z.,Yang, Maria,Zhou, Lubing,Demarest, Keith T.
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p. 6773 - 6778
(2008/09/17)
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- SUBSTITUTED TETRALINS AND INDANES AND THEIR USE
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This invention features tetralin and indane compounds, compositions containing them, and methods of using them as PPAR alpha modulators to treat or inhibit the progression of, for example, diabetes.
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- SUBSTITUTED TETRALINS AND INDANES
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The invention features tetralin and indane compounds, compositions containing them, and methods of using them as PPAR alpha modulators to treat or inhibit the progression of, for example, dyslipidemia.
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- Dopamine D3 receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-Dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans
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5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D3 receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure- activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D3 antagonists. Thus, combinations of various alkyl groups were generally inactive at the D3 receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D3 binding affinity, the D2 affinity is also enhanced, resulting in a less than 4-fold preference for the D3 receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D3 antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH3·Me2S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et3SiH to give the desired product 3 in good overall yield of (～65%) from the indanone 5c.
- Haadsma-Svensson,Cleek,Dinh,Duncan,Haber,Huff,Lajiness,Nichols,Smith,Svensson,Zaya,Carlsson,Lin
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p. 4716 - 4732
(2007/10/03)
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- PREVENTIVES OR REMEDIES FOR MYOCARDITIS, DILATED CARDIOMYOPATHY AND CARDIAC INSUFFICIENCY CONTAINING NF-KAPPA B INHIBITORS AS THE ACTIVE INGREDIENT
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The present invention provides a preventive or therapeutic agents for myocarditis, dilated cardiomyopathy and heart failure comprising NF-κB inhibitors as active ingredients.
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- NF-γ(k)B INHIBITORS CONTAINING INDAN DERIVATIVES AS THE ACTIVE INGREDIENT
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An inhibitor of NF-κB comprising as an active ingredient an indan derivative represented by the general formula (I) or a salt thereof.
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- Hydropyridine derivatives
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Hydropyridine derivatives of the formula STR1 in which R1 represents carboxy, lower alkoxycarbonyl, carbamoyl, N-lower alkylcarbamoyl or N,N-di-lower alkylcarbamoyl, R2 represents hydrogen, an optionally etherified or acylated hydroxy group or an optionally acylated amino group, and R3 represents a radical of the formula R-- (Ia), R--alk1 -- (Ib) or R'=alk2 -- (Ic) in which R represents a benzocycloalkenyl radical having a total of from 8 to 12 ring carbon atoms which is bonded via a saturated carbon atom and which is unsubstituted or is mono- or poly-substituted in the benzo moiety by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, lower alkyl and/or by trifluoromethyl, and/or subsituted in the α-position by lower alkyl, and R' represents a benzocycloalkylidene radical having a total of from 8 to 12 ring carbon atoms which is unsubstituted or is mono- or poly-substituted in the benzo moiety by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, lower alkyl and/or by trifluoromethyl, and alk1 represents lower alkylene or lower alkylidene and alk2 represents lower alkyl-ω-ylidene, wherein the dotted line is intended to show that there may be a single bond or especially a double bond, and 3-aminopropionic acid compounds of the formula R3 --NH--CH2 CH2 --R1 (IVc) in which R1 and R3 have the meanings given above, and their pharmaceutically acceptable salts, have nootropic properties and can be used as nootropic active ingredients in medicaments. They are manufactured by methods known per se.
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