Barlow JW et al synthesized a novel dimeric 1,2,3,4-tetrahydro-naphthalenylamine and indan-1-ylamine derivatives and evaluated for mast cell-stabilizing and anti-allergic activity. Among that compound (2) exhibited potent mast cell-stabilizing activity in vitro against a variety of stimuli and also in vivo against passive cutaneous anaphylaxis. 4
Adam J et al synthesized individual stereoisomer of 3-methyl (1,2,3,4-tetrahydro-2-naphthalenyl) amino-1-indanone and evaluated for in-vitro and in-vivo mast cell stabilising activity. Stereoisomer (3) was the most active isomer in vivo, exhibiting superior activity compare to disodium cromoglycate. 21
Analgesic agent
Walsh JJ et al synthesized A novel series of amine and amide derivatives of 4-amino-3,4-dihydro-2H-naphthalen-1-one. The amine derivatives were evaluated for mast cell stabilising activity in rodent mast cell preparations against the reference compound disodium cromoglycate and found to possess significant activity in vitro. The amide compounds were evaluated in an in vivo murine model for anti-inflammatory activity. All compounds were synthesized by ring expansion of core amino-indanone (4) skeleton and then evaluated for activity. Compound (5) was found to be good anti-inflammatory agent while compound (6) showed good mast cell stabilizer against all synthesized compounds. 5
Anti convulsant agent
Masereel Bernard et al synthesized a series of aromatic sulfonamides incorporating indane moieties starting from commercially available 1 and 2-indanamine and evaluated for their activity as inhibitors of two carbonic anhydrase Isozyme, hCA I and II. Among all the new sulfonamide compounds incorporating acetamido (7), 4-chloro-benzoyl (8), Valproyl (9), tetrafluorobenzoyl (10) and pentafluorobenzoyl (11) moieties acted as potent inhibitors of the slow red blood cell Isozyme hCA I (Ks in the range of 1.6–8.5 nM), which usually has a lower affinity for such inhibitors, as compared to Isozyme II act as a very potent anti convulsant agents. 6
Ghidini Eleonora et al synthesized a series of amides of amino acids structurally related to amino acetamide and investigated for anticonvulsant activity. Among the molecules investigated, those containing a bicyclic (tetralinyl, indanyl) group linked to the amino acetamide chain (12, 13, 14) were among the most active as anticonvulsants (ED> 10, <100 mg/kg after oral administration) against tonic seizures in the mouse maximal electroshock, Bicuculline and Picrotoxin tests at doses devoid of neurotoxic activity. Altogether, these results suggest the described compounds as a class of orally available anticonvulsants. 22
Patrick Jimonet et al synthesised a novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno 1,2-e pyrazin derivatives. Among them 9-(1H-tetrazol-5-ylmethyl)-4-oxo-5,10-dihydroimidazo1,2-aindeno1,2-epyrazin-2-yl phosphoric acid (15) exhibited a strong and a selective binding affinity for the AMPA receptor and demonstrated potent antagonist activity at the ionotropic AMPA receptor. It also displayed good anticonvulsant properties against electrically-induced convulsions. 23
Dopamine β-monooxygenase inhibitory agent
Lacazio Gilles et al synthesized the four diastereoisomers of 1-fluoro-2-amino-indane and started to evaluate for Dopamine β-monooxygenase inhibitory activity which are under investigation. Among all compounds, compounds (16, 17) obtained in high enantiomer excess. 24
Anti-leukemic agent
Ugliarolo Esteban et al synthesized a series of new chiral 6-substituted purinyl and 8-aza-purinyl carbonucleosides based on indanol from the commercially available (1R, 2S)-1-amino-2-indanol and (1S, 2R)-1-amino-2-indanol and biological evaluation as anti-leukemic agents, for all the prepared compounds, is in progress. Among all synthesized compounds, compounds (18, 19) possess a very important requirement to evaluate the biological activity. 7
Anti-Parkinson agent
Bertolini G et al synthesized derivatives of cis and trans-4-phenyl-6,7-dihydroxy-2-aminotetraline and trans-1-phenyl-5, 6-dihydroxy-2-amino-indane and evaluated for dopamine receptor affinity. Among all N, N-di-n-propyl derivative (20) was more active on D2 receptors. Conformational analyses were carried out using Chem-X to generate starting amino-tetralin and amino-indane conformations to be followed by energy minimizations. Chair conformation is biologically more active. 8
Stefano Di Antonio et al synthesized trans-2-amino-5(6)-fluoro-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indene to better understand the significance of the halo substituent in the trans-1-phenyl-2-aminoindane series and evaluated for dopamine like agonistic activity. Among all, Compounds (21, 22) showed high agonistic activity. 25
Anti-Viral agents
Ugliarolo EA et al synthesized New chiral purinyl and 8-azapurinyl carbanucleoside derivatives based on indanol were synthesized from commercial available (1S, 2S)-trans-1-amino-2-indanol and (1R, 2R)-trans-1-amino-2-indanol using a linear methodology. The antiviral activity and cytotoxicity of these compounds were evaluated against herpes simplex virus type 1 (HSV-1) in Vero cells, bovine viral diarrhea virus (BVDV) in Mardin-Darby bovine kidney (MDBK) cells and hepatitis B virus (HBV) in HepG2 2.2.15 cell line. Two compounds (23 & 24) showed an inhibition of the HBsAg levels similar to reference drug lamivudine. Chloro purinyl nucleoside (23), derived from the cis-1-amino-2-indanol, was cytotoxic on MDBK cells and it could be a lead for developing anticancer agents. 9
Ayhan S et al synthesized Chemo enzymatic synthesis of 1S, 2R-1-amino-2-indanol (25), a key intermediate of HIV protease inhibitor, indinavir (26), enantiomerically pure 1S, 2R-1-amino-2-indanol is used as chiral auxiliary for asymmetric synthesis and is an important component of indinavir, a potent inhibitor of the protease of human immunodeficiency virus.26
Askin David et al synthesized orally-active HIV- I protease inhibitor L- 735,524 (26) in 71% isolated yield. Hydroxyethylene dipeptide isosteres (27) which contain the 1S, 2R-1-amino-2-hydroxy-indanamide (AHI) moiety can be potent inhibitors of HIV-1 protease. The orally active HIV protease inhibitor L-735,524 comprises the same 2(R)-aryl-4(S)-hydroxyl AHI array as found in earlier inhibitors. Synthesized compound shows highly active on HIV-1 protease enzyme and act as protease inhibitor. 27
Anti-microbial agents
Patel et al synthesized a compound having two fused heterocyclic ring benzimidazole and benztriazole which is fused with one nonheterocyclic indanone ring connected by Schiff base. Individually all this moiety are not giving good activity but fused compound having electron withdrawing and electron donating substitution on indanone moiety shows good bacteriostatic activity. Among which indanone ring fused with amino group (28) shows good microbial activity. 10
Anti-cancer agents
Bernard Masereel et al synthesized & evaluated Indanesulfonamide derivatives as Carbonic Anhydrase Inhibitors of the Tumor-Associated Isozyme CA IX. The carbonic anhydrase isozyme IX becomes an interesting pharmacological target due to its overexpression in cancer and its absence in normal tissue. Therefore, several indane sulfonamides were synthesized and tested for their inhibition both against the human CA IX and against two other biologically relevant isozymes (CA I and II). Structure-activity relationships are discussed and point out different compounds for its selectivity and activity against CA IX. CA IX model built by homology with another CA Isozyme already crystallized. Docking studies were performed to explore the binding mode of our indanesulfonamide derivatives. Among that they concluded that compound (29) more active. 11
Seralini Gilles et al developed a new comparative model in order to better understand the structure- function relationship s of the active site in human aromatase. They undertook the comparative inhibition of human and equine aromatases with new compounds. Infact, equine aromatase represents the only easy and available mammalian membrane-bound enzyme model. They identified two new indane derivatives which inhibited the human enzyme (IC50 = 3.5 µM and 5.9 µM) strongly and selectively while they were much less active on the equine one (IC50 > 10 µM). The hitherto known aromatase inhibitors, such as 4-hydroxyandro stenedione (4-OHA) and some other indane-related derivatives (30, 31) are equally efficient on both human and equine enzymes. These results could allow synthesis of a new family of compounds that are much more potent and selective aromatase inhibitors. 28
Ion channel inhibitor
Serge Beaudoin et al synthesized aryl sulfonamide indanes and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation without the risk of unwanted ventricular effects. Among all (1R, 2R) - Des-hydroxyl indane (32) has an IC50 of 0.033 µM and acts as a Kv 1.5 potent inhibitor and is selective against other cardiac ion channels, including hERG. 12
Protein kinase Inhibitor
Hong Hu et al synthesized Regio- and stereoisomeric indane analogs of balanol (-), a potent protein kinase C (PKC) inhibitor. In which the perhydroazepine of balanol was replaced by an indane nucleus. Analog (-)-(33) and its racemic regioisomer (34) were found to have highly potent PKC inhibitory activities. In addition, compound (33) displayed excellent kinase selectivity for PKC over PKA.13
Biologically active Peptide
Kotha Sambasivarao et al synthesized various benzo-annulated indane-based α-amino acid (AAA) derivatives (35-37) are reported via a 4+2 cycloaddition strategy using a sultine derivative, containing an AAA moiety, as a reactive diene component. By adopting this strategy various indane-based constrained AAA derivatives are prepared. Derivatives used in several instances to modify various biologically active Peptides. Also, indane-based AAAs are useful building blocks to design ladder-like’ parallel tapes in crystal engineering studies. 14
Photo labeling agent
Zon Jerzy et al synthesized six derivatives of 2-aminoindane-2-phosphonic acid and 1-amino benzyl phosphoric acid and evaluated as inhibitors of buckwheat phenylalanine ammonia-lyase (in-vitro) and as inhibitors of anthocyanin biosynthesis (in-vivo). (±)-2-Amino-4-bromoindane-2-phosphonic acid (38) was found to be the strongest inhibitor from investigated compounds. From result it was found that phenylalanine ammonia-lyase inhibitors useful in the enzyme structure studies in photo labeling experiments. 15
Amino peptidase inhibitor
Albert Defoin et al synthesized racemic homologues of 1-aminoindanone (39) and 3-amino-2-tetralone (40) evaluated for their ability to selectively inhibit the membrane-bound, zinc-dependent amino peptidase-N/CD13. Some of these novel non-peptidic compounds are potent, competitive inhibitors of the mammalian enzyme, with Ki values in the low micromolar range in spite of their minimal size (MW <200 Da). Moreover, they show an interesting selectivity profile against representative members of the amino peptidase family, that is leucine amino peptidase, Aeromonas proteolytica amino peptidase and the amino peptidase activity of leukotriene A4 hydrolase. The amino-benzosuberone derivative (41) is the most promising compound in terms of potency, stability and selectivity. 16
Thrombin inhibitor
Matin Pass et al synthesized a series of trans fused lactams containing the indane nucleus. Compound (42) has much enhanced plasma stability compared with its lactone counterpart and shows appreciable in vitro anticoagulant activity. An inhibitor of the pro-coagulant serine protease thrombin has potential benefit in a variety of thrombotic disorders. 17
Amino-Indane as Chiral ligand with various Pharmacological activities
Davies w et al synthesized chiral Indane derived Bis (oxazolines) in a highly regio- and diastereo-selective manner in a Ritter-type reaction. Chiral 2, 2'-bis (oxazoline) alkanes (43, 44) and 2-oxazolines have recently been used as ligands in a wide range of transition-metal catalyzed processes. As part of the synthesis of the orally active HIV Protease inhibitor, Indinavir and developed a highly efficient synthesis of the key amino indanol which proceed via oxazoline. 18
Katsumura Shigeo et al synthesized
new chiral auxiliaries, 7-alkyl substituted cis-1-amino-2-indanol derivatives,
these bulky cis-aminoindanol derivatives are very effective as chiral auxiliaries or ligand and
nitrogen sources in the asymmetric 6
-azaelectrocyclization. 7-methyl and 7-isopropyl
substituted cis-1amino-2-indanol derivatives (45, 46), which proved to
be very effective as chiral auxiliaries and nitrogen
sources. 29
Reglier Marius et al synthesized enantiomerically pure (1S, 2R)-epoxy indane (47) and cis-(1R, 2S)-2-amino-1-indanol (48) via highly enantioselective lipase catalyzed Trans esterification of racemic trans-2-bromo- 1-indanol. Enantiomerically pure amino-indanol has recently been described as a highly efficient chiral ligand in titanium catalyzed asymmetric Diels Alder reactions as well as a component of the inhibitor of a key enzyme in the human immunodeficiency virus (HIV). Moreover, it observed that 2-amino-l-indanol as a metabolite of dopamine-β-hydroxylase (DBH), a copper-containing monooxygenase which catalyses the transformation of dopamine into noradrenaline. 30
Tachykinin mimetic
Williams HM et al synthesized and designed of conformation ally constrained, nonpeptide templates (l, l, and 6-trisubstituted indanes) which allow the incorporation of two adjacent amino acid side chains, plus a third binding group in an orientation similar to that found in alpha-helices. Six racemic and two homo chiral were synthesized and evaluated in tachykinin receptor binding assays as molecular probes for the binding conformation of the endogenous peptides. Compounds (49, 50) found to bind with micro molar affinity to the NK1, and/or NK3 tachykinin receptor. While compound (51) selectively bind with NK3 receptor.19
Psychotropic agent
Coppola M et al summarized chemistry, clinical, pharmacological and toxicological information about 5-iodo-2-aminoindane (5-IAI), the new potential drug of abuse. In 2011, compound 5-IAI (52), a psychoactive derivative of 2-aminoindane was identified in recreational products sold in the United Kingdom.
5-IAI is a rigid analogue of p-Iodo amphetamine producing 3, 4-methylenedioxymethamphetamine (MDMA) like effects. Some evidence has shown that MDAI (53) and MMAI (54) are potent and selective serotonin releasing compounds determining a low neurotoxicity if compared with that by amphetamines. 20