cas 366-77-8, 3-(4-Fluorobenzoyl)propionic acid

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Role of CYP3A in bromperidol metabolism in rat in vitro and in vivo
1. The aim was to identify whether CYP3A metabolizes bromperidol (BP), an antipsychotic drug, to form 4-fluorobenzoyl-propionic acid (FBPA) in hepatic microsomes from 8-week-old male Sprague-Dawley rats and to investigate whether an inhibitor or an inducer of CYP3A affects BP pharmacokinetics in rat. 2. In an in vitro study, only troleandomycin showed marked inhibition of FBPA formation among several specific CYP isozyme inhibitors studied including troleandomycin, diethyldithiocarbamate, furafylline and quinine. Anti-rat CYP3A2 serum inhibited FBPA formation by 80%, whereas other anti-rat CYP sera (1A1, 1A2, 2B1, 2C11, 2E1) only slightly inhibited it. 3. In a pharmacokinetic study, BP half-life was prolonged to 137% of the average control value by 7-day treatment with erythromycin, a CYP3A inhibitor, and shortened to 58% of the control by 2-day treatment with dexamethasone, a CYP3A inducer. BP clearance was reduced to 68% of the control by erythromycin and was increased to 145% of control by dexamethasone. 4. These results suggested that BP biotransformation is catalysed mainly by CYP3A to form FBPA in rat and that the modification of this enzyme activity would affect the pharmacokinetics of BP.
Watanabe,Tateishi,Tanaka,Kumai,Kobayashi
p. 839 - 846
(1999)
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Design and Synthesis of Butenolide-based Novel Benzyl Pyrrolones: Their TNF-α based Molecular Docking with in vivo and in vitro Anti-inflammatory Activity
A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF-α target. Among all the docked molecules, compound 3f showed best glide score of -6.89. All the synthesized compounds were evaluated for in vivo anti-inflammatory activity by carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory activity were further tested for their in vitro TNF α expression. Compounds 3b and 2b were found to show significant inhibition of 76.22% and 71.47%, respectively after 5 h in comparison with standard drug indomethacin, which showed 80.98% inhibition of inflammation. Compounds 3b and 2b also suppressed TNF α level by 65.03% and 60.90% as compared indomethacin, which showed 68.84% of inhibition. Compound 3b showed significant analgesic activity of 60.04%, and its activity was comparable with indomethacin (64.04%). Compounds 3b and 2b were also tested for their effect on protein expression of COX-2 and NF-κB in the liver tissues. Compounds 3b and 2b were further evaluated for their gastric risk and lipid peroxidation action and showed superior GI safety along with reduction of LPO as compared to indomethacin. Hepatotoxicity study showed that these two compounds did not cause any damage to liver.
Ali, Yakub,Alam, Mohammad Sarwar,Hamid, Hinna,Husain, Asif,Shafi, Syed,Dhulap, Abhijeet,Hussain, Firasat,Bano, Sameena,Kharbanda, Chetna,Nazreen, Syed,Haider, Saqlain
p. 619 - 625
(2015)
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Method for synthesizing 4-(4-fluorobenzoyl) butyric acid and analogues thereof in continuous flow microreactor
The invention relates to a method for synthesizing 4-(4-fluorobenzoyl) butyric acid and analogues thereof in a continuous flow microreactor, which comprises the following steps: (1) uniformly mixing a compound 1 and a compound 2 to obtain a homogeneous phase solution A; (2) uniformly mixing aluminum trichloride, a compound 1 and an organic solvent to obtain a homogeneous phase solution B; (3) diluting concentrated hydrochloric acid with water to prepare a solution C; and (4) transferring the homogeneous phase solution A and the homogeneous phase solution B into a first micro-reaction module for a Friedel-Crafts acylation reaction, after the reaction is finished, transferring the obtained reaction solution and the solution C into a second micro-reaction module for quenching reaction, and then performing liquid separation, washing and vacuum concentration to obtain a target compound 3; wherein the specific synthesis route is as follows. By adopting the method disclosed by the invention, the target product can be continuously and rapidly synthesized, aluminum trichloride is not needed for treatment, the reaction condition is mild, the reaction time is short, and the yield is high and reaches 90% or above.
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Paragraph 0047-0052

(2021/05/12)

Practical Synthesis of (3a R, 9b R)-8-Fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1 H-benzo[e]indole: An Advanced Intermediate to Access the RORγt Inverse Agonist BMT-362265
A practical and scalable route to (3aR, 9bR)-8-fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole 10, an advanced intermediate en route to the synthesis of the RORγt inverse agonist, BMT-362265, is described starting from fluorobenzene. The synthesis involved the screening of multiple synthetic routes for their feasibility and scalability. We also demonstrate the utility of an annulating reagent, (R)-N-(2-chloroethyl)-2-methylpropane-2-sulfinamide, for the diastereoselective synthesis of tricyclic pyrrolidine intermediates 24 and 36 on a multigram scale.
Karmakar, Ananta,Nimje, Roshan Y.,Silamkoti, Arundutt,Pitchai, Manivel,Basha, Mushkin,Singarayer, Christuraj,Ramasamy, Duraisamy,Babu, G. T. Venkatesh,Samikannu, Ramesh,Subramaniam, Srinath,Anjanappa, Prakash,Vetrichelvan, Muthalagu,Kumar, Hemantha,Dikundwar, Amol G.,Gupta, Anuradha,Gupta, Arun Kumar,Rampulla, Richard,Dhar, T. G. Murali,Mathur, Arvind
p. 1001 - 1014
(2021/04/12)

In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold
Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site. Subsequently, all the derivatives were primarily deduced for their antidiabetic potential by OGTT. The compounds that showed significant antidiabetic activity in OGT Test and also exhibited high dock scores were assessed further by in vitro PPAR transactivation assay to assure analogy between in vivo and in vitro studies. The antidiabetic activity of these active compounds was then evaluated on STZ induced diabetic model in vivo. The most active compounds were scrutinized for its effect on PPAR-γ gene expression and hepatotoxic effect. Finally, it was recapitulated that these derivatives can provide a new prospect towards the development of antidiabetic agents with fewer side effects.
Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Ali, Yakub,Nazreen, Syed,Dhulap, Abhijeet,Alam, Perwez,Pasha
(2020/11/27)

A class of histone acetylase p300 inhibitors, and application thereof
The invention discloses a class of histone acetylase p300 inhibitors, and application thereof, and belongs to the technical field of medicinal chemistry. The invention discloses a compound representedby a formula (I), or a stereochemical isomer, a solvate or a pharmaceutically acceptable salt thereof. According to the invention, the compound can effectively inhibit the activity of histone acetylase p300 and can effectively inhibit the proliferation activity of various tumor cells; the compound is combined with a CDK4/6 inhibitor to play a synergistic role in inhibiting proliferation of tumorcells; and the compound has good application prospects in preparation of histone acetylase inhibitors, preparation of drugs for preventing and/or treating cancers, metabolic diseases, neurological diseases or inflammations, and combination of drugs.
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Paragraph 0345-0346; 1118-1122

(2020/06/17)

Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
supporting information
p. 2707 - 2713
(2020/03/30)

Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
(2020/04/07)

Synthesis of Enantiopure γ-Lactones via a RuPHOX-Ru Catalyzed Asymmetric Hydrogenation of γ-Keto Acids
A RuPHOX?Ru catalyzed asymmetric hydrogenation of γ-keto acids has been developed, affording the corresponding enantiopure γ-lactones in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 10000 S/C) under the indicated reaction conditions and the resulting products can be transformed to several enantiopure building blocks, biologically active compounds and enantiopure drugs. (Figure presented.).
Li, Jing,Ma, Yujie,Lu, Yufei,Liu, Yangang,Liu, Delong,Zhang, Wanbin
supporting information
p. 1146 - 1153
(2019/01/30)

Synthesis of Novel Pterocarpen Analogues via [3?+?2] Coupling-Elimination Cascade of α,α-Dicyanoolefins with Quinone Monoimines
By employing triethylamine as a catalyst, [3?+?2] coupling-elimination cascade of α,α-dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.
Chen, Hui,Zhao, Sihan,Cheng, Shaobing,Dai, Xingjie,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
p. 1672 - 1683
(2019/04/08)

Cooperative iodine and photoredox catalysis for direct oxidative lactonization of carboxylic acids
A new method for the formation of γ- and δ-lactones from carboxylic acids through direct conversion of benzylic C-H to C-O bonds is described. The reaction is conveniently induced by visible light and relies on a mild cooperative catalysis by the combination of molecular iodine and an organic dye.
Duhamel, Thomas,Mu?iz, Kilian
supporting information
p. 933 - 936
(2019/01/23)

Visible-light-induced oxidation/[3 + 2] cycloaddition/oxidative aromatization to construct benzo[ a]carbazoles from 1,2,3,4-tetrahydronaphthalene and arylhydrazine hydrochlorides
An efficient synthesis of benzo[a]carbazoles via visible-light-induced tandem oxidation/[3 + 2] cycloaddition/oxidative aromatization reactions was reported. The benzylic C(sp3)-H of tetrahydronaphthalene was activated through visible-light photoredox catalyst with oxygen as the clean oxidant under mild reaction conditions. This protocol proceeds efficiently with broad substrate scope, and the mechanism study was performed.
Shen, Jiaxuan,Li, Nannan,Yu, Yanjiang,Ma, Chunhua
supporting information
p. 7179 - 7183
(2019/09/30)

Synthesis method of canagliflozin intermediate
The invention relates to a synthesis method of a canagliflozin intermediate. Concretely, succinyl oxide and fluorobenzene are used as starting raw materials to be prepared into the canagliflozin crucial intermediate of 2-(4-fluorophenyl)-5-[(5-halogen-2-methyl phenyl)methyl]thiophene through the steps of Friedel-Crafts acylation ring opening, thiophene ring preparation, Friedel-Crafts acylation coupling, reduction and the like. The cheap succinyl oxide is used for preparing the thiophene ring, so that the Suzuki coupling reaction and Grignard reaction are avoided; the use of heavy metal reagents of palladium and the like is avoided; the production process is simplified; the product yield and the quality are improved; the environment pollution is reduced; the production cost is reduced.
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Paragraph 0036; 0037; 0038; 0039; 0040; 0052; 0053

(2018/03/26)

Unravelling the Nucleophilicity of Butenolides for 1,6-Conjugate Addition to p-Quinone Methides: A Direct Access to Diversely Substituted Butenolide-Derived Diarylmethanes
A Lewis acid catalyzed regioselective C-C bond is constructed through β-addition of deconjugated butenolides with p-quinone methides in a 1,6-conjugate addition manner. Interestingly, Lewis acid catalyzed vinylogous Mukaiyama-Michael reaction of silyloxyfurans with p-QMs proceeds selectively through the α or γ position exclusively. The reaction is mild with broad substrate scope, thus allowing easy access to a wide range of bis-arylated α-/β-/γ-substituted butenolides.
Sharma, Brijesh M.,Shinde, Dinesh R.,Jain, Ruchi,Begari, Eeshwaraiah,Satbhaiya, Shruti,Gonnade, Rajesh G.,Kumar, Pradeep
supporting information
p. 2787 - 2791
(2018/05/17)

Divergent Access to (1,1) and (1,2)-Azidolactones from Alkenes using Hypervalent Iodine Reagents
A versatile synthesis of azidolactones through azidation and cyclization of carboxylic acids onto alkenes has been developed. Based on either photoredox or palladium catalysis, (1,1) and (1,2) azido lactones can be selectively synthesized. The choice of catalyst and benziodoxol(on)e reagent serving as azide source was essential to initiate either a radical or Lewis acid mediated process with divergent outcome. These transformations were carried out under mild conditions using a low catalyst loading and gave access to a large scope of azido lactones.
Alazet, Sébastien,Le Vaillant, Franck,Nicolai, Stefano,Courant, Thibaut,Waser, Jerome
supporting information
p. 9501 - 9504
(2017/07/22)

Efficient Hydrogenation of Biomass Oxoacids to Lactones by Using NHC–Iridium Coordination Polymers as Solid Molecular Catalysts
A series of NHC–iridium coordination polymers have proven to be robust, efficient and recyclable solid molecular catalysts toward the hydrogenation of biomass levulinic acid (LA) to γ-valerolactone. Along with quantitative yields attained at 0.01 mol % catalyst loading under 50 atm of H2, the solid molecular catalyst was readily recovered and reused for 12 runs without obvious loss of the selectivity and activity. Remarkably, up to 1.2×105 TON, an unprecedented value could be achieved in this important transformation. In addition, a number of LA homologues, analogues and derivatives were well tolerated to deliver various intriguing and functional lactones in good to excellent yields, which further confirmed the feasibility of the solid molecular catalysts.
Liu, Yaoqi,Sun, Zheming,Huang, Changyu,Tu, Tao
p. 355 - 360
(2017/02/05)

Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABAA receptor.
Partap, Sangh,Yar, Mohammad Shahar,Hassan, Md. Zaheen,Akhtar, Md. Jawaid,Siddiqui, Anees A.
(2017/10/06)

Penfluridol preparation method
The invention discloses a penfluridol preparation method. The penfluridol preparation method includes the following steps of 1), subjecting succinic anhydride and fluorobenzene to Friedel-Crafts reaction prior to acid decomposition, and collecting a compound from the formula 2) as is shown in the description; 2), putting the compound in a solvent to collect a compound in formula 3) as is shown in the description in a solvent reduced through a reducing agent; 3), putting the compound into the fluorobenzene to perform the Friedel-Crafts reaction to collect a compound in the formula 4) as is shown in the description; subjecting the compound and ethyl chloroformate to action to generate a compound in formula 5) as is shown in the description; 5), subjecting the compound and a compound shown in formula (XVII) to reaction prior to hydrolyzation to collect a compound in formula 6) as is shown in the description; 6), performing reduction with the reducing agent prior to hydrolyzing a reduction product and then collecting penfluridol (I). The penfluridol preparation method is high in yield, low in cost, moderate in reaction condition, short in circuit, proper for industrial production, low in three wastes, easy to treat and suitable for industrial production.
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Paragraph 0153; 0154; 0155; 0156; 0157; 0104-0108

(2017/02/24)

Synthesis under moderate pressure of 3-imidazo[1,2-a]pyridinylidene pyrrol-2-ones
Conversion of 3-imidazo[1,2-a]pyridinylidene furan-2-ones into their pyrrol-2-one analogues was achieved efficiently with high yields, using a solution of ammonium hydroxide under moderate pressure conditions. A NMR study showed that the compounds are mainly isolated as E isomers.
Masurier, Nicolas,Lebrun, Aurélien,Canitrot, Damien,Chezal, Jean-Michel,Moreau, Emmanuel
p. 2583 - 2586
(2016/06/01)

Cobalt-catalyzed oxidative cyclization of gem-disubstituted conjugated alkenols
Aryl gem-disubstituted conjugated alkenols underwent oxidative cyclization affording 2,5,5-trisubstituted tetrahydrofurans in reasonable yields and good diastereoselectivities using the reductive termination variation of the Mukaiyama aerobic oxidative reaction. Under oxidative termination, the same alkenols produced diols and ketonic by-products via the double hydration and beta-scission competing pathways. Furthermore, the differences in alkenol reactivity under the reductive and oxidative termination conditions were investigated.
Alves, Tania M.F.,Costa, Mateus O.,Bispo, Beatriz A.D.,Pedrosa, Fabiana L.,Ferreira, Marco A.B.
supporting information
p. 3334 - 3338
(2016/07/11)

One-pot synthesis of tetralin derivatives from 3-benzoylpropionic acids: Indium-catalyzed hydrosilylation of ketones and carboxylic acids and intramolecular cyclization
This reducing system was composed of a small amount (1 mol%) of In(OAc)3, Me2PhSiH, and I2 that effectively catalyzed the hydrosilylation of two different carbonyl groups, a ketone and a carboxylic acid found in 3-benzoylpropionic acids, followed by a subsequent intramolecular cyclization that led to the one-pot preparation of tetralin derivatives.
Sakai, Norio,Kobayashi, Taichi,Ogiwara, Yohei
supporting information
p. 1503 - 1505
(2015/11/24)

Design and synthesis of butenolide-based amide derivatives as anti-inflammatory agents
Butenolide-based eighteen new amide derivatives (1-18) have been synthesized and evaluated for anti-inflammatory activity. The compounds 9, 17 and 4 exhibited significant in vivo inhibition of 84.69, 76.52 and 76.22 % inflammation, respectively, after 5 h without causing any damage to stomach and liver in comparison with the standard drug indomethacin which showed 79.04 % inhibition. The compounds showing potent anti-inflammatory activity were further evaluated for ex vivo TNF-α suppression. Compounds 9, 17 and 4 significantly suppressed TNF-α concentration to 74.83, 71.74 and 67.11 % as compared to indomethacin which exhibited a suppression of 69.01 %. Compounds 9 and 17 were also found to suppress the expression of COX-2 and NF-κB in the paw tissue. Moreover, compound 9 showed significant analgesic activity (57.03 %) which was comparable to indomethacin (61.03 %).
Ali, Yakub,Alam, Mohammad Sarwar,Hamid, Hinna,Husain, Asif,Dhulap, Abhijeet,Bano, Sameena,Kharbanda, Chetna,Nazreen, Syed,Haider, Saqlain
p. 3775 - 3784
(2015/10/06)

Enzymatic synthesis of chiral γ-amino acids using ω-transaminase
In this study, we successfully synthesized enantiomerically pure (R)- and (S)-γ-amino acids (>99% ee) using ω-transaminase (ω-TA) through kinetic resolution and asymmetric synthesis respectively. The present study demonstrates the high potentiality of ω-TA reaction for the production of chiral γ-amino acids.
Shon, Minsu,Shanmugavel, Ramachandran,Shin, Giyoung,Mathew, Sam,Lee, Sang-Hyeup,Yun, Hyungdon
supporting information
p. 12680 - 12683
(2015/05/20)

Synthesis, antiproliferative and anti-inflammatory activities of some novel 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones
Sixteen new 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2 H)-ones (2a-p) were synthesized and tested for in vitro anticancer and in vivo anti-inflammatory activities. Eleven (2b, 2d , 2-ej and 2m-p) of the obtained compounds were screened for their antiproliferative activity towards 60 human cancer cell lines by the National Cancer Institute (USA). Compound 2f showed remarkable activity with GI50 less than 1 μM on 36 human tumor cell lines and has been referred to Biological Evaluation Committee (NCI) for advance study. Compound 2g also displayed promising antiproliferative activity against 20 different cell lines with GI50 less than 1 μM. Compounds 2k and 2n were found to have a comparable anti-inflammatory activity to that of standard drug etoricoxib in carrageenan-induced rat hind paw edema model at 5 h.
Ovais, Syed,Javed, Kalim,Yaseen, Shafiya,Bashir, Rafia,Rathore, Pooja,Yaseen, Raed,Hameed, Alhamzah D.,Samim, Mohammad
p. 352 - 358
(2013/10/01)

Design and synthesis of 2(3H)-furanone derivatives as γ-Aminobutyric acid receptor modulator
Eleven new 3-(substituted-arylidene)-5-(4-chloro-3-methyl-phenyl)-)-3H- furan-2-one were synthesized from appropriate 4-(substituted -phenyl)-4-oxo-butyric acid and isatin derivatives. Molecular docking calculations experiments were performed using EXHZ version 1.4 and Auto Dock 4.0 to identify potential g-aminobutyric acid receptor modulator among all synthesized furanones. The anticonvulsant activities of selected compounds were evaluated in mice by PTZ induced seizure method. Result indicate that all tested compounds possess anti-convulsant activity after oral administration and that the compounds 1-acetyl-3-[5-(4-bromo-phenyl) -2-oxo -furan-3-ylidene]- 1,3-dihydro-indol-2-one (C-6) and 1-acetyl-3-[5-(4-ethyl-phenyl)-2-oxo- furan-3-ylidene]-5-ethyl-1,3-dihydro-indol-2-one (C-8) possess significant anticonvulsant activity could be comparable to that of diazepam a standard.
Kumar,Ahmed,Srivastawa,Vaishali
experimental part
p. 3553 - 3556
(2012/08/14)

Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1
Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 μM in cAMP).
Rist, ystein,Grimstrup, Marie,Receveur, Jean-Marie,Frimurer, Thomas M.,Ulven, Trond,Kostenis, Evi,Hoegberg, Thomas
scheme or table
p. 1177 - 1180
(2010/06/15)

Arylalkane, arylalkene and aryl azaalkane, medicaments containing said compounds and method for the production thereof
The present invention relates to compounds of general formula [in-line-formulae]R—Z1—Z2—Z3—R1, ??(I)[/in-line-formulae] wherein R, R1 and Z1 to Z3 are defined as in claim 1, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, particularly CGRP-antagonistic properties, pharmaceutical compositions containing these compounds, their use and processes for preparing them.
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Page/Page column 65-66

(2010/11/27)

COMPOUND
There is provided a compound of Formula (I):wherein R3, R4, R5, R6, R7, R9, and R10, are independently selected from -H, -OH, hydrocarbyl groups, oxyhydrocarbyl groups, cyano (-CN), nitro (-NO2 ), and halogens; wherein ring A is optionally further substituted wherein X is a bond or a linker group wherein (A) (i) R9 is selected from alkyl and halogen groups; and (ii) R10 is selected from -OH, oxyhydrocarbyl and -OSO 2 NR1 R2 ; wherein R1 and R2 are independently selected from H and hydrocarbyl or (B) at least one of R3 , R4 , R5 , R6 and R7 is the group -C(=0)-CR11 R12 -R8 wherein R8 is a selected from (i) an alkyloxyalkyl group (ii) a nitrile group, (iii) alkylaryl group, wherein the aryl group is substituted by other than a C1-10 group (iv) alkenylaryl group wherein the aryl group is substituted (v) alkylheteroaryl group, wherein when heteroaryl group comprises only C and N in the ring, the aryl group is substituted by other than a methyl group (vi) alkenylheteroaryl group (vii) =N-O-alkyl or =N-O-H group (viii) branched alkenyl (ix) alkyl-alcohol group or alkenyl-alcohol group (x) amide or alkylamide wherein (a) the alkyl of the alkylamide is -CH 2 - or - CH 2 CH 2 -, (b) the amide is di-substituted and/or (c) the amide is substituted with at least one of alkylheterocycle group, alkenylheterocycle group, alkylheteroaryl group, alkenylheteroaryl group, heteroaryl group, alkylamine group, alkyloxyalkyl group, alkylaryl group, straight or branched alkyl group, (xi)-CHO, or together with another of R3 , R4 , R5 , R6 and R7 the enol tautomer thereof wherein R11 and R12 are independently selected from H and hydrocarbyl; or (C) at least one of R3 , R4 , R5 , R6 and R7 together with another of R3 , R4 , R5 , R6 and R7 forms a ring containing -C(=O)-; or (D) at least one of R3 , R4 , R5 , R6 and R7 is selected from alkylheterocycle group, alkenylheterocycle group, alkylheteroaryl group, alkenylheteroaryl group, and heteroaryl groups or (E) at least one of R3 , R4 , R5 , R6 and R7 is selected from -CN, -C(R13 )=N-O-alkyl group, - C(R14 )=N-O-H group, optionally substituted pyrazole, optionally substituted thiazole, optionally substituted oxazole, optionally substituted isoxazole, optionally substituted pyridine, and optionally substituted pyrimidine, or together with another of R3 , R4 , R5 , R6 and R7 forms a nitrogen containing ring; wherein R13 and R14 are independently selected from H and hydrocarbyl
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Page/Page column 148-149

(2008/06/13)

AMINO-SUBSTITUTED AZO-HETEROCYCLIC COMPOUNDS FOR TREATING INFLAMMATORY CONDITIONS
Compounds of formula (I) are CRTH2 antagonists, useful in the treatment of inflammatory, autoimmune, respiratory or allergy disease: wherein X1 is -S-, -O-, -N=N-. -NR5-, -CR5=CR6-, -CR5=N-, wherein R5 and R6 are independently hydrogen or C1-C3 alkyl; R1 is hydrogen or C1-C3 alkyl or cyclopropyl; R2 is an optionally substituted phenyl or 5- or 6-membered monocyclic heteroaryl ring; R3 is an optionally substituted carbocyclic ring of 3 to 7 ring atoms, or an optionally substituted 4-, 5- or 6-membered monocyclic heterocyclic ring; R4 is a group other than hydrogen, methyl or ethyl of formula Q-[Alk1]m-[X]n-[Alk2]p-[Z}s- wherein m, n p, and s are independently 0 or 1 ; Q is hydrogen or an optionally substituted 4-, 5- or 6-membered monocyclic heterocyclic ring; Alk1 and Alk2 are independently optionally substituted C1-C3 alkylene radicals; X is -O-, -S-, -C(=O)-, - S(=O)-, -S(=O)2-, -CH(R7)-, -N(R7)-, or, in either orientation -SO2N(R7)- or - C(=O)N(R7)-, wherein R7 is hydrogen, or R7 represents a C2-C4 bridge between the C or N atom of X to which it is attached and a carbon atom of Alk2 and Z is -CH2, - C(=O) or -S(=O)2.
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Page/Page column 16-17

(2008/06/13)

Arylsulfonyl naphthalene derivatives and uses thereof
Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, q, Ar, R1, R2 and R7 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formula I.
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Page/Page column 30

(2008/06/13)

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF
Compounds of the formula I, II or III; or pharmaceutically acceptable salts thereof, wherein m, n, q, Ar, R1, R2, R3, R4 and R5 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formulas I-III.
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Page/Page column 43-44

(2008/06/13)

Asymmetric synthesis of 2-aryl-5-oxotetrahydrofuran-2-carboxylic acids
3-Aryl-2-hydroxycyclopent-2-en-1-ones, when subjected to asymmetric oxidation, result in enantiomerically enriched 2-aryl-5-oxotetrahydrofuran-2- carboxylic acids. Electron-donating substituents in the para position of the phenyl ring increase the yield and decrease the enantioselectivity of the process. Georg Thieme Verlag Stuttgart.
Jogi, Artur,Paju, Anne,Pehk, Tonis,Kailas, Tiiu,Mueuerisepp, Aleksander-Mati,Kanger, Tonis,Lopp, Margus
p. 3031 - 3036
(2008/02/08)

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF AS 5-HT ANTAGONISTS
Compounds of the formula (I) or pharmaceutically acceptable salts thereof, wherein m, p, q, Ar, R1 and R 2 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formula (I).
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Page/Page column 26

(2008/06/13)

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF
Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein R2 is (CR3R4)n-NR5R6 and m, p, q, Ar, R1, R3, R4, R5 and R6 are as defined in the claims, which are selective antagonists of 5-HT6 and/or 5-HT2A. Also provided are compositions comprising these compounds and their use in the preparation of medicaments for treating central nervous system disease states selected from psychoses, schizophrenia, manic depressions, neurological disorders, memory disorders, attention deficit disorder, Parkinson’s disease, amyotrophic lateral scierosis, Alzheimer’s disease, food uptake disorders and Huntington’s disease.
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Page/Page column 74; 75

(2008/06/13)

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF
Compounds of the formula (I) or pharmaceutically acceptable salts thereof, wherein R2 is a group of formula (II) and m, n, p, q, r, Rl and X are as defined in the claims, which are selective agonists of 5-HT6 and 5-HT2A. Also provided are compositions comprising these compounds and methods for their use in the preparation of medicaments for treating central nervous system disease states and disorders of the gastrointestinal tract.
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Page/Page column 24

(2008/06/13)

A simple procedure for the isolation of γ-oxobenzenebutanoic acid derivatives: Application to the synthesis of fenbufen
A simple, convenient, and industrially viable process for the isolation of 4-oxobutanoic acid derivatives resulting from Friedel-Crafts acylation products of aromatic hydrocarbons with succinic anhydride is reported. The isolation procedure involves simple quenching of the reaction mixture followed by filtration of the product in good yield and with excellent purity. The generality of the procedure has been demonstrated with representative examples of aromatic hydrocarbon precursors and has also been applied to the isolation of fenbufen. The quantity of aluminum chloride used in the reaction has also been optimized to reduce the load on effluent.
Srinivas,Haricharan Raju,Acharyulu, Palle V. R.
p. 291 - 292
(2013/09/04)

Bicyclic amide derivatives and their use as muscle relaxants
Novel compounds of formula (1) together with their salts and solvates have a number of uses in medicine, in particular as central muscle relaxants.
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(2008/06/13)

Bicyclic amide derivatives and their use as muscle relaxants
Novel compounds of formula (I) STR1 wherein R1, R2, R3 and R4 are each selected from hydrogen and fluoro and at least one and not more than two is fluoro; R5 is selected from hydrogen and C1 -C4 alkyl; R6 is selected from hydrogen, C1 -C4 ally and hydroxy; or R5 and R6 together with the ring carbon form a carbonyl group; R7 is selected from hydrogen and hydroxy, R8 and R9 are each selected from hydrogen, C1 -C4 alkyl and cyclo(C3 or C4) alkyl or together with the nitrogen form a morpholino group; and X is selected from a bond, methylene and --O-- and is always a bond or --O-- when any of R5, R6 and R7 is other than hydrogen and is always a bond when R5 and R6 together with the ring carbon form a carbonyl group; and their salts and solvates have a number of uses as central muscle relaxants. In particular, treatment of conditions associated with abnormally raised skeletal muscle tone. They are of special value in the relaxation of skeletal muscle in spastic, hypertonic and hyperkinetic conditions.
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(2008/06/13)

Amide derivatives and their therapeutic use
Novel carbocyclic amides together with their salts, solvates and physiologically active derivatives which have a number of uses in medicine, in particular as central muscle relaxants, and in the treatment or prophylaxis of anxiety, inflammation, arthritis and pain.
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(2008/06/13)

Synthesis, structure, and antimalarial activity of some enantiomerically pure, cis-fused cyclopenteno-1,2,4-trioxanes
Two pairs of enantiomerically pure cis-fused cyclopenteno-1,2,4-trioxanes (7, ent-7 and 8, ent-8) are prepared. Their identities are established by dye-sensitized photo-oxygenation of ent-7 and 8 to the allylic hydroperoxides, reduction to the corresponding alcohols, and conversion to the (1S)-camphanoates, the structures of which are determined by X-ray analysis. The dynamic properties of ent-7 are investigated by NMR spectroscopy and PM3 calculations. Evidence for an easily accessible twist-boat conformation is obtained. The in vitro and in vivo antimalarial activities of 7, ent-7, 8, and ent-8 as well as those of the racemic mixtures are evaluated against Plasmodium falciparum, P. berghei, and P. yoelii. No correlation is observed between configuration and activity. Racemates and pure enantiomers have commensurate activities. The mode of action on the intraerythrocytic parasite is rationalized in terms of close docking by the twist-boat conformer of the trioxane on the surface of a molecule of heme, single-electron transfer to the O-O σ* orbital, and scission to the acetal radical which then irreversibly isomerizes to a C-centered radical, the ultimate lethal agent.
Jefford,Kohmoto,Jaggi,Timari,Rossier,Rudaz,Barbuzzi,Gerard,Burger,Kamalaprija,Mareda,Bernardinelli,Manzanares,Canfield,Fleck,Robinson,Peters
p. 647 - 662
(2007/10/02)

Compound, 8-fluoro-5-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-hydroxybutyryl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
8-Fluoro-5-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-hydroxybutyryl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]-indole; processes therefor; and process for the conversion to flutroline.
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(2008/06/13)

Cardiotonic Agents. 1. 4,5-Dihydro-6--3(2H)-pyridazinones: Novel Positive Inotropic Agents for the Treatment of Congestive Heart Failure
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Bristol, James A.,Sircar, Ila,Moos, Walter H.,Evans, Dale B.,Weishaar, Ronald E.
p. 1099 - 1101
(2007/10/02)

Synthesis and central nervous system depressant activity of some bicyclic amides
A series of aryl bicycle analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a aryl 3,4,6,7,8,8a hexahydro 2H pyrrolo[2,1 b] [1,3]oxazin 6 ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital.
Aeberli,Gogerty,Houlihan,Iorio
p. 436 - 438
(2007/10/06)