- Trans-Selective and Switchable Arene Hydrogenation of Phenol Derivatives
-
A trans-selective arene hydrogenation of abundant phenol derivatives catalyzed by a commercially available heterogeneous palladium catalyst is reported. The described method tolerates a variety of functional groups and provides access to a broad scope of trans-configurated cyclohexanols as potential building blocks for life sciences and beyond in a one-step procedure. The transformation is strategically important because arene hydrogenation preferentially delivers the opposite cis-isomers. The diastereoselectivity of the phenol hydrogenation can be switched to the cis-isomers by employing rhodium-based catalysts. Moreover, a protocol for the chemoselective hydrogenation of phenols to cyclohexanones was developed.
- Bergander, Klaus,Glorius, Frank,Heusler, Arne,Wollenburg, Marco
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p. 11365 - 11370
(2020/11/24)
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- Dihydropyrimidine compound and uses of dihydropyrimidine compound in drugs
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The present invention relates to a dihydropyrimidine compound and uses of the dihydropyrimidine compound as drugs, particularly as drugs for treatment and prevention of hepatitis B, particularly to acompound represented by a general formula (I) or (Ia) or an enantiomer, a diastereomer, a tautomer, a hydrate, a solvate or a pharmaceutically acceptable salt thereof, wherein each variable is definedin the specification. The invention further relates to uses of the compound represented by a general formula (I) or (Ia) or the enantiomer, the diastereomer, the tautomer, the hydrate, the solvate orthe pharmaceutically acceptable salt thereof as drugs, especially as drugs for treatment and prevention of hepatitis B. The formulas (I) and (Ia) are defined in the specification.
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-
Paragraph 0764; 0765; 0766; 0767
(2019/01/16)
-
- DIHYDROPYRIMIDINE COMPOUNDS AND USES THEREOF IN MEDICINE
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Provided herein are a dihydropyrimidine compound and a pharmaceutical application thereof, especially the application used for treating and preventing HBV diseases. Specifically, provided herein is a compound having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein the variables of the formulas are as defined in the specification. Also provided herein is use of the compound having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof as a medicine, especially for treating and preventing HBV diseases.
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Paragraph 00289
(2019/01/17)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
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Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
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Page/Page column 50-51
(2018/03/09)
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- FACTOR XIA-INHIBITING PYRIDOBENZAZEPINE AND PYRIDOBENZAZOCINE DERIVATIVES
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The invention relates to substituted pyridobenzazepine and pyridobenzazocine derivatives and to processes for preparation thereof, and also to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders.
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Paragraph 0772-0774
(2017/10/10)
-
- Discovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma
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Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead molecule with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound 16 (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclinical efficacy and safety profile, the compound was advanced into clinical trials.
- Yamada, Ken,Brousseau, Margaret,Honma, Wataru,Iimura, Akiko,Imase, Hidetomo,Iwaki, Yuki,Kawanami, Toshio,Lasala, Daniel,Liang, Guiqing,Mitani, Hironobu,Nonomura, Kazuhiko,Ohmori, Osamu,Pan, Meihui,Rigel, Dean F.,Umemura, Ichiro,Yasoshima, Kayo,Zhu, Guoming,Mogi, Muneto
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p. 8466 - 8481
(2017/11/03)
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- A nitric oxide-dexamethasone and preparation method and use thereof
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The invention relates to nitric oxide donor type hexadecadrol as well as a preparation method and application thereof. The nitric oxide donor type hexadecadrol as a compound is obtained by enabling nitrous acid ester to be connected with hexadecadrol through ethyl cyclohexanecarboxylate; the in-vitro antiinflammatory activity of the nitric oxide donor type hexadecadrol is better than that of the hexadecadrol; besides, the nitric oxide donor type hexadecadrol can restrain the growth of methicillin-resistant staphylococcus aureus (MRSA) in vitro, restrain the formation of MRSA biomembrane, and lead to the death of bacteria in the MRSA biomembrane. In addition, the compound can notably increase the survival rate of mice in MRSA sepsis lethal models, reduces the inflammation pathology damage of the mice in sub-sepsis models, decreases the constant value number of bacteria, and has notable advantages in the respect of preventing and treating MRSA sepsis.
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Paragraph 0045; 0046
(2017/01/17)
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- SULFIDE ALKYL COMPOUNDS FOR HBV TREATMENT
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The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.
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Paragraph 0354
(2016/06/28)
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- PYRROLO PYRIMIDINE DERIVATIVE
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The compound represented by general formula (I) has strong Axl inhibition activity by means of a pyridone ring structure being introduced into a pyrrolo pyrimidine skeleton, and so the result can serve as a treatment agent for Axl-related diseases, for example cancers such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glial tumors, renal disease, immune system disorders, and cardiovascular disease.
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Paragraph 0360
(2016/09/26)
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- NOVEL CARBOXYLIC ACID COMPOUNDS USEFUL FOR INHIBITING MICROSOMAL PROSTAGLANDIN E2 SYNTHASE-1
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The present invention provides compounds of Formula 1, or a pharmaceutically acceptable salts, thereof, where R, X, A, E, and G are as described herein, methods of preparing the compounds, and use of the compounds to treat pain and/or inflammation.
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Page/Page column 31
(2016/05/19)
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- PIPERAZINE DERIVATIVES AS HIV PROTEASE INHIBITORS
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The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.
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Page/Page column 46
(2015/10/05)
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- BICYCLIC HETEROARYL DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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Bicyclic heteroaryl derivatives of Formula 1, and pharmaceutically acceptable salts, isomers, hydrates and solvates thereof can selectively and effectively inhibit DGAT1, and thus can be useful as medicines for effectively treating dangerous diseases such as obesity, type 2 diabetes, abnormal lipidemia, metabolic syndrome (syndrome X) and the like, which are caused by DGAT1, with no adverse side effects.
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Page/Page column 22
(2013/11/05)
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- THIADIAZOLE AND OXADIAZOLE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
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The invention relates to compounds of the formula (I) either (i) in the state of a base or an acid addition salt, or (ii) in the state of an acid or a base addition salt, as well as to a method for preparing same and to the therapeutic applications thereof.
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Paragraph 0281
(2013/03/26)
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- BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS
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Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
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Page/Page column 88-89
(2011/02/24)
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- DIURETICS
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A compound having the structure (I) wherein R is selected from the group consisting of 1) and 2), or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.
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Page/Page column 17-18
(2011/05/11)
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- Compounds Which Modulate The CB2 Receptor
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Compounds of formula (I) are disclosed. Compounds according to the and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.
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Page/Page column 72-73
(2010/02/17)
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- The structure - Activity relationship of the antimalarial ozonide arterolane (OZ277)
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The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro.Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.
- Dong, Yuxiang,Wittlin, Sergio,Sriraghavan, Kamaraj,Chollet, Jacques,Charman, Susan A.,Charman, William N.,Scheurer, Christian,Urwyler, Heinrich,Tomas, Josefina Santo,Snyder, Christopher,Creek, Darren J.,Morizzi, Julia,Koltun, Maria,Matile, Hugues,Wang, Xiaofang,Padmanilayam, Maniyan,Tang, Yuanqing,Dorn, Arnulf,Brun, Reto,Vennerstrom, Jonathan L.
-
experimental part
p. 481 - 491
(2010/05/02)
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- CYCLICALLY SUBSTITUTED 3,5-DICYANO-2-THIOPYRIDINES AND USE THEREOF
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The present application relates to novel 4-cycloalkyl- and 4-heterocycloalkyl-3,5-dicyano-2-thio-pyridine derivatives, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prevention of hypertension and other cardiovascular disorders.
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Page/Page column 18
(2010/02/17)
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- ARYLCYCLOHEXYLETHERS OF DIHYDROTETRAAZABENZOAZULENES
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The present invention is concerned with arylcyclohexylethers of dihydro-tetraazabenzoazulenes, i.e. arylcyclohexylethers of 5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein, their manufacture, and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.
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Page/Page column 29
(2010/06/16)
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- A simple and highly effective method for hydrogenation of arenes by [Rh(COD)Cl]2
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Hydrogenation of arenes, including chiral BINOLs and the lignin model compounds, has been achieved efficiently by using the simple complex [Rh(COD)Cl]2 as catalyst precursor.
- Wang, Da-Wei,Lu, Sheng-Mei,Zhou, Yong-Gui
-
supporting information; experimental part
p. 1282 - 1285
(2009/09/06)
-
- Alkoxyalkyl Spirocyclic Tetramic Acids and Tetronic Acids
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The invention relates to novel alkoxyalkyl spirocyclic tetramic and tetronic acids of the formula (I), in which A, B, D, Q1, Q2, Q3, Q4, G, W, X, Y and Z are as defined above, to a plurality of processes and intermediates for their preparation and to their use as pesticides and/or herbicides and/or microbicides, and also to selective herbicidal compositions comprising, firstly, the alkoxyalkyl spirocyclic tetramic and tetronic acids and, secondly, at least one crop plant compatibility-improving compound.
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Page/Page column 55
(2009/09/07)
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- ORGANIC COMPOUNDS
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The present invention provides a compound of formula (I): wherein the variants R1, R2, R3, R4, R5, R6, R7 are as defined herein, and wherein said compound is an inhibitor of CETP, and thus can be employed for the treatment of a disorder or disease mediated by CETP or responsive to the inhibition of CETP.
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Page/Page column 71
(2009/05/28)
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- Efficient synthesis of a new pipecolic acid analogue with a bicyclic structure
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This report describes the synthesis of 2-azabicyclo[2.2.2]octane-1-carboxylic acid, a constrained pipecolic acid analogue. The route gives a very good total yield starting from cheap and readily available compounds and uses very easy reactions.
- Casabona, Diego,Cativiela, Carlos
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p. 10000 - 10004
(2007/10/03)
-
- New high affinity H3 receptor agonists without a basic side chain
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In this study, we replaced the basic amine function of the known histamine H3 receptor agonists imbutamine or immepip with non-basic alcohol or hydrocarbon moieties. All compounds in this study show a moderate to high affinity for the cloned human H3 receptor and, unexpectedly, almost all of them act as potent agonists. Moreover, in the alcohol series, we consistently observed an increased selectivity for the human H3 receptor over the human H4 receptor, but none of the compounds in this series possess increased affinity and functional activity compared to their alkylamine congeners. In this new series of compounds VUF5657, 5-(1H-imidazol-4-yl)-pentan-1-ol, is the most potent histamine H3 receptor agonist (pKi = 8.0 and pEC50 = 8.1) with a 320-fold selectivity at the human H3 receptor over the human H 4 receptor.
- Kitbunnadaj, Ruengwit,Hoffmann, Marcel,Fratantoni, Silvina A.,Bongers, Gerold,Bakker, Remko A.,Wieland, Kerstin,El Jilali, Ahmed,De Esch, Iwan J. P.,Menge, Wiro M. P. B.,Timmerman, Henk,Leurs, Rob
-
p. 6309 - 6323
(2007/10/03)
-
- Monic acid derivatives
-
Compounds of formula (I): wherein, is a divalent or a trivalent, 5-membered heterocyclic group having a 6-? electron system, and containing from 1 to 4 heteroatoms, each selected from oxygen, nitrogen and sulphur;, R1 is a substituted C3 7 cycloalkyl group attached to a carbon or nitrogen of and where appropriate, R2 is a group attached to a carbon or nitrogen of and, when present, is selected from optionally substituted C1 20 alkyl, optionally substituted C3 7 cycloalkyl, optionally substituted C2 8 alkenyl, aryl, aralkyl, heterocyclyl and hydrogen;, and where the trisubstituted carbon-carbon double bond preferably has the E- configuration;, have anti-bacterial activity.
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-
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- 4-hydroxy-4-(substituted alkenyl)cyclohexanecarboxylic acids
-
The present invention relates to compounds which are 4-hydroxy-4-alkenylcyclohexanecarboxylic acid derivatives possessing leukotriene antagonist activity. The compounds are useful in the treatment of allergic diseases, particularly in the treatment of human asthma. They are prepared by the reaction of an appropriate oxaspiro compound with a mercaptoalkanoic acid derivative.
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-
- General Syntheses of 6- and 7-Carbomethoxy-trans-1-heteradecalins and 6- and 7-Carbomethoxy-trans-2-heteradecalins
-
Two routes to all of the title compounds in the oxa and aza series have been studied.The most general path, involving a cyclohexene oxide intermediate, was not successful becauase of difficulty in separating regioisomers.Allylation of 4-carbomethoxycyclohexanone (11) followed by reduction produced the required trans-disubstituted allyl alcohols, which were converted to all of the desired 6-carbomethoxy-trans-1-heteradecalins.The allyl ketones were subjected to a homologation-side chain contraction sequence to produce the 6-carbomethoxy-trans-2-heteradecalins.Allylation of 3-carbomethoxycyclohexanone (12) was not regioselective, but all four product isomers were characterized.The desired 5-carbomethoxy-2-allylcyclohexanone isomers (27 and 28) were converted to the 7-carbomethoxy-trans-decalins by similar series of reactions
- Hirsch, Jerry A.,Truc, Vu Chi
-
p. 2218 - 2227
(2007/10/02)
-
- Xanthocyclines: 5-oxaanthracyclines (7,8,9,10-tetrahydrobenzoxanthen-12-one)
-
The anthracycline antibiotics daunorubicin and adriamycin are potent antitumor agents.It has recently been suggested that 5-oxaanthracycline analogs of these compounds might show reduced cardiotoxicity, a property that limits the clinical use of the anthracyclines.In this paper we describe the condensation-cyclization reactions of 2-methylchromone-3-carboxylate with cyclohexanones, a reaction that leads ultimately to the xanthocycline skeleton.
- Charlton, James L.,Sayeed, Vilayat A.,Lypka, Gerald N.
-
p. 1996 - 2001
(2007/10/02)
-
- Benzospiran derivatives
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This invention relates to novel benzospiran derivatives embraced by the formula SPC1 Wherein the sum of A and B is at least the integer 2; A is selected from the group consisting of --(CH2)n -- wherein n is 1 through 5 and --(Cn H2n --2 XY)-- wherein X is selected from the group consisting of hydroxy, acetoxy, amino and acetamido and Y is hydrogen, and X when taken together with Y is selected from the group consisting of =O and =CR3 R4 wherein R3 and R4 are selected from the group consisting of hydrogen and lower alkyl of 1 through 3 carbon atoms; B is absent or --(CH2)n -- wherein n is 1 through 3; R1 is selected from the group consisting of hydrogen and lower alkyl of 1 through 3 carbon atoms; R2 is selected from the group consisting of hydrogen, lower alkyl of 1 through 3 carbon atoms, EQU1 WHEREIN N IS 2 THROUGH 5 AND Ar is phenyl having zero through three substituents selected from the group consisting of lower alkyl of 1 through 3 carbon atoms, lower alkoxy of 1 through 3 carbon atoms, bromine, chlorine and fluorine; R1 and R2 taken together with --N is a saturated heterocyclic amino radical selected from the group consisting of unsubstituted and substituted pyrrolidino, piperidino, and hexamethylenimino; Z is selected from the group consisting of hydrogen, lower alkyl of 1 through 3 carbon atoms, lower alkoxy of 1 through 3 carbon atoms, nitro, amino, monoalkylamino of 1 through 3 carbon atoms, acylamido of 1 through 4 carbon atoms, bromine, chlorine and fluorine; and a pharmacologically acceptable acid addition salt thereof. It also relates to intermediates and processes for the preparation of the aforesaid novel compounds (1) and novel derivatives thereof. The administration to humans and animals of the novel compounds (1) depresses their central nervous systems and lowers their blood pressures.
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