- 3,6-DIAMINO-PYRIDAZIN-3-YL DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USES AS PRO-APOPTOTIC AGENTS
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Compounds of formula (I) wherein Het1, Het2, R1, R2 and R3 are as defined in the description. Medicaments.
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Page/Page column 145
(2021/02/05)
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- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY
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This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol APLNR). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.
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Page/Page column 324; 325
(2020/05/15)
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- Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA)
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SMA is an inherited disease that leads to loss of motor function and ambulation and a reduced life expectancy. We have been working to develop orally administrated, systemically distributed small molecules to increase levels of functional SMN protein. Compound 2 was the first SMN2 splicing modifier tested in clinical trials in healthy volunteers and SMA patients. It was safe and well tolerated and increased SMN protein levels up to 2-fold in patients. Nevertheless, its development was stopped as a precautionary measure because retinal toxicity was observed in cynomolgus monkeys after chronic daily oral dosing (39 weeks) at exposures in excess of those investigated in patients. Herein, we describe the discovery of 1 (risdiplam, RG7916, RO7034067) that focused on thorough pharmacology, DMPK and safety characterization and optimization. This compound is undergoing pivotal clinical trials and is a promising medicine for the treatment of patients in all ages and stages with SMA.
- Ratni, Hasane,Ebeling, Martin,Baird, John,Bendels, Stefanie,Bylund, Johan,Chen, Karen S.,Denk, Nora,Feng, Zhihua,Green, Luke,Guerard, Melanie,Jablonski, Philippe,Jacobsen, Bjoern,Khwaja, Omar,Kletzl, Heidemarie,Ko, Chien-Ping,Kustermann, Stefan,Marquet, Anne,Metzger, Friedrich,Mueller, Barbara,Naryshkin, Nikolai A.,Paushkin, Sergey V.,Pinard, Emmanuel,Poirier, Agnès,Reutlinger, Michael,Weetall, Marla,Zeller, Andreas,Zhao, Xin,Mueller, Lutz
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p. 6501 - 6517
(2018/08/17)
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- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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Provided herein are novel substituted bicyclic aza-heterocycle sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Paragraph 0362; 0363
(2017/04/04)
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- COMPOUNDS FOR TREATING AMYOTROPHIC LATERAL SCLEROSIS
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The present invention provides compounds of formula (I) (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof for use in the treatment, prevention and/or delay of progression of amyotrophic lateral sclerosis (ALS). Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.
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Page/Page column 33
(2017/06/01)
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- COMPOSITIONS FOR TREATING SPINAL MUSCULAR ATROPHY
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The present invention provides pharmaceutical compositions comprising a compound of formula (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the pharmaceutical compositions comprising a compound of formula (I) and their use as medicaments.
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Page/Page column 55
(2017/05/28)
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- SUBSTITUTED IMIDAZO[1,2-b]PYRIDAZINES, SUBSTITUTED IMIDAZO[1,5-b]PYRIDAZINES, RELATED COMPOUNDS, AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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The invention provides substituted imidazo[1,2-b]pyridazine compounds, substituted imidazo[1,5-b]pyridazine compounds, related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,2-b]pyridazine compounds described herein include substituted imidazo[1,2-b]pyridazine-3-carboxamide compounds and variants thereof.
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Paragraph 00254; 00322
(2017/12/14)
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- ROR NUCLEAR RECEPTOR MODULATORS
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The invention provides compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological conditions.
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Page/Page column 68
(2016/12/26)
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- IMIDAZOPYRIDAZINES USEFUL AS INHIBITORS OF THE PAR-2 SIGNALING PATHWAY
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The present invention relates to compounds useful as inhibitors of the PAR-2 signaling pathway. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, dis
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Paragraph 00190
(2015/04/15)
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- COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY
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The present invention provides compounds of formula (I) wherein A, R1, R2 and R3 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.
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Page/Page column 33
(2015/12/23)
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- TRIAZOLO COMPOUNDS
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The present invention relates to compounds of formula (I) and its use for the treatment of neurological disorders.
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Page/Page column 48
(2014/05/24)
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- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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Provided herein are novel substituted bicyclic aza-heterocycle sirtuin- modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin- modulating compound in combination with another therapeutic agent.
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Page/Page column 105
(2013/05/09)
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- COMPOUNDS AND METHODS FOR ANTIVIRAL TREATMENT
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Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections
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Paragraph 0675-0677
(2013/10/22)
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- IMIDAZO [1, 2 - B] PYRIDAZINE - BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND USES THEREOF
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Imidazo[1,2-b]pyridazine-based compounds of the formula (I): are disclosed, wherein R1, R2 and R3 are defined herein. Compositions comprising the compounds and methods of their use to treat, manage and/or prevent diseases and disorders mediated by mediated by adaptor associated kinase 1 activity are also disclosed.
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Page/Page column 71
(2013/09/26)
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- 6-CYCLOAMINO-3-(1H-PYRROLO[2,3-b]PYRIDIN-4-YL)IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
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The invention relates to 6-cycloamino-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazine derivatives corresponding to the general formula (I) in which R2 represents an aryl group optionally substituted with one or more halogen atoms or C1-6-alkyl, C1-6-alkyloxy, C1-6-alkylthio, C1-6-fluoroalkyl, C1-6-fluoroalkyloxy and —CN groups or R2 represents a group chosen from C1-6-alkyl, C1-6-fluoroalkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-6-alkyl groups; A represents a C1-7-alkylene group; B represents a C1-7-alkylene group; L represents either a nitrogen atom optionally substituted with an Rc or Rd group, or a carbon atom substituted with an Re1 group and an Rd group or two Re2 groups; the carbon atoms of A and of B being optionally substituted with one or more Rf groups, which may be identical to or different from one another. Preparation process and therapeutic use.
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Page/Page column 6
(2012/01/15)
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- IMIDAZO [1,2-B] PYRIDAZINE AND IMIDAZO [4,5-B] PYRIDINE DERIVATIVES AS JAK INHIBITORS
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New imidazo[1,2-b]pyridazine and imidazo[4,5-b]pyridine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).
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Page/Page column 54-55
(2012/06/15)
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- Imidazo[1,2-b]pyridazine derivatives as JAK inhibitors
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New imidazo[1,2-b]pyridazine derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).
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Page/Page column 22
(2012/06/18)
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- SUBSTITUTED AMINOIMIDAZOPYRIDAZINES
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The present invention relates to substituted aminoimidazopyridazine compounds of general formula (I) : in which A, R1, R2, R3 and R4 are as defined in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comp
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Page/Page column 79
(2013/02/28)
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- 2-ALKYL-6-CYCLOAMINO-3-(PYRIDIN-4-YL)IMIDAZO[1,2-B]-PYRIDAZINE DERIVATIVES, PREPARATION THEREOF, AND THERAPEUTIC APPLICATION THEREOF
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The invention relates to 2-alkyl-6-cycloamino-3-(pyridin-4-yl)imidazo[1,2-b]pyridazine derivatives of the general formula (I) where: R2 is a C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-4-alkyl, C1-4-alkyloxy-C-M-alkyl, C3-7-cycloalkyloxy-C1-4-alkyl>C3-7-cycloalkyl-C1-4-alkyloxy-C1-4-alkyl, hydroxy-C1-6-alkyl, C1-4-fluoroalkyl group; R3 is a hydrogen atom or a substituent selected from halogen atoms and the C1-3 alkyl, —NR4R5, hydroxyl or C1-4 alkyloxy groups; A is a C1-7-alkylene group optionally substituted by one or two Ra groups; B is a C1-7-alkylene group optionally substituted by one or two Rb groups; L is either a nitrogen atom optionally substituted by an Rc or Rd group or a carbon atom substituted by an Re1 group and an Rd group or by two Re2 groups; Rd is a group selected from a hydrogen atom or a C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-6-alkyl, C1-6-alkylthio-C1-6-alkyl, C1-6-alkyloxy-C1-6-alkyl, C1-6-fluoroalkyl, hydroxy-C1-6-alkyl group; Rf is a C1-6-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-6-alkyl, C1-6-alkyloxy-C1-6-alkyl, C3-7-cycloalkyloxy-C1-4-alkyl, C3-7-cycloalkyl-C1-4-alkyloxy-C1-4-alkyl, hydroxy-C1-6-allyl, C1-6-fluoroalkyl or benzyl group. The invention also relates to a method for preparing same and to the therapeutic application thereof.
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Page/Page column 17
(2012/01/13)
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- IMIDAZOPYRIDAZINE DERIVATIVES ACTING AS OREXIN ANTAGONISTS
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This invention, relates to imidazopyridazine substituted piperidine derivatives (I) and their use as orexin antagonists.
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Page/Page column 15
(2010/06/17)
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- NOVEL COMPOUNDS
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This invention relates to imidazopyridazine substituted piperidine derivatives and their use as pharmaceuticals.
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Page/Page column 8
(2010/11/03)
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- AZETIDINE DERIVATIVES
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Compounds of formula (I) are inhibitors of fatty acid amide hydrolase, (FAAH), and which are useful in the treatment of diseases or medical conditions which benefit from inhibition of FAAH activity, such as anxiety, depression pain, inflammation, and eating, sleep, neurodegenerative and movement disorders: Formula (I) Wherein Ar1 is optionally substituted phenyl or optionally substituted monocyclic heteroaryl having 5 or 6 ring atoms; Ar2 is optionally substituted phenyl, optionally substituted monocyclic heteroaryl having 5 or 6 ring atoms or optionally substituted fused bicyclic heteroaryl having 5 or 6 ring atoms in each fused ring; and Ar3 is a divalent radical selected from the group consisting of optionally substituted phenylene and optionally substituted monocyclic heteroarylene radicals having 5 or 6 ring atoms.
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Page/Page column 52; 53
(2009/10/22)
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- IMIDAZO[1,2-B]PYRIDAZINE AND PYRAZOLO[1,5-A]PYRIMIDINE DERIVATIVES AND THEIR USE AS PROTEIN KINASE INHIBITORS
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The present invention provides protein kinase inhibitors comprising imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine compounds of the following structure (I) and (II), or a stereoisomer, prodrug or pharmaceutically acceptable salt thereof, wherein R, R1, R2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer and other Pim kinase-associated conditions are also disclosed.
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Page/Page column 65
(2008/12/05)
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- ALZHEIMER'S DISEASE IMAGING AGENTS
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This invention provides compounds and methods of imaging amyloid deposits using radiolabeled compounds. This invention also provides a method of inhibiting the aggregation of amyloid proteins to form amyloid plaques or deposits, a method of determining a therapeutic compound's ability to inhibit aggregation of amyloid protein, and a method of delivering a therapeutic agent to amyloid deposits.
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Page/Page column 26; 37
(2008/06/13)
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- Fused heterocyclic compounds useful as kinase modulators
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Compounds having the formula (1), and enantiomers, and diastereomers, pharmaceutically-acceptable salts, thereof, are usefuil as kinase modulators, including MK2 modulation, wherein one of E and F is a nitrogen atom and the other of E and F is a carbon atom, Z is N or CR3, and R1, R2, R3, X and Y are as defined herein.
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Page/Page column 46
(2010/11/26)
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- Bisaryl-sulfonamides
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Compounds, compositions and methods are provided that are useful in the treatment or prevention of a condition or disorder mediated by PPARγ or PPARδ. In particular, the compounds of the invention modulate the function of PPARγ or PPARδ. The subject methods are particularly useful in the treatment and/or prevention of diabetes, obesity, hypercholesterolemia, rheumatoid arthritis and atherosclerosis.
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Page/Page column 75
(2008/06/13)
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- Imidazopyridazines. I Some 3-Alkoxy-6-halogeno-2-phenyl(and 4'-substituted phenyl)inidazopyridazines and 3-Methoxy-2,6-diphenylimidazopyridazine
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A series of 3-alkoxy-6-halogeno-2-phenyl(and 4'-substituted phenyl)imidazopyridazines (1) and 3-methoxy-2,6-diphenylimidazopyridazine have been prepared from the relevant pyridazin-3-amines and arylglyoxals, followed by O-alkylation of the c
- Barlin, Gordon B.
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p. 1803 - 1809
(2007/10/02)
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