- Successive Pd-Catalyzed Decarboxylative Cross-Couplings for the Modular Synthesis of Non-Symmetric Di-Aryl-Substituted Thiophenes
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Oligothiophenes are important organic molecules in a number of burgeoning industries as semi-conducting materials due to their extensive π-conjugation and charge transport properties. Typically, non-symmetric, di-aryl-substituted thiophenes are prepared by the successive formation of Grignards, organotin, and/or boronic acid intermediates that can be subsequently employed in cross-coupling reactions. While reliable, these approaches present synthetic difficulties due to the reactivity of organo-metallic/pseudo-metallic species, and produce considerable amounts of waste due to necessary pre-functionalization. We have developed a decarboxylative cross-coupling route as an effective strategy for the modular and less wasteful synthesis of a wide range of non-symmetric, di-arylthiophenes. This method uses a thiophene ester building block for successive decarboxylative palladium-catalyzed couplings that allows for the efficient synthesis and evaluation of the opto-electronic properties of a library of candidate semi-conductors with functional groups that could be challenging to access using previous routes.
- Douglas, Liam Z.,Forgione, Pat,Liu, Jiang Tian,Messina, Cynthia
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supporting information
(2020/08/17)
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- HETEROARYL-SUBSTITUTED TRIAZOLES AS APJ RECEPTOR AGONISTS
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Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.
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Paragraph 0671-0672
(2018/06/12)
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- TBK/IKK INHIBITOR COMPOUNDS AND USES THEREOF
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The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.
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Paragraph 1247; 1248
(2017/01/23)
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- PYRROLOPYRROLONE DERIVATIVES AND THEIR USE AS BET INHIBITORS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Page/Page column 92; 94; 95
(2015/06/08)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 57
(2008/12/08)
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- Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
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Methods of treating one or more conditions associated with p38 kinase activity are disclosed comprising administering to a patient in need thereof at least one compound having the formula (I): 1or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein R3 is hydrogen, methyl, perfluoromethyl, methoxy, halogen, cyano, or NH2, preferably methyl, and X, R1 through R6, and Z are as described in the specification. Advantageously the groups —ZR4R5 taken together comprise an —NH-substituted aryl.
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- Pyrroloazepine derivatives
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A method for treating a circulatory disease or condition in a mammal, which entails administering to the mammal an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt thereof: wherein the ring P represented by ?is a pyrrole ring having the following structure: wherein R1represents C1-C8alkyl, C3-C8cycloalkyl, C4-C8cycloalkyl-alkyl, C6-C14aryl or C7-C22aralkyl, which are optionally substituted; and R2represents H or C1-C8alkyl, which is optionally substituted; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2is not present and Z1represents H, but, when the bond is absent, Z1and Z2are both H; Z1represents H and Z2represents a group OR3, in which R3represents H, C1-C8alkyl, or C7-C22aralkyl, which are optionally substituted; Z1and Z2both represent groups SR4, in which R4represents C1-C8alkyl or C7-C22aralkyl, which are optionally substituted; or Z1and Z2are combined together to represent O, a group NOR5, in which R5represents H, or C1-C8alkyl or C2-C3alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C═ or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C═O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E1and E2is H or C1-C8alkyl; and D represents an aromatic hydrocarbon or an aromatic heterocyclic ring. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is therapeutically useful in the treatment of circulatory diseases and/or conditions related thereto.
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- Synthesis and serotonin 2 (5-HT2) receptor antagonist activity of 5- aminoalkyl-substituted pyrrolo [3,2-c]azepines and related compounds
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A series of 5-aminoalkylpyrrolo[3,2,c]azepine derivatives was synthesized and their serotonin 2 (5-HT2) receptor antagonist and antiplatelet aggregation activities were evaluated. 5-HT2 receptor antagonist activity was largely determined by the nature of the substituent at the 8-position as well as the aminoalkyl group at the 5-position of the pyrrolo[3,2-c]azepine ring. Compound 18a, 5-[3-[4-(4-(4- fluorophenyl)piperazin-1-yl]propyl]-8-hydroxy-1-methyl-1,4,5,6,7,8- hexahydropyrrolo[3,2-c]azepin-4-one, was recognized as having potent 5-HT2 receptor antagonist activity with weak α1 adrenoceptor blocking activity and no significant D2 receptor binding affinity, while the corresponding isomeric pyrrolo[3,4-c]azepine derivative (22) displayed only weak 5-HT2 receptor antagonist activity. After racemic 18a was resolved directly via diastereomeric salt formation, each enantiomer was evaluated precisely. The 5-HT2 receptor antagonist activity of 18a was found to reside primarily in (-)-18a (which was about 14-fold more potent than (+)-18a in isolated guinea pig arteries). Consequently, (S)-(-)-18a (SUN C5174)displayed the overall best profile with potent 5-HT2 receptor antagonist activity (pA2 = 8.98 ± 0.06) and high selectivity versus other receptors. SUN C5174 showed a marked inhibitory effect on the platelet aggregation induced by serotonin in combination with collagen and adenosine diphosphate (ADP) in canine or human platelet-rich plasma (IC50 = 6.5 to 16 nM). Moreover, this compound significantly inhibited the mortality rate in mouse acute pulmonary thromboembolitic death induced by collagen and serotonin at oral doses of 0.3 mg/kg or higher. SUN C5174 is currently undergoing clinical evaluation.
- Mizuno, Akira,Ogata, Atsuto,Kamei, Tomoe,Shibata, Makoto,Shimamoto, Tetsuo,Hayashi, Yasuhiro,Nakanishi, Kyoko,Takiguchi, Chikako,Oka, Naomi,Inomata, Norio
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p. 623 - 635
(2007/10/03)
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- Pyrroloazepine derivatives
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A pyrroloazepine compound having the following formula (I): wherein the ring P represented by STR1 is a pyrrole ring having the following structure: STR2 wherein R1 represents C1 -C8 alkyl, C3 -C8 cycloalkyl, C4 -C8 cycloalkyl-alkyl, C6 -C14 aryl or C7 -C22 aralkyl, which are optionally substituted; and R2 represents H or C1 -C8 alkyl, which is optionally substituted; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2 is not present and Z1 represents H, but, when the bond is absent, Z1 and Z2 are both H; Z1 represents H and Z2 represents a group OR3, in which R3 represents H, C1 -C8 alkyl, or C7 -C22 aralkyl, which are optionally substituted; Z1 and Z2 both represent groups SR4, in which R4 represents C1 -C8 alkyl or C7 -C22 aralkyl, which are optionally substituted; or Z1 and Z2 are combined together to represent O, a group NOR5, in which R5 represents H, or C1 -C8 alkyl or C2 -C3 alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C= or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C=O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E1 and E2 is H or C1 -C8 alkyl; and D represents an aromatic hydrocarbon or an aromatic heterocyclic ring. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is therapeutically useful in the treatment of circulatory diseases and/or conditions related thereto.
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- Process for preparing 1-substituted pyrrole-3-carboxylic acid derivatives
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A simple and industrially viable process for preparing a 1-substituted pyrrole-3-carboxylic acid derivative of formula (I) is provided. The process comprises reacting a compound of formula (II), a compound of formula (III), and an acid anhydride according
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- Process for preparing 1-substituted pyrrole-3-carboxylic acid derivatives
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A simple and industrially viable process for preparing a 1-substituted pyrrole-3-carboxylic acid derivative of formula (I) is provided. The process comprises reacting a compound of formula (II), a compound of formula (III), and an acid anhydride according
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