- Cross-Coupling of Alkyl Redox-Active Esters with Benzophenone Imines: Tandem Photoredox and Copper Catalysis
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Alkyl amines are an important class of organic compounds in medicinal and materials chemistry. Until now very have been very few methods for the synthesis of alkyl amines by metal-catalyzed cross-coupling of alkyl electrophiles with nitrogen nucleophiles. Described here is an approach to employ tandem photoredox and copper catalysis to enable the cross-coupling of alkyl N-hydroxyphthalimide esters, readily derived from alkyl carboxylic acids, with benzophenone-derived imines. Hydrolysis of the coupling products furnish alkylated primary amines. Primary, secondary, and tertiary alkyl groups can be transferred, and the coupling tolerates a diverse set of functional groups. The method allows rapid functionalization of natural products and drugs, and can be used to expedite syntheses of pharmaceuticals from readily available chemical feedstocks.
- Mao, Runze,Balon, Jonathan,Hu, Xile
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p. 9501 - 9504
(2018/07/29)
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- Pyrazolo[3,4-b]pyridine compounds, and their use as a PDE4 inhibitors
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The invention provides a compound of formula (I) or a salt thereof: wherein R2 is H, C1-3alkyl, n-butyl, C1-2fluoroalkyl, cyclopropyl, cyclobutyl, (cyclopropyl)methyl-, —CN, or —CH2OH; R3 is inter alia optionally substituted C4-7cycloalkyl or an optionally substituted heterocyclic group (aa), (bb) or (cc); Ra is H, methyl or ethyl; Rb is H or methyl; R4 is H, methyl, ethyl, n-propyl, —C(O)-Me, or —C(O)—C1fluoroalkyl; and R5 is: —C(O)—(CH2)n—Ar, —C(O)-Het, —C(O)—C1-6alkyl, —C(O)—C1 fluoroalkyl, —C(O)—(CH2)2—C(O)—NR15bNR15b, —C(O)—CH2—C(O)—NR15bNR15b, —C(O)—NR15b—(CH2)m1—Ar, —C(O)—NR15b—Het, —C(O)—NR15b—C1-6alkyl, —C(O)—NR5aR5b, —S(O)2—(CH2)m2—Ar, —S(O)2-Het, —S(O)2—C1-6alkyl, or —CH2—Ar; or R4 and R5 taken together are —(CH2)p1—, —(CH2)2—X5—(CH2)2—, —C(O)—(CH2)p2—, —C(O)—N(R15)—(CH2)p3—; or NR4R5 is of sub-formula (y), (y1), (y2) or (y3). The invention provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as COPD and the like.
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Page/Page column 76
(2009/05/28)
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- PYRIDO-PYRIDIMIDINE DERIVATIVES USEFUL AS ANTIINFLAMMATORY AGENTS
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Provided are novel pyrido-pyrimidine derivatives, having the structure of Formula (I): which can be used as anti-inflammatory agents. Also provided are pharmaceutical compositions comprising one or more pyrido-pyrimidine derivatives, as well as methods of
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Page/Page column 42
(2008/06/13)
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- PYRAZOLO[3,4-B]PYRIDINE COMPOUNDS, AND THEIR USE AS PDE4 INHIBITORS
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The invention provides a compound of formula (I) or a salt thereof: wherein R2 is H, C1-3alkyl, n butyl, C1-2fluoroalkyl, cyclopropyl, cyclobutyl, (cyclopropyl)methyl , CN, or CH2OH; R3 is inter alia optionally substituted C4-7cycloalkyl or an optionally substituted heterocyclic group (aa), (bb) or (cc); Ra is H, methyl or ethyl; Rb is H or methyl; R4 is H, methyl, ethyl, n propyl, C(O) Me, or C(O) C1fluoroalkyl; and R5 is: C(O) (CH2)n Ar, C(O) Het, C(O) C1 6alkyl, C(O) C1fluoroalkyl, C(O) (CH2)2 C(O) NR15bNR15b, C(O) CH2 C(O) NR15bNR15b, C(O) NR15b (CH2)m1 Ar, C(O) NR15b Het, C(O) NR15b C1-6 alkyl, C(O) NR5aR5b, S(O)2 (CH2)m2-Ar, S(O)2 Het, S(O)2-C1-6alkyl, or CH2 Ar; or R4 and R5 taken together are-(CH2)p1-, (CH2)2 X5 (CH2)2 , C(O) (CH2)p2 ,-C(O)-N(R15) (CH2)p3 ; or NR4R5 is of sub-formula (y), (y1), (y2) or (y3). The invention also provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis, psoriasis or atopic dermatitis.
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Page/Page column 154
(2010/11/26)
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- PROCESS FOR PRODUCTION OF 4-AMINOTETRAHYDROPYRANS AND SALTS THEREOF WITH ACIDS, INTERMEDIATES FOR THE PROCESS, AND PROCESS FOR PRODUCTION THEREOF
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The present invention relates to a process for preparing 4-aminotetrahydropyran compound and an acid salt thereof represented by the formula (2): wherein R represents a hydrogen atom or a hydrocarbon group, which comprises subjecting a 4-hydrazinotetrahydropyran compound or an acid salt thereof represented by the formula (1) : wherein R has the same meaning as defined above, to decomposition reaction in the presence of at least one compound selected from Raney nickel, noble metal catalyst and metal oxide, and a synthetic intermediate thereof and a process for preparing the same.
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Page/Page column 8
(2008/06/13)
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- PYRROLOPYRIDINE DERIVATIVE AND USE THEREOF
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A novel pyrrolopyridine derivative which is a compound represented by the formula ???wherein Ring A represents an optionally substituted pyridine ring; X represents an electron-attracting group; Y represents an optionally substituted divalent C1-6 chain hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; and R2 and R3 each independently represents hydrogen, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R2 and R3 may form an optionally substituted ring in cooperation with the adjacent nitrogen atom, or a salt of the compound. The pyrrolopyridine derivative has vanilloid receptor agonist activity and is useful as medicines such as a preventive/therapeutic agent and analgesic for overactive bladder.
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Page/Page column 40
(2008/06/13)
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- PYRAZOLO[3,4-B]PYRIDINE COMPOUNDS, AND THEIR USE AS PHOSPHODIESTERASE INHIBITORS
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The invention relates to a compound of formula (I) or a salt thereof: wherein:R1 is C1-4alkyl, C1-3fluoroalkyl, -CH2CH2OH or -CH2CH2CO2C1-2alkyl;R2 is a hydrogen atom (H), methyl or C1fluoroalkyl;R3 is optionally substituted C3-8cycloalkyl or optionally substituted mono-unsaturated-C5-7cycloalkenyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); in which n1 and n2 independently are 1 or 2; and in which Y is O, S, SO2, or NR10; or R3 is a bicyclic group (dd) or (ee): ; and wherein X is NR4R5 or OR5a. The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.
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- Novel guanidinobenzamides
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Compounds of formula IA and IB are new where the variables R1 through R10 have the values set forth herein. Such compounds have use in treating diseases such as obesity and type II diabetes, and may be provided as pharmaceutical form
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