- Multi-purpose diazabicyclo compound, preparation method and application thereof in synthetic drugs
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The invention provides a multi-purpose diazabicyclo compound, a preparation method and an application thereof in synthesis of drugs, and belongs to the field of organic synthesis. The invention provides the multi-purpose diazabicyclo compound, the structural formula of which is as shown in formula 1: in the formula, R is any one of 2-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl or 2, 4-dinitrobenzenesulfonyl. According to the multipurpose diazabicyclo compound disclosed by the invention, two nitrogen atoms respectively have two different protecting groups, and the removing methods of the two protecting groups are different, so that the other protecting group is not influenced in the process of removing one protecting group, and therefore, the multipurpose diazabicyclo compound can be used for removing the other protecting group. The diazabicyclo compound provided by the invention is a multipurpose intermediate which can be applied to synthesis of various drugs.
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Paragraph 0052-0058
(2021/11/27)
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- Pyruvate kinase activators for use in therapy
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Described herein are methods for using compounds that activate pyruvate kinase.
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- NOVEL SUBSTITUTED DIAZABICYCLO DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel substituted diazabicyclo derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions
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- Substituted diazabicycloakane derivatives
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Compounds of formula (I) Z-Ar1—Ar2??(I) wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from an unsubstituted or substituted 5-membered heteroaryl ring; an unsubstituted or substituted 6-membered heteroaryl ring; 3,4-(methylenedioxy)phenyl; and phenyl substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.
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Page/Page column 18
(2010/02/11)
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- Substituted diazabicycloalkane derivatives
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Compounds of formula (I) [in-line-formulae]Z-Ar1—Ar2??(I) [/in-line-formulae] wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.
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Page/Page column 26
(2010/02/11)
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- Novel amides useful for treating pain
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The present invention relates to compounds of formula (I) that useful in treating pain.
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Page/Page column 15
(2010/02/10)
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- Novel amides useful for treating pain
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The present invention relates to compounds of formula (I-VII) or a pharmaceutically acceptable salt or prodrug thereof, in which A, L, R6, R7 and R8 are defined herein. The present invention also relates to methods of trating pain using these compounds and pharmaceutical compositions including these compounds.
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Page/Page column 17
(2010/02/11)
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- 3,8-Diazabicyclo[3.2.1]octanes and their use in the treatment of cardiac arrhythmias
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There is provided compounds of formula (I), wherein R1, R2 and Ra to Rb have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and v
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- Tandem cyclisation and [2,3]-Stevens rearrangement to 2-substituted pyrrolidines
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Reaction of N-methylallylamine with diethyl meso-2,5-dibromoadipate in DMF at ambient temperature in the presence of potassium carbonate led directly to the two diastereomers of diethyl 2-allyl-N-methylpyrrolidine-2,5-dicarboxylate. The reaction proceeds via a [2,3]-sigmatropic Stevens rearrangement, which occurred spontaneously under the reaction conditions. This gave a higher yield under milder conditions than the traditional Stevens reaction of diethyl N-allylpyrrolidine-2,5-dicarboxylate with iodomethane. The sequence was a key step in the synthesis of a series of analogues of the alkaloid stemofoline.
- Smith, Stephen C,Bentley, Philip D
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p. 899 - 902
(2007/10/03)
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- N-benzenesulfonyl l-proline compounds as bradykinin antagonists
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This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof wherein X1 and X2 are halo; R1 and R2 are independently hydrogen or C1-4 alkyl; R3 and R4 are each hydrogen or halo; and R5 is (a) —C3-9 diazacycloalkyl optionally substituted with C5-11 azabicycloalkyl; (b) —C3-9 azacycloalkyl-NH—(C5-11 azabicycloalkyl optionally substituted with C1-4 alkyl); (c) —NH—C1-3 alkyl-C(O)—C5-11 diazabicycloalkyl; (d) —NH—C1-3 alkyl-C(O)—NH—C5-11 azabicycloalkyl, the C5-11 azabicycloalkyl being optionally substituted with C1-4 alkyl; (e) —C3-9 azacycloalkyl optionally substituted with C3-9 azacycloalkyl; or (f) —NH—C1-5 alkyl-NH—C(O)—C4-9 cycloalkyl-NH2. These compounds are useful for the treatment of medical conditions mediated by bradykinin such as inflammation, allergic rhinitis, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.
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- N-benzenesulfonyl L-proline compounds as bradykinin antagonists
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This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof wherein X1 and X2 are halo; R1 andR2 are independently hydrogen or C1-4 alkyl; R3 and R4 are each hydrogen or halo; andR5 is(a) -C3-9 diazacycloalkyl optionally substituted with C5-11 azabicycloalkyl;(b) -C3-9 azacycloalkyl-NH-(C5-11 azabicycloalkyl optionally substituted with C1-4 alkyl);(c) -NH-C1-3 alkyl-C(O)-C5-11 diazabicycloalkyl;(d) -NH-C1-3 alkyl-C(O)-NH-C5-11 azabicycloalkyl, the C5-11 azabicycloalkyl being optionally substituted with C1-4 alkyl;(e) -C3-9 azacycloalkyl optionally substituted with C3-9 azacycloalkyl; or(f) -NH-C1-5 alkyl-NH-C(O)-C4-9 cycloalkyl-NH2. These compounds are useful for the treatment of medical conditions mediated by bradykinin such as inflammation, allergic rhinitis, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.
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- Mono- and disubstituted-3,8-diazabicyclo[3.2.1]octane derivatives as analgesics structurally related to epibatidine: Synthesis, activity, and modeling
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A series of 3,8-diazabicyclo[3.2.1]octanes substituted either at the 3 position compounds 1) or at the 8 position (compounds 2) by a chlorinated heteroaryl ring were synthesized, as potential analogues of the potent natural analgesic epibatidine. When tested in the hot plate assay, the majority of the compounds showed significant effects, the most interesting being the 3-(6-chloro-3-pyridazinyl)-3,8-diazabicyclo[3.2.1]octane (la). At a subcutaneous dose of 1 mg/kg, 1a induced a significant increase in the pain threshold, its action lasting for about 45 min. 1a also demonstrated good protection at a dose of 5 mg/kg in the mouse abdominal constriction test, while at 20 mg/kg it completely prevented the constrictions in the animals. Administration of naloxone (1 mg/kg ip) did not antagonize its antinociception while mecamylamine (2 mg/kg ip) did, thus suggesting the involvement of the nicotinic system in its action. Binding studies confirmed high affinity for the αβ2 nAChR subtype (K(i) = 4.1±0.21 nM). nAChR functional activity studies on three different cell lines showed that 1a was devoid of any activity at the neuromuscular junction. Finally, due to the analogy in their pharmacological profile with that of epibatidine, compounds were compared from a structural and conformational point of view through theoretical calculations and high-field 1H NMR spectroscopy. Results indicate that all of them present one conformation similar to that of epibatidine.
- Barlocco, Daniela,Cignarella, Giorgio,Tondi, Donatella,Vianello, Paola,Villa, Stefania,Bartolini, Alessandro,Ghelardini, Carla,Galeotti, Nicoletta,Anderson, David J.,Kuntzweiler, Theresa A.,Colombo, Diego,Toma, Lucio
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p. 674 - 681
(2007/10/03)
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- Synthesis and μ-opioid receptor affinity of a new series of nitro substituted 3,8-diazabicyclo[3.2.1]octane derivatives
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A new series of analogues (1c-j; 2c-i) of the previously reported analgesic 3,8-diazabicyclo[3.2.1]octanes (1a,b; 2a,b) was synthesized and tested for their affinity towards μ-opioid receptors. Modifications were introduced either at the cinnamyl or the acyl side chains. The majority of the new compounds, with the exception of 1c,j and 2c, showed K(i) values better or comparable with those of the models.
- Barlocco,Cignarella,Vianello,Villa,Pinna,Fadda,Fratta
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p. 557 - 562
(2007/10/03)
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- Synthesis and opioid receptor affinity of bivalent ligands derived from 3,8-diazabicyclo(3.2.1)octanes
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A new series of bivalent ligands (2a-d), derived from the previously reported analgesic 3-cinnamyl-8-propionyl-3,8-diazabicyclo(3.2.1)octane (1a), has been synthesized and tested in vitro for their affinity towards opioid receptors and in vivo for their analgesic potency. None of the new compounds showed either appreciable affinity for opioid receptors or analgesic activity comparable to that of the model 1a.
- Barlocco,Fadda,Fratta
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p. 387 - 396
(2007/10/02)
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