- Potent, orally active corticotropin-releasing factor receptor-1 antagonists containing a tricyclic pyrrolopyridine or pyrazolopyridine core
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Two new classes of tricyclic-based corticotropin-releasing factor (CRF 1) receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based molecules 19g and
- Dyck, Brian,Grigoriadis, Dimitri E.,Gross, Raymond S.,Guo, Zhiqiang,Haddach, Mustapha,Marinkovic, Dragan,McCarthy, James R.,Moorjani, Manisha,Regan, Collin F.,Saunders, John,Schwaebe, Michael K.,Szabo, Tomas,Williams, John P.,Zhang, Xiaohu,Bozigian, Haig,Chen, Ta Rung
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Read Online
- Pd(II)-Catalyzed Enantioselective C(sp3)-H Arylation of Cyclopropanes and Cyclobutanes Guided by Tertiary Alkylamines
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Strained aminomethyl-cycloalkanes are a recurrent scaffold in medicinal chemistry due to their unique structural features that give rise to a range of biological properties. Here, we report a palladium-catalyzed enantioselective C(sp3)-H arylation of aminomethyl-cyclopropanes and -cyclobutanes with aryl boronic acids. A range of native tertiary alkylamine groups are able to direct C-H cleavage and forge carbon-aryl bonds on the strained cycloalkanes framework as single diastereomers and with excellent enantiomeric ratios. Central to the success of this strategy is the use of a simple N-acetyl amino acid ligand, which not only controls the enantioselectivity but also promotes γ-C-H activation of over other pathways. Computational analysis of the cyclopalladation step provides an understanding of how enantioselective C-H cleavage occurs and revealed distinct transition structures to our previous work on enantioselective desymmetrization of N-isobutyl tertiary alkylamines. This straightforward and operationally simple method simplifies the construction of functionalized aminomethyl-strained cycloalkanes, which we believe will find widespread use in academic and industrial settings relating to the synthesis of biologically active small molecules.
- Gaunt, Matthew J.,Miró, Javier,Reeve, Luke A.,Rodrigalvarez, Jesus
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supporting information
p. 3939 - 3948
(2022/03/08)
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- SUBSTITUTED BICYCLIC DIHYDROPYRIMIDINONES AND THEIR USE AS INHIBITORS OF NEUTROPHIL ELASTASE ACTIVITY
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This invention relates to substituted bicyclic dihydropyrimidinones of formula 1 and their use as inhibitors of neutrophil elastase activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of pulmonary, gastrointestinal and genitourinary diseases, inflammatory diseases of the skin and the eye and other autoimmune and allergic disorders, allograft rejection, and oncological diseases.
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Page/Page column 87
(2016/03/29)
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- Cesium fluoride catalyzed Aza-Michael addition reaction in aqueous media
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A green approach to the Aza-Michael addition reaction between an amine and α,β-unsaturated compounds has been achieved by conventional as well as non-conventional methods. The reaction is catalyzed by cesium fluoride (CsF) in aqueous media at ambient temperature to afford the product in excellent yield. Ultrasound irradiation has been used as a non-conventional energy source, which reduces the reaction time with improved product yield.
- Labade, Vilas B.,Pawar, Shivaji S.,Shingare, Murlidhar S.
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experimental part
p. 1055 - 1059
(2012/07/27)
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- BISPHOSPHONATE COMPOUNDS FOR CHELATING RADIONUCLIDES
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Bisphosphonate compounds for chelating radionuclides are described which have separate bisphosphonate and metal chelating groups joined by a linker, so that the bisphosphonate groups are available to complex to hydroxyapatite in bone, while the metal chelating group binds to the radionuclide. This avoids problems in the prior art, where the bisphosphonate groups are used for both binding functions which compromises the bone-seeking activity of the bisphosphonate groups when they are used to chelate the radionuclide.
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Page/Page column 42; 43
(2010/11/03)
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- RENIN INHIBITORS
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The present invention is directed to aspartic protease inhibitors. The present invention is also directed to pharmaceutical compositions comprising the disclosed aspartic protease inhibitors. The present invention is further directed to methods of antagon
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Page/Page column 95
(2009/01/23)
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- HYDROXY PYRIDOPYRROLOPYRAZINE DIONE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS
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Hydroxy-substituted pyridopyrrolopyrazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I): (I) wherein a, b, A, B, R1, R2, R3, R4, R5, R6, R7 and R8 are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
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Page/Page column 69-70
(2010/02/11)
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- Method of treating a patient having precancerous lesions with phenyl cycloamino pyrimidinone derivatives
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Derivatives of Phenyl Cycloamino Pyrimidinone are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit growth of neoplastic cells.
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- PYRIDOPYRIMIDINONE ANTIANGINAL AGENTS
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Compounds of the formula and pharmaceutically acceptable salts thereof, wherein R 1 is H, C 1 -C 4 alkyl CN or CONR 4 R 5 ; R 2 is C 2 -C 4 alkyl; R 3 is SO 2 NR 6 R 7, NO 2, NH 2, NHCOR 8 NHSO 2 R 8 or N(SO 2 R 8) 2 ; R 4 and R 5 are each independently selected from H and C 1 -C 4 alkyl; R 6 and R 7 are each independently selected from H and C 1 -C 4 alkyl optionally substituted with CO 2 R 9, OH, pyridyl 5-isoxazolin-3-onyl, morpholino or 1-imidazolidin-2-onyl; or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, morpholino, 1-pyrazolyl or 4-(NR 10)-1-piperazinyl group wherein any of said groups may optionally be substituted with one or two substituents selected from C 1 -C 4 alkyl, CO 2 R 9, NH 2 and OH; R 8 is C 1 -C 4 alkyl or pyridyl; R 9 is H or C 1 -C 4 alkyl; and R 10 is H, C 1 -C 4 alkyl or (hydroxy) C 2 -C 3 alkyl; are selected cGMP PDE inhibitors useful in the treatment of, inter alia, cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis
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- Synthesis of pyrroloazepines. Facile synthesis of 2-substituted pyrrole derivatives by the phosgene method
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A highly convenient method for the synthesis of 2-substituted pyrrole derivatives 7a-c from pyrrole using phosgene was developed. Successively, 7-methyl-6,7-dihydro-1H,5H-pyrrolo[2,3-c]azepine-4,8-dione 1a and 6,7-dihydro-1H,5H-pyrrolo[2,3-c]azepine-4,8-dione 1b (aldisin) were synthesized by phosphorus pentoxide/methanesulfonate and polyphosphoric acid cyclization.
- Cho, Hidetsura,Matsuki, Shinsuke,Mizuno, Akira,Annoura, Hirokazu,Tatsuoka, Toshio
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- 6,7-dihydropyrrol[3,4-c]pyrido[2,3-d]pyrimidine derivatives
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The present invention concerns compounds of the formula: STR1 wherein R is a lower alkyl group, an aryl group or an alkylaryl group and X and Y are the same or different, and each is OH, NH2, or SH. The aryl group or the aryl moiety of the alkylaryl group may be unsubstituted, monosubstituted, disubstituted or trisubstituted. If substituted, each substituent may independently be an alkyl group, an alkyloxy group or a halogen. The present invention also provides methods for synthesizing the compounds described above.
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- Monoalkylaminomethylation d'organometalliques a l'aide de N-alkyl N-trimethylsilyl alkoxymethylamines
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The simple or functional N-alkyl-N-trimethylsilylalkoxymethylamines are very convenient new reagents for the route to unsymmetrical secondary functional amines from organometallic compounds (M=Al, Mg, Zn) prepared from α-unsaturated halides, functional terminal alkynes or α-bromoesters (or amides).
- Courtois, G.,Miginiac, L.
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p. 127 - 142
(2007/10/02)
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- Antidepressive and analgesic 4-aryloxy- and 4-arylthio-3-phenylpiperidines
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Novel 4-aryloxy- and 4-arylthio-3-phenylpiperidines and related compounds, physiologically acceptable salts thereof and intermediates therefor possessing analgesic, antidepressant properties, and a process for the preparation of such compounds, derivatives and intermediates are described.
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- Antidepressant and analgesic 4-aryloxy- and 4-arylthio-3-phenylpiperidines
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Novel 4-aryloxy- and 4-arylthio-3-phenylpiperidines and related compounds, physiologically acceptable salts thereof and intermediates therefor possessing analgesic, antidepressant properties, and a process for the preparation of such compounds, derivatives and intermediates are described.
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- The Conformational Analysis of Saturated Heterocycles. Part 100. 1-Oxa-3-azacyclohexanes
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Conformational equilibria and barriers to ring and nitrogen inversion are determined by 1H and 13C n.m.r. for 13 1-oxa-3-azacyclohexanes and correlated with recent work on the conformational analysis of saturated heterocycles.
- Katritzky, Alan R.,Baker, Victor J.,Brito-Palma, Fernando M. S.
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p. 1739 - 1745
(2007/10/02)
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- Nucleoside Syntheses, XXI. Synthesis of 5-Methylaminomethyl-2-thiouridine, a Rare Nucleoside from t-RNA
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The synthesis of 5-methylaminomethyl-2-thiouridine (1), a rare nucleoside from t-RNA, starting from the appropriate 2-thiouracil and ribose derivatives is described.During the silyl Hilbert-Johnson nucleoside synthesis with silver perchlorate the tert-butoxycarbonyl (Boc) aminoprotecting group in the 2-thiouracil moiety is removed.This cleavage is due to the intermediate formation of trimethylsilyl perchlorate.Preparative applications of this new type of Lewis acids are mentioned.
- Vorbrueggen, Helmut,Krolikiewicz, Konrad
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p. 1438 - 1447
(2007/10/02)
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- Ergoline congeners as potential inhibitors of prolactin release. 3. Derivatives of 3 phenylpiperidine
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In a continuation of attempts to elucidate the prolactin release inhibiting pharmacophore within the ergoline structure, the authors have prepared several derivatives of 3 phenylpiperidine. These congeners have been evaluated for inhibition of prolactin r
- Rusterholz,Barfknecht,Clemens
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