- 6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS
-
The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.
- -
-
Paragraph 0272; 0276; 0932-0933
(2021/11/13)
-
- NITROGEN HETEROCYCLIC COMPOUNDS AND METHODS OF USE
-
The present disclosure relates to compounds of formula (I): and pharmaceutically acceptable salts and stereoisomers thereof. The present disclosure also relates to methods of preparing the compounds, compositions comprising the compounds, and methods of using the compounds as inhibitors of receptor tyrosine kinases, in particular oncogenic mutants of ErbB-receptors e.g. in the treatment of cancer.
- -
-
Paragraph 1808; 1922
(2021/06/26)
-
- INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR KINASES
-
Provided herein are heteroaryl inhibitors of fibroblast growth factor receptor kinases, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
- -
-
Paragraph 00758
(2021/12/30)
-
- PYRROLO(PYRAZOLO)PYRIMIDINE DERIVATIVE AS LRRK2 INHIBITOR
-
The present invention relates to a pyrrolo(pyrazolo)pyrimidine derivative having efficacy as an LRRK2 inhibitor, a preparation method therefor, and a pharmaceutical composition for preventing or treating degenerative brain diseases, containing the same.
- -
-
Paragraph 0119-0120; 0126-0127
(2020/11/23)
-
- Novel pyrrolidine or piperidine derivatives having activity for T-type calcium channel
-
A pyrrolidine or piperidine compound having activity for T - type calcium channel, wherein the pyrrolidine or piperidine compound of Formula 1 according to the present invention has an excellent antagonistic activity to, T-type calcium channel, and can be used as a preventive or therapeutic agent, for pain diseases, or cancer related to cancer, or cancer such as, epilepsy and,hepatic pain, angina. (by machine translation)
- -
-
Paragraph 0379-0382
(2020/04/23)
-
- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
- -
-
Paragraph 00537
(2020/07/06)
-
- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
- -
-
Paragraph 00230; 00666; 00672
(2020/07/05)
-
- Structure-Based Design of a Bromodomain and Extraterminal Domain (BET) Inhibitor Selective for the N-Terminal Bromodomains That Retains an Anti-inflammatory and Antiproliferative Phenotype
-
The bromodomain and extraterminal domain (BET) family of epigenetic regulators comprises four proteins (BRD2, BRD3, BRD4, BRDT), each containing tandem bromodomains. To date, small molecule inhibitors of these proteins typically bind all eight bromodomains of the family with similar affinity, resulting in a diverse range of biological effects. To enable further understanding of the broad phenotype characteristic of pan-BET inhibition, the development of inhibitors selective for individual, or sets of, bromodomains within the family is required. In this regard, we report the discovery of a potent probe molecule possessing up to 150-fold selectivity for the N-terminal bromodomains (BD1s) over the C-terminal bromodomains (BD2s) of the BETs. Guided by structural information, a specific amino acid difference between BD1 and BD2 domains was targeted for selective interaction with chemical functionality appended to the previously developed I-BET151 scaffold. Data presented herein demonstrate that selective inhibition of BD1 domains is sufficient to drive anti-inflammatory and antiproliferative effects.
- Wellaway, Christopher R.,Bamborough, Paul,Bernard, Sharon G.,Chung, Chun-Wa,Craggs, Peter D.,Cutler, Leanne,Demont, Emmanuel H.,Evans, John P.,Gordon, Laurie,Karamshi, Bhumika,Lewis, Antonia J.,Lindon, Matthew J.,Mitchell, Darren J.,Rioja, Inmaculada,Soden, Peter E.,Taylor, Simon,Watson, Robert J.,Willis, Rob,Woolven, James M.,Wyspiańska, Beata S.,Kerr, William J.,Prinjha, Rab K.
-
p. 9020 - 9044
(2020/08/24)
-
- (S)-N-methyl-N-(pyrrolidin-3-yl)acetamide dihydrochloride and synthesis method therefor
-
The invention discloses (S)-N-methyl-N-(pyrrolidin-3-yl)acetamide dihydrochloride and a synthesis method therefor and belongs to the technical field of organic chemical synthesis. The synthesis methodcomprises the following procedures: subjecting (R)-3-pyridonyl-1-tert-butyl carboxylate, which serves as a raw material, to reactions of four steps, i.e., methanesulfonate synthesis, methyl amination, acetyl loading and tert-butyloxycarbonyl removing salt forming, thereby obtaining the (S)-N-methyl-N-(pyrrolidin-3-yl)acetamide dihydrochloride. The synthesis method for the (S)-N-methyl-N-(pyrrolidin-3-yl)acetamide dihydrochloride, provided by the invention, is safe, convenient and economical, the obtained (S)-N-methyl-N-(pyrrolidin-3-yl)acetamide dihydrochloride is stable in performance and can be conveniently stored and transported.
- -
-
Paragraph 0026-0028; 0032-0034; 0038-0040
(2019/07/04)
-
- SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS
-
Provided herein are compounds of the Formula I: (I) or pharmaceutically acceptable salt or solvate thereof, wherein A, B, X1, X2, X3, X4, Ring D, E, Ra, Rb, n and m have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.
- -
-
Paragraph 001372; 001373; 001374
(2018/04/27)
-
- Synthesis and biological evaluation of pyrrolidine-based T-type calcium channel inhibitors for the treatment of neuropathic pain
-
The treatment of neuropathic pain is one of the urgent unmet medical needs and T-type calcium channels are promising therapeutic targets for neuropathic pain. Several potent T-type channel inhibitors showed promising in vivo efficacy in neuropathic pain a
- Yang, Hak Kyun,Son, Woo Seung,Lim, Keon Seung,Kim, Gun Hee,Lim, Eun Jeong,Gadhe, Changdev G.,Lee, Jae Yeol,Jeong, Kyu-Sung,Lim, Sang Min,Pae, Ae Nim
-
p. 1460 - 1471
(2018/09/26)
-
- COMPOUNDS CONTAINING A SULFONIC GROUP AS KAT INHIBITORS
-
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
- -
-
Paragraph 0366; 0367; 0368; 0369
(2018/06/21)
-
- COMPOUNDS
-
Disclosed are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis(ALS).
- -
-
Page/Page column 187
(2017/02/09)
-
- BIARYL DERIVATIVE AS GPR120 AGONIST
-
The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.
- -
-
Paragraph 0547
(2017/11/17)
-
- THERAPEUTIC AGENT FOR FGFR INHIBITOR-RESISTANT CANCER
-
The problem to be solved by the present invention is to provide an anticancer agent for treating tumors resistant to other antitumor agents that inhibit FGFR, and a method for treating such tumors. The present invention provides an antitumor agent for administration to a tumor patient resistant to an FGFR inhibitor, the antitumor agent comprising a 3,5-disubstituted benzene alkynyl compound represented by Formula (I) below or a salt thereof. The present invention also provides a therapeutic method using the anticancer agent.
- -
-
Paragraph 0287
(2016/06/06)
-
- ANTITUMOR DRUG FOR INTERMITTENT ADMINISTRATION OF FGFR INHIBITOR
-
The problem to be solved by the present invention is to provide a potent and highly selective novel FGFR inhibitor, and an antitumor agent having reduced side effects, such as increased blood phosphorus levels, while maintaining the antitumor effect of the FGFR inhibitor. The present invention provides an antitumor agent comprising a 3,5-disubstituted benzene alkynyl compound represented by Formula (I) or a salt thereof that is used so that the 3,5-disubstituted benzene alkynyl compound or a salt thereof is administered on an administration schedule of at least twice a week and a dosing interval of at least one day.
- -
-
Paragraph 0289
(2016/08/07)
-
- Design and synthesis of water soluble β-aminosulfone analogues of SCH 900229 as γ-secretase inhibitors
-
In this paper we describe our strategy to improve the aqueous solubility of SCH 900229, a potent PS1-selective γ-secretase inhibitor for the treatment of Alzheimer's disease. Incorporation of ionizable amino groups into the side chain terminal generates w
- Wu, Wen-Lian,Burnett, Duane A.,Clader, John,Greenlee, William J.,Jiang, Qin,Hyde, Lynn A.,Del Vecchio, Robert A.,Cohen-Williams, Mary E.,Song, Lixin,Lee, Julie,Terracina, Giuseppe,Zhang, Qi,Nomeir, Amin,Parker, Eric M.,Zhang, Lili
-
p. 5836 - 5841
(2016/11/28)
-
- NOVEL FUSED PYRIMIDINE COMPOUND OR SALT THEREOF
-
Provided is a novel compound having BTK inhibitory action and a cell proliferation suppressing effect. Also provided is a medicine useful for the prevention and/or treatment of a disease associated with BTK, particularly cancer, based on BTK inhibitory ac
- -
-
Paragraph 0333
(2015/12/08)
-
- POLYCYCLIC DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
-
Disclosed in the present invention are polycyclic derivatives as represented by general formula (I), the preparation method thereof, pharmaceutical compositions containing the derivatives and uses thereof as therapeutic agents, especially the GPR40 agonist and in preparation of drugs for treating diseases such as diabetes and metabolic disorders, etc., wherein each substituent in the general formula (I) has the same definition as in the description.
- -
-
-
- POLYCYCLIC DERIVATIVES, PREPARATION METHOD AND MEDICAL USES THEREOF
-
Disclosed in the present invention are polycyclic derivatives as represented by general formula (I), the preparation method thereof, pharmaceutical compositions containing the derivatives and uses thereof as therapeutical agents, especially the GPR40 agonist and in preparation of drugs for treating diseases like diabetes and metabolic disorders, etc., wherein each substituent in the general formula (I) has the same definition as in the description.
- -
-
-
- 3,5-DISUBSTITUTED ALKYNYLBENZENE COMPOUND AND SALT THEREOF
-
The present invention provides a compound represented by Formula (I) (wherein R1, X1, X2, Y, and Z are as defined in the specification), or a salt thereof.
- -
-
Paragraph 0196
(2013/11/19)
-
- SUBSTITUTED CYCLIC COMPOUNDS AND METHODS OF USE
-
The present invention provides novel substituted cyclic compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
- -
-
Paragraph 0199
(2013/09/26)
-
- GAMMA SECRETASE INHIBITORS
-
Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing t
- -
-
Page/Page column 35
(2012/10/18)
-
- PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
-
Compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the compounds and using the com
- -
-
Page/Page column 75
(2012/05/31)
-
- ARYLVINYLAZACYCLOALKANE COMPOUNDS FOR CONSTIPATION
-
The present invention relates to methods of treating constipation and enhancing colonic motility by administration of 5-((E)-2 pyrrolidin-3-ylvinyl)pyrimidine or a pharmaceutically acceptable salt thereof.
- -
-
Page/Page column 28
(2011/10/05)
-
- FUSED HETEROCYCLIC COMPOUND
-
The present invention relates to a fused heterocyclic compound having the Formula 1, which is useful as a platelet aggregation inhibitor, a method for preparing the same, and a pharmaceutical composition for inhibiting platelet aggregation comprising the same.
- -
-
Page/Page column 43
(2011/07/29)
-
- HETEROCYCLOALKYL-CONTAINING THIENOPYRIMIDINES FOR PHARMACEUTICAL COMPOSITIONS
-
The present invention relates to novel pharmaceutical compositions comprising thienopyrimidine compounds. Moreover, the present invention relates to the use of the thienopyrimidine compounds of the invention for the production of pharmaceutical compositio
- -
-
Page/Page column 72-73
(2011/09/30)
-
- HETEROCYCLOALKYL-CONTAINING THIENOPYRIMIDINES FOR PHARMACEUTICAL COMPOSITIONS
-
The present invention relates to novel pharmaceutical compositions comprising thienopyrimidine compounds. Moreover, the present invention relates to the use of the thienopyrimidine compounds of the invention for the production of pharmaceutical compositio
- -
-
Page/Page column 28
(2011/09/20)
-
- CARBAPENEM ANTIBACTERIALS WITH GRAM-NEGATIVE ACTIVITY
-
The present invention provides β-methyl carbapenem compounds and pharmaceutical compositions useful in the treatment of bacterial infections and methods for treating such infections using such compounds and/or compositions. The invention includes administering an effective amount of a carbapenem compound or salt and/or prodrug thereof to a host in need of such a treatment.
- -
-
-
- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1, 2-A]PYRIDINE-3- CARBOXAMIDE COMPOUNDS AS CFMS INHIBITORS
-
Compounds of Formula (I): and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4 and R5 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases and pain.
- -
-
Page/Page column 97
(2011/07/09)
-
- FUSED RING HETEROARYL KINASE INHIBITORS
-
Provided herein are fused ring heteroaryl compounds useful in a variety of methods, including reducing the activity of certain kinases and treating certain disease states.
- -
-
Page/Page column 73
(2010/04/30)
-
- NOVEL COMPOUNDS
-
The present invention relates to compounds that bind to and modulate the activity of neuronal nicotinic acetylcholine receptors, to novel salts thereof, to processes for preparing these compounds, novel chemical compounds useful as intermediates, pharmaceutical compositions containing the product compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central nervous system (CNS).
- -
-
Page/Page column 30
(2010/06/20)
-
- SYNTHESIS AND NOVEL SALT FORMS OF (R)-5-((E)-2-(PYRROLIDIN-3-YLVINYL)PYRIMIDINE
-
The present invention relates to the stereospecific synthesis of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, its salt forms, and novel polymorphic forms of these salts.
- -
-
Page/Page column 33
(2010/06/20)
-
- N-SUBSTITUTED SATURATED HETEROCYCLIC SULFONE COMPOUNDS WITH CB2 RECEPTOR AGONISTIC ACTIVITY
-
This invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein X, R1, R2,R3, R4, R5, R6, R7, k, m, n, p, q, r and s are each as described herein, and compositions containing such compounds, and the use of such compounds in the treatment of a condition mediated by CB2 receptor activity.
- -
-
Page/Page column 86-87
(2010/08/08)
-
- Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2
-
The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH2; EM1 and Tyr-Pro-Phe-Phe-NH2; EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH 2) exhibit an extremely high selectivity for μ-opioid receptor. Here a series of novel EM2 and morphiceptin analogues containing in place of the proline at position 2 the S and R residues of β-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3- pyrrolidinesulphonic acid (βPrs) have been synthesized and their binding affinity and functional activity have been investigated. The highest μ-receptor affinity is shown by [(S)βPrs2]EM2 analogue (6e) which represents the first example of a β-sulphonamido analogue in the field of opioid peptides.
- Giordano, Cesare,Sansone, Anna,Masi, Annalisa,Lucente, Gino,Punzi, Pasqualina,Mollica, Adriano,Pinnen, Francesco,Feliciani, Federica,Cacciatore, Ivana,Davis, Peg,Lai, Josephine,Ma, Shou-Wu,Porreca, Frank,Hruby, Victor
-
scheme or table
p. 4594 - 4600
(2010/10/19)
-
- PROCESS FOR PRODUCING ESTER OR ALCOHOL
-
Provided is a process for producing an ester or alcohol using a fluoroimidinium sulfonate derivative represented by the general formula (9) or a fluoroimidinium carboxylate derivative represented by the general formula (6) and using as a raw material alcohol involving inversion of steric configuration. Further provided are a fluoroimidinium sulfonate derivative represented by the general formula (9), and a process for producing the same.
- -
-
Page/Page column 37-38
(2009/04/23)
-
- PHENOXY-PYRROLIDINE DERIVATIVE AND ITS USE AND COMPOSITIONS
-
The present invention is directed to the compound 2-(4- (hydroxymethyl)phenoxy)-1 -(3-(2-(trifluoromethyl)phenoxy)pyrrolidin-1 -yl)ethanone, its use as an inhibitor of stearoyl CoA desaturase and to pharmaceutical compositions containing this compound.
- -
-
Page/Page column 19
(2009/04/25)
-
- Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors
-
Potent SAH analogues with constrained homocysteine units have been designed and synthesized as inhibitors of human DNMT enzymes. The five membered (2S,4S)-4-mercaptopyrrolidine-2-carboxylic acid, in 1a, was a good replacement for homocysteine, while the corresponding six-member counterpart was less active. Further optimization of 1a, changed the selectivity profile of these inhibitors. A Chloro substituent at the 2-position of 1a, compound 1d, retained potency against DNMT1, while N6 alkylation, compound 7a, conserved DNMT3b2 activity. The concomitant substitutions of 1a at both 2- and N6 positions reduced activity against both enzymes.
- Isakovic, Ljubomir,Saavedra, Oscar M.,Llewellyn, David B.,Claridge, Stephen,Zhan, Lijie,Bernstein, Naomy,Vaisburg, Arkadii,Elowe, Nadine,Petschner, Andrea J.,Rahil, Jubrail,Beaulieu, Norman,Gauthier, France,MacLeod, A. Robert,Delorme, Daniel,Besterman, Jeffrey M.,Wahhab, Amal
-
scheme or table
p. 2742 - 2746
(2010/03/03)
-
- Novel analogues of istaroxime, a potent inhibitor of Na+,K +-ATPase: Synthesis and structure-activity relationship
-
We report the synthesis and biological properties of novel inhibitors of the Na+,K+-ATPase as positive inotropic compounds. Following our previously described model from which Istaroxime was generated, the 5α,14α-androstane skeleton was used as a scaffold to study the space around the basic chain of our lead compound. Some compounds demonstrated higher potencies than Istaroxime on the receptor and the (E)-3-[(R)-3- pyrrolidinyl]oxime derivative, 15, was the most potent; as further confirmation of our model, the E isomers of the oxime are more potent than the Z form. The compounds tested in the guinea pig model induced positive inotropic effects, which are correlated to the in vitro inhibitory potency on the Na +,K+-ATPase. The finding that all tested compounds resulted less proarrhythmogenic than digoxin, a currently clinically used positive inotropic agent, suggests that this could be a feature of the 3-aminoalkyloxime derivative class of 5α,14α-androstane.
- Gobbini, Mauro,Armaroli, Silvia,Banfi, Leonardo,Benicchio, Alessandra,Carzana, Giulio,Fedrizzi, Giorgio,Ferrari, Patrizia,Giacalone, Giuseppe,Giubileo, Michele,Marazzi, Giuseppe,Micheletti, Rosella,Moro, Barbara,Pozzi, Marco,Scotti, Piero Enrico,Torri, Marco,Cerri, Alberto
-
supporting information; experimental part
p. 4601 - 4608
(2009/06/06)
-
- NOVEL AZACYCLY-SUBSTITUTED ARYLTHIENOPYRIMIDINONES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
-
The invention relates to azacyclyl-substituted arylthienopyrimidinones and their derivatives of formula (I), and their physiologically tolerated salts and physiologically functional derivatives, their preparation, medicaments comprising at least one azacyclyl-substituted arylthienopyrimidinone of the invention or its derivative, and the use of the azacyclyl-substituted aryithienopyrimidinones of the invention and their derivatives as MCH antagonists.
- -
-
Page/Page column 88
(2008/06/13)
-
- MUSCARINIC RECEPTOR AGONISTS THAT ARE EFFECTIVE IN THE TREATMENT OF PAIN, ALZHEIMER'S DISEASE AND SCHIZOPHRENIA
-
Compounds of Formula IA, or pharmaceutically acceptable salts thereof: IA wherein G1, G2, G3, G4, R1, R2, X, Y, Z and n are as defined in the specification as well as salts and pharmaceutic
- -
-
Page/Page column 53-54
(2008/06/13)
-
- DERIVATIVES FOR MODULATION OF ION CHANNELS
-
Sulfonamide derivatives act as ion channel antagonists. These compounds have the general Formula (I): Formula (I) compositions are useful for treating or relieving pain-related conditions.
- -
-
Page/Page column 59
(2010/11/27)
-
- Synthesis of racemic and enantiomeric 3-pyrrolidinyl derivatives of nucleobases
-
The synthesis of novel 3-pyrrolidinyl derivatives of nucleobases is described. Starting from malic acid, we improved the synthesis of both racemic and optically active N-benzyl-3-hydroxypyrrolidine-2,5-diones, which were transformed in four steps into N-tert-butyloxycarbonyl-3-mesyloxypyrrolidines, the key synthons for the alkylation of purine and pyrimidine nucleobases. Alkylations of cesium salts of purines and sodium salts of pyrimidines with N-tert-butyloxycarbonyl-3-mesyloxypyrrolidines proceeded smoothly, giving high yields of 9-substituted purine derivatives and moderate yields of 1-substituted pyrimidine derivatives. Using (S)-N-tert-butyloxycarbonyl-3-mesyloxypyrrolidine as the same intermediate for the synthesis of both enantiomeric N-Boc-3-pyrrolidinyladenines, and considering the results obtained on chiral HPLC analysis of the products, we proved that nucleophilic displacement of the mesyloxy group proceeded with inversion and not with retention of the configuration. Prepared compounds were tested for cytostatic and antiviral properties, but no significant activity was found.
- Ko?alka, Petr,Pohl, Radek,Rejman, Dominik,Rosenberg, Ivan
-
p. 5763 - 5774
(2007/10/03)
-
- Synthesis of racemic and enantiomeric 3-pyrrolidinyl derivatives of purine and pyrimidine nucleobases
-
The present work relates to the synthesis of pyrrolidine nucleoside analogs. Starting from malic acid, we have elaborated a high-yield synthesis of racemic and enantiomeric N-protected 3-pyrrolidinols and their O-mesyl derivatives as key compounds for alk
- Kocalka, Petr,Pohl, Radek,Rejman, Dominik,Rosenberg, Ivan
-
p. 805 - 808
(2007/10/03)
-
- 3-AMINOPYRROLIDINES AS INHIBITORS OF MONOAMINE UPTAKE
-
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful for the inhibition of the uptake of one or more physiologically active monoamines (serotonin, norepinephrine, and dopamine).
- -
-
Page/Page column 61
(2008/06/13)
-
- TREATMENT OF LEARNING DISABILITIES AND MOTOR SKILLS DISORDER WITH NOREPINEPHRINE REUPTAKE INHIBITORS
-
Provided are methods and medicaments for treating a learning disability or a Motor Skills Disorder, comprising administering to a patient in need of such treatment an effective amount of a selective norepinephrine reuptake inhibitor.
- -
-
Page/Page column 221
(2010/02/11)
-
- TREATMENT OF PERVASIVE DEVELOPMENTAL DISORDERS WITH NOREPINEPHRINE REUPTAKE INHIBITORS
-
Provided are methods and medicaments for treating a Pervasive Developmental Disorder, comprising administering to a patient in need of such treatment an effective amount of a selective norepinephrine reuptake inhibitor.
- -
-
Page/Page column 224
(2010/02/11)
-
- TREATMENT OF HOT FLASHES, IMPULSE CONTROL DISORDERS AND PERSONALITY CHANGE DUE TO A GENERAL MEDICAL CONDITION
-
Selective norepinephrine reuptake inhibitors are useful for the prevention or treatment of hot flashes, vasomotor symptoms, impulse control disorders or personality change due to a general medical condition.
- -
-
Page/Page column 223
(2010/02/12)
-
- Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1- yl)ethyl]indoles: Potent agonists for the h5-HT(1D) receptor with high selectivity over the h5-HT(1B) receptor
-
The design, synthesis, and biological evaluation of a novel series of 3- [2-(pyrrolidin-1-yl)ethyl]-indoles with excellent selectivity for h5-HT(1D) (formerly 5-HT(1Dα)) receptors over h5-HT(1B) (formerly 5-HT(1Dβ)) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT(1D) and h5-HT(1B) receptors. The differential expression of h5-HT(1D) and h5-HT(1B) receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT(1D) subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT(1D) over h5-HT(1B) receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT(1D) receptor and 100-fold selectivity with respect to h5-HT(1B) receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT(1D) subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPγS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT(1D) and h5-HT(1B) receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT(1D) receptor domain which is absent for the h5-HT(1B) receptor. The compounds described herein will be important tools to delineate the role of h5-HT(1D) receptors in migraine.
- Sternfeld, Francine,Guiblin, Alexander R.,Jelley, Richard A.,Matassa, Victor G.,Reeve, Austin J.,Hunt, Peter A.,Beer, Margaret S.,Heald, Anne,Stanton, Josephine A.,Sohal, Bindi,Watt, Alan P.,Street, Leslie J.
-
p. 677 - 690
(2007/10/03)
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- Synthesis and structure-activity relationships of 1β-methylcarbapenems with quaternary ammonium side chains
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The synthesis and antibacterial activity of 1β-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied. Two types of new carbapenem derivatives have been synthesized. These 1β-methylcarbapenems, one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio-4-ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-ylcarbon-yl)pyrrolidin-4 -ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.
- Ishikawa, Katsuya,Kojima, Katsuhiko,Miyauchi, Masao,Endo, Rokuro,Yasuda, Hiroshi,Kawamoto, Isao
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p. 757 - 770
(2007/10/03)
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