cas 375853-82-0, 1,2,3,6-TETRAHYDROPYRIDINE-4-YL-BORONIC ACID PINACOL ESTER

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AZAINDOLE DERIVATIVE AND USE THEREOF AS FGFR AND C-MET INHIBITOR
A series of pyrazolopymidine derivatives, and use thereof in the preparation of a medicament for treating disease associated with FGFR and c-Met. The pyrazolopymidine derivative is a compound represented by formula (I), a tautomer, or a pharmaceutically acceptable salt thereof.
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Paragraph 0204-0205

(2021/05/29)

COMPOUNDS FOR TARGETED DEGRADATION OF BRD9
BRD9 protein degradation compounds or pharmaceutically acceptable salts thereof are provided for the treatment of disorders mediated by BRD9, including but not limited to abnormal cellular proliferation.
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Page/Page column 551-552; 627; 629

(2021/09/11)

METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION
Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
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Paragraph 0185

(2022/01/06)

Synthesis method of N-methyl-1, 2, 5, 6-tetrahydropyridine-4-boronic acid pinacol ester
The invention belongs to the field of synthesis of medical intermediates, and particularly relates to a synthesis method of N-methyl-1, 2, 5, 6-tetrahydropyridine-4-boronic acid pinacol ester. According to the method, N-Boc-1, 2, 5, 6-tetrahydropyridine-4-boronic acid pinacol ester is selected as a raw material, Boc protection is removed under an acidic condition, paraformaldehyde, a reducing reagent and HOBt are added for an N-methylation reaction, the method can effectively inhibit the occurrence of quaternary ammonium salt side reactions, the post-treatment is simple, and the method is suitable for industrial production. The crude product is recrystallized to obtain the N-methyl-1, 2, 5, 6-tetrahydropyridine-4-boronic acid pinacol ester product with the purity of more than 98.0%, and the two-step molar yield is more than 90%.
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Paragraph 0022-0023; 0025-0026; 0028-0029; 0031-0032; 0034

(2020/04/09)

MACROCYCLIC AZOLOPYRIDINE DERIVATIVES AS EED AND PRC2 MODULATORS
The invention relates to modulators of Embryonic Ectoderm Development (EED) and/or Polycomb Repressive Complex 2 (PRC2) useful in the treatment of disorders and diseases associated with EEC and PRC2, being macrocyclic azolopyridine derivatives and compositions thereof of Formula (I), or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, enantiomer, isomer, or tautomer thereof, wherein X1, X2, X3, A1, A2, Y, R1, R2, R3, and R4 are as described herein.
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Paragraph 1265

(2020/10/09)

Preparation method of N-substituted-tetrahydropyridine-3/4-boric acid/ester
The invention discloses a preparation method of N-substituted tetrahydropyridine-3/4-boric acid/ester, and belongs to the technical field of organic boric acid chemistry. The method comprises the following steps: carrying out a reaction on pyridine-3/4-boric acid/ester and a halide to form a quaternary salt, and reducing the quaternary salt with sodium/potassium borohydride in an aprotic solvent to generate N-substituted-tetrahydropyridine-3/4-boric acid/ester. According to the method, easily-synthesized pyridine-3/4-boric acid/ester is used as a raw material, the product can be obtained through two continuous steps, and the reaction selectivity is high, so that the defect that palladium-catalyzed coupling or ultralow temperature is needed when substituted piperidone is adopted as a raw material is overcome, the method is verified on the hectogram scale, and a concise and efficient synthesis path is provided for preparation of the compound.
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(2020/04/22)

Tetrahydroisoquinoline amide compounds containing quaternary ammonium ion and pharmaceutical use thereof
The invention relates to tetrahydroisoquinoline amide compounds containing quaternary ammonium ion, a preparation method of the compounds, and a use of the compounds in the treatment or prevention ofthromboembolic diseases.
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Paragraph 0333-0336

(2019/07/11)

Pyrrolopyrazole derivative and preparation method thereof, and applications of pyrrolopyrazole derivative in medicine
The present invention relates to a pyrrolopyrazole derivative and a preparation method thereof, and applications of the pyrrolopyrazole derivative in medicine, particularly to a class of new pyrrolopyrazole derivatives represented by a general formula (I), and a preparation method thereof, and uses of the pyrrolopyrazole derivatives or pharmaceutical compositions containing the pyrrolopyrazole derivatives as treating agents, particularly as gastric acid secretion inhibitors and potassium ion competitive acid blockers (P-CABs) in biomedicine, wherein various substituents (R, R and R) and the groups (X, Y and Z) in the formula (I) are defined in the specification.
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Paragraph 0098; 0099

(2019/09/14)

New synthesis method of N-substituted-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester
The invention discloses a new synthesis method of N-substituted-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester. The new synthesis method of the N-substituted-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester comprises the following three reaction steps: firstly, performing reaction on 4-bromopyridine hydrochloride and clR1 to prepare 4-bromine-N-substituted-pyridine chloride; then preparing N-substituted-piperidine-4-alkenyl bromide through NaBH4 reduction; finally, preparing the target product N-substituted-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester through a Grignard method and methoxy boric acid ester. The synthesis route has the advantages of high universality, cheap and easily available raw materials, mild reaction condition, few byproducts, high yield andthe like, and the product has high economic property and strong market competitiveness and is suitable for industrialized production. The formula is as shown in the description, wherein R1=-Boc;-Cbz;-Bz;-Bn;-Fmoc;-Me;-Et;-iPr;-Ph.
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Paragraph 0022; 0024-0025

(2019/12/25)

Novel synthesis method of N-Boc-1,2,5,6-tetrahydropyridine-4-boric acid pinacol ester
The invention discloses a novel synthesis method of N-Boc-1,2,5,6-tetrahydropyridine-4-boric acid pinacol ester. The synthesis method comprises following three steps: taking 4-bromopyridine hydrochloride as the primary raw material, reacting 4-bromopyridine hydrochloride with tert-butyl chloroformate or di-tert-butyl bicarbonate to prepare 4-bromo-N-Boc-pyridine chloride; reducing 4-bromo-N-Boc-pyridine chloride by NaBH4 to prepare N-Boc piperidine-4-vinyl bromide; and finally, carrying out coupling reactions between N-Boc piperidine-4-vinyl bromide and bis(pinacolato) diboron to prepare the target product: N-Boc-1,2,5,6-tetrahydropyridine-4-boric acid pinacol ester. The synthesis route has the advantages of easily available raw materials, mild conditions, few byproducts, and high yield, and is suitable for industrial enlarged production.
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(2019/10/02)

Technological method for synthesizing N-substituted-1,2,5,6-tetrahydropyridine-4-boric acid ester
The invention relates to an organic compound synthesis method, in particular to a technological method for synthesizing N-substituted-1,2,5,6-tetrahydropyridine-4-boric acid ester. The method comprises the step that N-substituted-1,2,5,6-tetrahydropyridine-4-halide serves as a raw material to react with bi-boric acid ester, cuprous halide or cuprous oxide, a ligand and organic base in a solvent, so that N-substituted-1,2,5,6-tetrahydropyridine-4-boric acid ester is obtained. The method is innovative, and easy and convenient to operate, the technological route is short, the cost is low, the product purity is high, the reaction conditions are mild, the situation that metal palladium coupling or a high-activity Grignard reagent and a low temperature condition are adopted in a traditional method is avoided, and the method has potential cost advantage, and is suitable for industrialized scale-up production.
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Paragraph 0018

(2019/06/07)

Tetrahydroisoquinoline compound and its preparation method, pharmaceutical composition and use
The invention relates to a tetrahydroisoquinoline compound and its preparation method, pharmaceutical composition and use. The tetrahydroisoquinoline compound is shown by the general formula (1). In the general formula (1), the symbols have the same definitions as in the specification.
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Paragraph 0110

(2018/03/24)

SUBSTITUTED TETRAHYDROPYRIDINE DERIVATIVES AS IDO-1 INHIBITORS AND USES THEREOF
Compounds of formula I that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase, pharmaceutical compositions including such compounds and methods of treating diseases, conditions or disorders utilizing such compounds and compositions.
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Paragraph 0065; 0117

(2018/11/21)

Discovery of 3-Cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist
The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, we identified a molecule displaying promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA and RORB receptor isoforms. Lead optimization to improve the potency and metabolic stability of this hit focused on two key design strategies, namely, iterative optimization driven by increasing lipophilic efficiency and structure-guided conformational restriction to achieve optimal ground state energetics and maximize receptor residence time. This approach successfully identified 3-cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide as a potent and selective RORC2 inverse agonist, demonstrating good metabolic stability, oral bioavailability, and the ability to reduce IL-17 levels and skin inflammation in a preclinical in vivo animal model upon oral administration.
Schnute, Mark E.,Wennerstal, Mattias,Alley, Jennifer,Bengtsson, Martin,Blinn, James R.,Bolten, Charles W.,Braden, Timothy,Bonn, Tomas,Carlsson, Bo,Caspers, Nicole,Chen, Ming,Choi, Chulho,Collis, Leon P.,Crouse, Kimberly,F?rnegardh, Mathias,Fennell, Kimberly F.,Fish, Susan,Flick, Andrew C.,Goos-Nilsson, Annika,Gullberg, Hjalmar,Harris, Peter K.,Heasley, Steven E.,Hegen, Martin,Hromockyj, Alexander E.,Hu, Xiao,Husman, Bolette,Janosik, Tomasz,Jones, Peter,Kaila, Neelu,Kallin, Elisabet,Kauppi, Bj?rn,Kiefer, James R.,Knafels, John,Koehler, Konrad,Kruger, Lars,Kurumbail, Ravi G.,Kyne, Robert E.,Li, Wei,L?fstedt, Joakim,Long, Scott A.,Menard, Carol A.,Mente, Scot,Messing, Dean,Meyers, Marvin J.,Napierata, Lee,N?teberg, Daniel,Nuhant, Philippe,Pelc, Matthew J.,Prinsen, Michael J.,Rh?nnstad, Patrik,Backstr?m-Rydin, Eva,Sandberg, Johnny,Sandstr?m, Maria,Shah, Falgun,Sj?berg, Maria,Sundell, Aron,Taylor, Alexandria P.,Thorarensen, Atli,Trujillo, John I.,Trzupek, John D.,Unwalla, Ray,Vajdos, Felix F.,Weinberg, Robin A.,Wood, David C.,Xing, Li,Zamaratski, Edouard,Zapf, Christoph W.,Zhao, Yajuan,Wilhelmsson, Anna,Berstein, Gabriel
p. 10415 - 10439
(2018/09/20)

COMPOUNDS FOR BINDING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9)
The present disclosure relates to novel compounds, methods, and compositions capable of binding to PCSK9, thereby modulating PCSK9 proprotein convertase enzyme activity. The compounds of the disclosure include compounds Formula (I).
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Paragraph 0192

(2017/09/15)

Process Development and Good Manufacturing Practice Production of a Tyrosinase Inhibitor via Titanium-Mediated Coupling between Unprotected Resorcinols and Ketones
A concise and economically attractive process for the synthesis of a novel tyrosinase inhibitor has been developed and implemented on a multikilogram scale under GMP. A major achievement to the success of the process is the development of a direct coupling between free resorcinol and ketone. First developed under basic conditions, this coupling has been turned to a novel titanium(IV) mediated process allowing good selectivity, easy isolation, and high atom efficiency. Other key steps feature an alkene reduction by palladium catalyzed transfer hydrogenation and a urea formation using N,N′-disuccinimidyl carbonate as the carbonyl source. This route allowed us to produce kilogram batches of the candidate to support preclinical and clinical studies.
Gerfaud, Thibaud,Martin, Cédric,Bouquet, Karinne,Talano, Sandrine,Millois-Barbuis, Corinne,Musicki, Branislav,Boiteau, Jean-Guy,Cardinaud, Isabelle
p. 631 - 640
(2017/04/28)

NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS
The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.
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Paragraph 0264

(2017/02/09)

ANTI-AMYLOID COMPOUNDS CONTAINING BENZOFURAZAN
In general, among other things, compounds of Formula I are provided: in which R11 is e.g., 4-(pyrrolidin-1-yl)piperidin-1-yl, N-methyl-3-(pyrrolidin-1-yl)propan-1-amino, N1,N1,N3-trimethylpropane-1,3-diamino, N,N-dimethylpiperidin-4-amino, 3-(pyrrolidin-1-ylmethyl)azetidin-1-yl, 3-(pyrrolidin-1-ylmethanon)azetidin-1-yl, or 3-(morpholin-1-ylmethyl)azetidin-1-yl; R13 is, e.g., phenyl optionally substituted with one or more substituents; and R12 and R14 are each independently hydrogen or alkyl. Methods of treatment are also provided.
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(2017/07/14)

PYRIMIDINE AND TRIAZINE DERIVATIVES AND THEIR USE AS AXL INHIBITORS
Compounds of the general formula(I): (I) processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
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Page/Page column 51

(2016/07/05)

Synthesis method of N-substituted-1,2,5,6-tetrahydropyridine-4-borate
The invention discloses a synthesis method of N-substituted-1,2,5,6-tetrahydropyridine-4-borate. According to the synthesis method, N-substituted-4-piperidone is taken as the raw material, N-substituted-4-piperidone, triaryl phosphite, halogen, and organic alkali carry out reactions, the carbonyl group is converted into vinyl halogen, and finally the reaction product reacts with isopropyl magnesium chloride-lithium chloride and alkoxyl borate to generate N-substituted-1,2,5,6-tetrahydropyridine-4-borate. The synthesis method has the advantages that the raw materials are easily available, the operation is simple and convenient, the product purity is high, the ultralow temperature condition and palladium catalytic coupling are not needed, the cost is reduced, the route is optimized, and thus the product is competitive in the market.
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Paragraph 0019

(2016/11/17)

Optimization and multigram scalability of a catalytic enantioselective borylative migration for the synthesis of functionalized chiral piperidines
The development of new, efficient and economical methods for the preparation of functionalized, optically enriched piperidines is important in the field of drug discovery where this class of heterocycles is often deemed a privileged structure. We have optimized a Pd-catalyzed enantioselective borylative migration of an alkenyl nonaflate derivative of the simple precursor, N-Boc-4-piperidone. This anomalous borylation reaction lends access to a chiral optically enriched piperidinyl allylic boronate that can be employed in carbonyl allylboration and stereoselective cross-coupling to produce substituted dehydropiperidines related to numerous pharmaceutical agents. A systematic fine-tuning of reaction conditions revealed that diethyl ether and the green solvent cyclopentyl methyl ether are suitable reaction solvents providing the highest enantioselectivity (up to 92% ee) under a low catalyst loading of 3 mol%. Optimization of the aldehyde allylboration step led to higher yields with further solvent economy. The multigram-scalability of the entire process was demonstrated under the reaction conditions that provide optimal atom-economy and efficiency.
Kim, You-Ri,Hall, Dennis G.
supporting information
p. 4739 - 4748
(2016/06/09)

SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
HEDRICK Michael P.,HERSHBERGER Paul M.,MALONEY Patrick R.,PEDDIBHOTLA Satyamaheshwar,PINKERTON Anthony B.
Paragraph 00297; 00586; 00643

(2016/04/26)

Imidazopyrazine Derivatives as Modulators of TNF Activity
A series of imidazo[1,2-α]pyrazine derivatives, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorder; and oncological disorders.
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Paragraph 0474

(2015/07/15)

SUBSTITUTED 2-AMINOPYRIDINE PROTEIN KINASE INHIBITOR
Disclosed are a 2-aminopyridine derivative having protein kinase inhibition activity, a preparation method and a pharmaceutical composition thereof Also disclosed are uses of the compounds and the pharmaceutical compositions thereof in the preparation of drugs for treating and/or preventing protein kinase-related diseases.
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Paragraph 0142

(2015/12/19)

SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
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Paragraph 00727; 00728

(2014/07/08)

IMIDAZOPYRAZINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
A series of imidazo[1,2-α]pyrazine derivatives, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
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Page/Page column 92

(2014/02/15)

Synthesis and biological evaluation of 1-(isoxazol-5-ylmethylaminoethyl)-4- phenyl tetrahydropyridine and piperidine derivatives as potent T-type calcium channel blockers with antinociceptive effect in a neuropathic pain model
New tetrahydropyridinyl and piperidinyl ethylamine derivatives were designed with hypothetical mapping on pharmacophore model generated from ligand-based virtual screening. The designed compounds were synthesized, and their inhibitory activities on T-type calcium channel were assayed using FDSS and patch-clamp assay. Among them, compounds 7b and 10b showed potent T-type calcium current blocking activity against Cav3.1 (α 1G) and Cav3.2 (α1H) channel simultaneously. With hERG and pharmacokinetics studies, compounds 7b and 10b were evaluated for the antinociceptive effect on rat model of neuropathic pain. They were significantly effective in decreasing the pain responses to mechanical and cold allodynia induced by spinal nerve ligation. These results suggest that modulation of α1G and α1H subtype T-type calcium channels may provide a promising approach for the treatment of neuropathic pain.
Lee, Ju-Hyeon,Seo, Seon Hee,Lim, Eun Jeong,Cho, Nam-Chul,Nam, Ghilsoo,Kang, Soon Bang,Pae, Ae Nim,Jeong, Nakcheol,Keum, Gyochang
p. 246 - 257
(2014/02/14)

PIPERIDINYL NAPHTHYLACETIC ACIDS
The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and X are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds of formula I are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
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Paragraph 0167

(2013/06/27)

CHEMOKING RECEPTOR ANTAGONISTS
Disclosed herein are chemokine receptor antagonists of formula (I) wherein G1, X1, X2, and X3 are as defined in the specification. Compositions comprising such compounds; and methods for treating conditions and disorders using such compounds and compositions are also described.
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Page/Page column 113; 114

(2013/03/26)

Concise synthesis and antimalarial activity of all four mefloquine stereoisomers using a highly enantioselective catalytic borylative alkene isomerization
The pluses and minuses of mefloquine: A highly enantioselective catalytic borylative isomerization/aldehyde allylboration method for the stereoselective synthesis of the antimalarial drug mefloquine was optimized, thus leading to an efficient synthesis of all four mefloquine stereoisomers and analogues (see scheme). The absolute configuration of these potent compounds was determined for the first time by using chemical synthesis. Copyright
Ding, Jinyue,Hall, Dennis G.
supporting information
p. 8069 - 8073
(2013/08/23)

PHTALAZINE DERIVATIVES AS JAK1 INHIBITORS
JAK1 inhibitors of structural formula (I), wherein Ar1, Ar2, Q, W, X, Y, and Z are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases.
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Page/Page column 50; 51

(2012/04/04)

SUBSTITUTED FUSED TRICYCLIC COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
The present invention relates to substituted fused tricyclic compounds of formula (I) or (Ia), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, co-crystals, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by JAK activity. The compounds of the present invention are useful in the treatment, prevention or suppression of diseases and disorders mediated by JAK activity. Such conditions include, but not limited to, arthritis, Alzheimer's disease, autoimmune thyroid disorders, cancer, diabetes, leukemia, T-cell prolymphocytic leukemia, lymphoma, myleoproliferation disorders, lupus, multiple myeloma, multiple sclerosis, osteoarthritis, sepsis, psoriatic arthritis, prostate cancer, T-cell autoimmune disease, inflammatory diseases, chronic and acute allograft transplant rejection, bone marrow transplant, stroke, asthma, chronic obstructive pulmonary disease, allergy, bronchitis, viral diseases, or Type I diabetes, complications from diabetes, rheumatoid arthritis, asthma, Crohn's disease, dry eye, uveitis, inflammatory bowel disease, organ transplant rejection, psoriasis and ulcerative colitis. The present disclosure also relates to process for the preparation of such compounds, and to pharmaceutical compositions containing them.
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Page/Page column 98-99

(2012/10/08)

PICOLINAMIDE AND PYRIMIDINE-4-CARBOXAMIDE COMPOUNDS, PROCESS FOR PREPARING AND PHAMACEUTICAL COMPOSITION COMPRISING THE SAME
Provided are picolinamide and pyrimidine-4-carboxamide compounds, a method for preparing the same, a pharmaceutical composition containing the same, and a medical use using the compound as an agent for preventing, regulating, and treating diseases related to regulation of glucocorticoids by using selective inhibitory activity of the compound for an 11β-HSD1 enzyme. The picolinamide and pyrimidine-4-carboxamide compounds of the present invention are selective inhibitors of human-derived 11β-HSD1 enzymes, and are useful in an agent for preventing, regulating, and treating diseases related to glucocorticoid regulation in which human- derived 11β-HSD1 enzymes are involved, for example, metabolic syndromes such as, type 1 and type 2 diabetes, diabetes later complications, latent autoimmune diabetes adult (LAD A), insulin tolerance syndromes, obesity, impaired glucose tolerane (IGT), impaired fasting glucose (IFG), damaged glucose tolerance, dyslipidemia, atherosclerosis, hypertension, etc.
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Page/Page column 42

(2011/11/30)

GPR119 Agonists
GPR119 agonist compounds of the formula: and pharmaceutical compositions for the treatment of diabetes and obesity.
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Page/Page column 6

(2011/02/18)

1-(2-PHENOXYMETHYLHETEROARYL)PIPERIDINE AND PIPERAZINE COMPOUNDS
The invention relates to compounds of formula I: where X, HAr, a, and R1 through R6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
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Page/Page column 17-18

(2011/10/10)

PYRROLIDINYL AND PIPERIDINYL COMPOUNDS USEFUL AS NHE-1 INHIBITORS
Disclosed are compounds of formula (I) and compositions of the present invention which are inhibitors of the sodium proton exchanger isoform-1 (NHE-I). Also disclosed are methods of using and making the same.
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Page/Page column 115-116

(2010/04/03)

4-[2-(2-FLUOROPHENOXYMETHYL)PHENYL]PIPERIDINE COMPOUNDS
The invention relates to compounds of formula I: where a, R1, and R3-6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
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Page/Page column 21

(2010/06/13)

DIARYL KETIMINE DERIVATIVE HAVING ANTAGONISM AGAINST MELANIN-CONCENTRATING HORMONE RECEPTOR
[Problems] To provide an antagonist of a melanin-concentrating hormone receptor, which is useful as a medicine for a central nervous system disease, a cardiovascular disease or a metabolic disease. [Means for Solving Problems] The antagonist comprises, as an active ingredient, a compound represented by the formula (I) wherein R1a and R1b independently represent a hydrogen atom or a C1-6 alkyl group; R2a, R2b, R3a and R3b independently represent a hydrogen atom, a C1-6 alkyl group, or the like; Y represents H or —OH; Z represents —OR8, or the like; R8 represents a hydrogen atom, a C1-6 alkyl group which may have a substituent, or the like; R9a and R9b independently represent a hydrogen atom, a C1-6 alkyl group, or the like; Ar1 represents an aromatic carbon ring group, or an aromatic heteroring group; Ar2 represents a group produced by removing two hydrogen atoms from an aromatic carbon ring, or the like; and the ring group A represents an unsaturated heteroring group.
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Page/Page column 25-26

(2010/12/31)

AMINO PYRIMIDINE ANTICANCER COMPOUNDS
Compounds of Formula (1), as shown below and defined herein: and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancers mediated at least in part by FAK.
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Page/Page column 88

(2010/12/29)

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS
The present invention relates to novel compounds that are CGRP receptor antagonists, processes for their preparation, to compositions containing them and to their use in the treatment of migraine, headache, and cluster headache.
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Page/Page column 56

(2009/07/25)

α-Hydroxyalkyl heterocycles via chiral allylic boronates: Pd-catalyzed borylation leading to a formal enantioselective isomerization of allylic ether and amine
(Chemical Equation Presented) An efficient catalytic enantioselective preparation of synthetically useful pyranyl and piperidinyl allylic boronates was achieved via a palladium-catalyzed borylation/isomerization reaction on the corresponding alkenyl triflates. The influence of the base and solvent was found to be crucial on the regio- and enantioselectivity of this reaction. The overall borylation process constitutes a successful example of formal asymmetric isomerization of allylic ether/amine. The resulting allylic boronate reagents add to various aldehydes in a one-pot process to give synthetically useful alpha-hydroxyalkyl derivatives in high stereoselectivity.
Lessard, Stephanie,Peng, Feng,Hall, Dennis G.
supporting information; experimental part
p. 9612 - 9613
(2011/03/20)

Design, synthesis, and evaluation of novel aryl-tetrahydropyridine PPARα/γ dual agonists
Aryl-tetrahydropyridine derivatives were prepared and their PPARα/γ dual agonistic activities were evaluated. Among them, compound (S)-5b was identified as a potent PPARα/γ dual agonist with an EC50 of 1.73 and 0.64 μM in hPPARα and γ, respectively. In diabetic (db/db) mice, compound (S)-5b showed good glucose lowering efficacy and favorable pharmacokinetic properties.
Kim, Eunkyung,Park, Chan Sun,Han, Taedong,Bae, Myung-Ho,Chong, Wonee,Lee, Choong Hyun,Shin, Young Ah,Ahn, Byung-Nak,Kim, Mi Kyung,Shin, Chang Yell,Son, Moon Ho,Kim, Jin Kwan,Moon, Ho Sang,Shim, Hyun Joo,Kim, Eun Jung,Kim, Soon Hoe,Lim, Joong In,Lee, Chun Ho
scheme or table
p. 4993 - 4996
(2009/05/26)

A novel class of cycloalkano[b]pyridines as potent and orally active opioid receptor-like 1 antagonists with minimal binding affinity to the hERG K + channel
A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl} -6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-9-ol ((-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K+ channel. From these studies, 101 was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K+channel. Furthermore, 101 showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.
Yoshizumi, Takashi,Takahashi, Hirobumi,Miyazoe, Hiroshi,Sugimoto, Yuichi,Tsujita, Tomohiro,Kato, Tetsuya,Ito, Hirokatsu,Kawamoto, Hiroshi,Hirayama, Mioko,Ichikawa, Daisuke,Azuma-Kanoh, Tomoko,Ozaki, Satoshi,Shibata, Yoshihiro,Tani, Takeshi,Chiba, Masato,Ishii, Yasuyuki,Okuda, Shoki,Tadano, Kiyoshi,Fukuroda, Takahiro,Okamoto, Osamu,Ohta, Hisashi
scheme or table
p. 4021 - 4029
(2009/05/26)

KINASE INHIBITOR COMPOUNDS
Pyridine and pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
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Page/Page column 59-60

(2008/12/07)

5-PHENYL-1,3,4-OXADIAZOL-2-YL-ACETYL-4-PIPERIDINYL DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS
The present invention relates to novel compounds that are CGRP receptor antagonists, processes for their preparation, to compositions containing them and to their use in the treatment of migraine, headache, and cluster headache.
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Page/Page column 52

(2009/03/07)

SMALL MOLECULE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASES (PRMTS)
The present invention relates to compounds that are useful as inhibitors of protein arginine methyltransferase that have a formula selected from Formula (I), Formula (II) and Formula (III), as well as racemic mixtures, diastereomers, enantiomers and tautomers thereof and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof as defined herein. Said compound are useful as inhibitors of PRMTs and/or CARM-I. The invention further relates to compositions comprising such compounds and methods for their use.
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Page/Page column 117

(2008/12/08)

DIACYLGLYCEROL ACYLTRANSFERASE INHIBITORS
Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.
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Page/Page column 61

(2009/01/20)

11-BETA HSD1 INHIBITORS
This invention relates to inhibiting 11βHSD1.
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Page/Page column 144-145

(2008/06/13)

SUBSTITUTED 4-AMINO-PYRROLOTRIAZINE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH ANGIOGENESIS
This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds and compositions for the prevention and/or treatment of hyper-proliferative disorders and diseases associated with angiogenesis.
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Page/Page column 362

(2008/06/13)

L-PHENYLALANINE DERIVATIVES
The present invention relates to compounds that inhibit of a5b1 function, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment in warm blooded animals such as humans of diseases that have a significant angiogenesis or vascular component such as for treatment of solid tumours. The present invention also relates to compounds that inhibit a5b1, and also that exhibit appropriate selectivity profile(s) against other integrins.
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(2008/06/13)