Reference_01_08_2014_165529

14. Cyanomethylpyrazolecarboxamides as janus kinase inhibitors and their preparation

By Brubaker, Jason; Childers, Matthew Lloyd; Christopher, Matthew; Close, Joshua T.; Katz, Jason David; Jung, Joon; Peterson, Scott; Siliphaivanh, Phieng; Siu, Tony; Smith, Graham Frank; et al

From PCT Int. Appl. (2013), WO 2013043962 A1 20130328, Language: English, Database: CAPLUS

The invention provides compds. of formula I which are JAK inhibitors, and as such are useful for the treatment of JAKmediated diseases such as rheumatoid arthritis, asthma, COPD and cancer. Compds. of formula I wherein Ra and R4 are independently H and C1-4 alkyl; A is aryl and heteroaryl; n is 0, 1, 2, 3, and 4; E is (CH2)0-3; each X is independently C, N, O and S; R3 and R7 are independently H, halo, C1-10 alkyl, C2-10 alkenyl, etc.; R5a is halo, heteroarylsulfonyl, C1-10 alkylsulfonyl, amino, CN, etc.; and pharmaceutically acceptable salts and stereoisomers thereof, are claimed. Example compd. II was prepd. by conjugate addn. of 5-amino-1H-pyrazole-4-carboxylic acid Me ester to tert-Bu 4- (cyanomethylidene)piperidine-1-carboxylate; the resulting tert-Bu 4-[3-amino-4-(methoxycarbonyl)-1H-pyrazol-1-yl]-4- (cyanomethyl)piperidine-1--carboxylate underwent arylation with bromobenzene to give tert-Bu 4-(cyanomethyl)-4-[4- (methoxycarbonyl)-3-(phenylamino)-1H-pyrazol-l-yl]piperidine-1-carboxylate, which underwent hydrolysis to give 1-[1- (tert-butoxycarbonyl)-4-(cyanomethyl)piperidin-4-yl]-3-(phenylamino)-1H-pyrazole-4-carboxylic acid, which underwent amidation with methylamine to give compd. II. The invention compds. were evaluated for their JAK inhibitory activity (data given).

~1 Citing

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

15. Pyrazolecarboxamides as janus kinase inhibitors and their preparation

By Brubaker, Jason; Close, Joshua; Siu, Tony; Smith, Graham Frank; Torres, Luis E.; Woo, Hyun Chong; Young, Jonathan R.; Wei, Zhongyong; Shi, Feng

From PCT Int. Appl. (2013), WO 2013041042 A1 20130328, Language: English, Database: CAPLUS

The invention provides compds. of formula I which are JAK inhibitors, and as such are useful for the treatment of JAKmediated diseases such as rheumatoid arthritis, asthma, COPD and cancer. Compds. of formula I wherein Ra and R4 are independently H and C1-4 alkyl; A is aryl and heteroaryl; n is 0, 1, 2, 3, and 4; E is Xn; n is 2, 3 and 4; X is independently C, N, O and S, provided that at least one X is C; R2 and R3 are independently H, halo, C1-10 alkyl, C2-10 alkenyl, etc.; R5a is H, halo, C1-10 alkylsulfonyl, amino, CN, etc.; and pharmaceutically acceptable salts and stereoisomers thereof, are claimed. Example compd. II was prepd. conjugate addn. of 3-(phenylamino)-1H-pyrazole-4- carboxamide to tert-Bu 5-cyano-3,6-dihydropyridine-1(2H)-carboxylate followed by sepn. of diastereoisomers. The invention compds. were evaluated for their JAK inhibitory activity (data given).

~1 Citing

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

16. Preparation of pyrazole compounds as SGLT1 inhibitors

By Miura, Tomoya; Ogoshi, Yosuke; Ueyama, Kazuhito; Motoda, Dai; Iwayama, Toshihiko; Suzawa, Koichi; Nagamori, Hironobu; Ueno, Hiroshi; Takahashi, Akihiko; Sugimoto, Kazuyuki

From PCT Int. Appl. (2013), WO 2013031922 A1 20130307, Language: Japanese, Database: CAPLUS

Title compds. I [ring Cy = aryl, cycloalkyl or cycloalkenyl; n1 = 0-4; R1a = halo, hydroxy, carboxy, etc.; R2a = alkyl, cycloroalkyl-alkyl, aryl-alkyl, etc.; ring Cya = Q1, etc.; p = 1 or 2; q = 1 or 2; n2 = 0-4; R3a = hydroxy, alkyl or hydroxyalkyl; or pharmaceutically acceptable salts thereof], useful for the treatment of type II diabetes, were prepd. For example, oxidn. of 1-phenyl-4,5-dihydro-1H-pyrazol-3-ylamine, reaction with 2,5-hexanedione, iodination, treatment with hydroxylamine·HCl, Pd(OAc)2-catalyzed coupling reaction with 3- (trifluoromethoxy)phenylboronic acid, and WSC·HCl-mediated acylation with (3R,4R)-4-methyl-5-oxopyrrolidine-3-carboxylic acid afforded compd. II. In SGLT1 inhibition assay, IC50 of II was 0.004 μM. Pharmaceutical compns. comprising II are disclosed.

~0 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

17. Preparation of phenylpyrimidinylcarboxylic acid derivatives and analogs for use as kynurenine-3-monooxygenase inhibitors

By Courtney, Stephen Martin; Prime, Michael; Mitchell, William; Brown, Christopher John; De Aguiar Pena, Paula C.; Johnson, Peter; Dominguez, Celia; Toledo-Sherman, Leticia M.; Munoz, Ignacio

From PCT Int. Appl. (2013), WO 2013033085 A1 20130307, Language: English, Database: CAPLUS

Title compds. I [L = C(O), C(O)O, S(O)2NH, etc.; X and Y independently = N or CH, provided at least one is N; R1 = (un)substituted aryl, monocyclic heteroaryl, 1,3-benzoxazol-5-yl, isoindolin-5-yl, etc.; R2 = H or (un)substituted alkyl; R3 = H, halo, OH, (un)substituted alkyl, etc.; or R1 and R3 taken together to form an (un)substituted bicyclic ring; R5 = H, (un)substituted alkyl, aryl, heteroaryl, etc.; or R3 and R5 taken together to form an (un)substituted ring], and their pharmaceutically acceptable salts, are prepd. and disclosed as kynurenine-3-monooxygenase inhibitors. Thus, e.g., II was prepd. by coupling of 4-chloro-3-nitro-benzene boronic acid and 4,6-dichloropyrimidine followed by carbonylation. Select I were evaluated in inhibition assays, e.g., II demonstrated 101.01% inhibition at 10 μM.

~0 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

18. Preparation of phenyl-3-azabicyclo[3.1.0]hex-3-yl-methanones as GlyT1 inhibitors

By Giovannini, Riccardo; Bertani, Barbara; Ferrara, Marco; Lingard, Iain; Mazzaferro, Rocco; Rosenbrock, Holger From PCT Int. Appl. (2013), WO 2013017657 A1 20130207, Language: English, Database: CAPLUS

~1 Citing

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

19. Preparation of substituted (3-phenyl-4,4,4-trifluorobut-1-en-1-yl)benzene compounds useful in pesticidal compositions

By Hunter, James E.; Lo, William C.; Watson, Gerald B.; Patny, Akshay; Gustafson, Gary D.; Pernich, Dan; Brewster, William K.; Camper, Debra L.; Lorsbach, Beth; Loso, Michael R.; et al

From PCT Int. Appl. (2012), WO 2012177813 A1 20121227, Language: English, Database: CAPLUS

The title compds. I [R1-R5 = H, F, Cl, CN, etc.; R6 = haloalkyl; R7 = H, F, Cl, OH, etc.; R8 = H, alkyl, haloalkyl, etc.; R10 = H, F, Cl, CN, etc.; R11 = (un)substituted alkyl, CO2H, C(O)Oalkyl, etc.; X1 = N, CR12; X2 = N, CR9, CR13; X3 = N, CR9 (wherein R9 = H, F, Cl, alkyl, etc.; R12, R13 = H, F, Cl, CN, etc.)], useful as pesticides, were prepd. Thus, reacting (E)-4-[3-(3,5- dichlorophenyl)-4,4,4-trifluorobut-1-enyl]-2-methylbenzoic acid (prepn. given) with 2,2,2-trifluoroethylamine afforded 50% II. Exemplified compds. I were tested in bioassays on beet armyworm and corn earworm (data given). Compns. comprising I were disclosed.

~0 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

20. Preparation of pyridin-2-amides useful as CB2 agonists

By Bissantz, Caterina; Grether, Uwe; Hebeisen, Paul; Kimbara, Atsushi; Liu, Qingping; Nettekoven, Matthias; Prunotto, Marco; Roever, Stephan; Rogers-Evans, Mark; Schulz-Gasch, Tanja; et al

From PCT Int. Appl. (2012), WO 2012168350 A1 20121213, Language: English, Database: CAPLUS

The invention relates to the prepn. of pyridin-2-amides of formula I and pharmaceutically acceptable salts and esters thereof as CB2 agonists. Compd. of formula I wherein R1 is cycloalkyl, haloalkoxy, pyridinylalkoxy, etc.; R2 is H, halo, (halo)alkyl, alkylsulfonyl, etc.; R3 and R4 together with N form piperidinyl, thiomorpholinyl, 1-hydroxyalkylpyrrolidinyl, etc., and pharmaceutically acceptable salts and esters thereof, are claimed. Example compd. II was prepd. by amination of 5- bromo-6-(cyclopropylmethoxy)pyridine-2-carboxylic acid with pyrrolidine; the resulting 6-cyclopropylmethoxy-5-pyrrolidin-1- ylpyridine-2-carboxylic acid underwent amidation with (2S)-2- amino-4-methyl-1-pentanol. All the invention compds. were evaluated for their CB2 agonistic activity. From the assay it was detd. that example compd. II exhibited EC50 values of 0.003 μM and >10 μM towards CB2 and CB1, resp.

~0 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

21. Preparation of cyclohexyloxy piperidinyl compounds as modulators of the GPR119 receptor and the treatment of disorders related thereto

By Jones, Robert M.; Buzard, Daniel J.; Han, Sangdon; Kim, Sun Hee; Lehmann, Juerg

From PCT Int. Appl. (2012), WO 2012170702 A1 20121213, Language: English, Database: CAPLUS

The present invention relates to compds. of Formula I (wherein R1 is C(O)OR6, C(O)R6, C(S)-OR6, CH2R6, or (un)substituted heteroaryl; R6 is C1-6 alkyl, etc.; R2, R3, R4, and R5 are independently H, C1-C14-alkoxy, (un)substituted C1-C4-alkyl, etc.; or R2 and R3 together form part of an (un)substituted heteroaryl),and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof. I are useful as single pharmaceutical agents or in combination with one or more addnl. pharmaceutical agents, such as, an inhibitor of DPP-IV, a biguanide, an alpha-glucosidase inhibitor, an insulin analog, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analog, in the treatment of, for example, a disorder selected from: a GPR119- receptor-related disorder; a condition ameliorated by increasing secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurol. disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto. Synthetic procedures for prepg. I are exemplified. Example compd. II was prepd. in a 3-step synthesis that culminated in reaction of

(S)-1,1,1-trifluoropropan-2-ol and 4-[(1r,4r)-4-(piperidin-4- yloxy)cyclohexyloxy]nicotinonitrile. In various assays, II was found to be a GPR119 agonist and lowered blood glucose in male 129SVE mice after challenge with glucose.

~0 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

22. Helical twisting power of three-ring chiral molecules and polymerization in cholesteric electrolyte solutions

By Hayashi, Hitoshi; Wang, Aohan; Kawabata, Kohsuke; Goto, Hiromasa

From Materials Chemistry and Physics (2013), 137(3), 816-824. Language: English, Database: CAPLUS, DOI:10.1016/j.matchemphys.2012.10.017

A series of chiral three-ring type compds. with rigid shape was employed as chiral inducers for induction of chiral cholesteric liq. crystal (cholesteric LC) from achiral nematic LC. Helical twisting power of the chiral compds. was estd. with the Cano wedge method. Cholesteric LC electrolyte soln. was prepd. by adding the chiral compds. Subsequently, polymn. in the cholesteric LC was carried out to produce chiroptically active polymer films. This method is different from conventional methods for synthesizing chiral polymers because neither chiral monomers nor asym. catalysts are employed. Surface structure and optical properties of the polymer thus prepd. were examd.

~0 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

23. Preparation of novel spiropiperidine derivatives promoting insulin secretion

By Morimoto, Toshiharu; Koshizawa, Tomoaki; Watanabe, Gen; Fukuda, Tomoaki; Ohgiya, Tadaaki; Yamasaki, Nao; Inoue, Noriyuki; Araki, Takaaki; Tsukagoshi, Hitomi; Hagita, Sumihiko

From PCT Int. Appl. (2012), WO 2012161119 A1 20121129, Language: Japanese, Database: CAPLUS