1H-indazole-3-carboxylic acid [CAS 4498-67-3; InChIKey BHXVYTQDWMQVBI-UHFFFAOYSA-N; Reaxys, S by Asch

Query Query

Results

Date

O OH

1 substances in Re2016-03-08 21h:23m:35s (EST) axys

1. Query N NH

Search as: As drawn

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Reaxys ID 6354 View in Reaxys

1/1 CAS Registry Number: 4498-67-3 Chemical Name: 1H-Indazole-3-carboxylic acid Linear Structure Formula: C7H5N2CO2H Molecular Formula: C8H6N2O2 Molecular Weight: 162.148 Type of Substance: heterocyclic InChI Key: BHXVYTQDWMQVBI-UHFFFAOYSA-N Note:

O OH

N NH

Substance Label (25) Label References 18

Giacomini, Elisa; Buonfiglio, Rosa; Masetti, Matteo; Wang, Yuhong; Tseng, Gea-Ny; Roberti, Marinella; Recanatini, Maurizio; Combinatorial Chemistry and High Throughput Screening; vol. 18; nb. 3; (2015); p. 269 - 280, View in Reaxys

Sheng, Rong; Li, Shan; Lin, Guanyu; Shangguan, Shihao; Gu, Yongchuan; Qiu, Ni; Cao, Ji; He, Qiaojun; Yang, Bo; Hu, Yongzhou; RSC Advances; vol. 5; nb. 100; (2015); p. 81817 - 81830, View in Reaxys

CXXXI

Patent; Samumed, LLC; Hood, John; Kumar KC, Sunil; Wallace, David Mark; Mittapalli, Gopi Kumar; Hofilena, Brian Joseph; Mak, Chi Ching; Bollu, Venkataiah; Eastman, Brian; US2015/266825; (2015); (A1) English, View in Reaxys

Karaluka, Valerija; Lanigan, Rachel M.; Murray, Paul M.; Badland, Matthew; Sheppard, Tom D.; Organic and Biomolecular Chemistry; vol. 13; nb. 44; (2015); p. 10888 - 10894, View in Reaxys

VIII

Patent; Samumed, LLC; HOOD, John; WALLACE, David Mark; KC, Sunil Kumar; EP2464232; (2015); (B1) English, View in Reaxys

Foloppe, Nicolas; Fisher, Lisa M.; Francis, Geraint; Howes, Rob; Kierstan, Peter; Potter, Andrew; Bioorganic and Medicinal Chemistry; vol. 14; nb. 6; (2006); p. 1792 - 1804, View in Reaxys; Swamy, Udutha Kumara; Mohan, H. Rama; Prasad, U. Viplava; Suresh; Kumar, T. Laxmi; Asian Journal of Chemistry; vol. 26; nb. 7; (2014); p. 1921 - 1930, View in Reaxys

Liu, Tao; Nonat, Aline; Beyler, Maryline; Regueiro-Figueroa, Martin; Nchiminono, Katia; Jeannin, Olivier; Camerel, Franck; Debaene, Francois; Cianferani-Sanglier, Sarah; Tripier, Raphael; Platas-Iglesias, Carlos; Charbonniere, Loic J.; Angewandte Chemie - International Edition; vol. 53; nb. 28; (2014); p. 7259 - 7263; Angew. Chem.; vol. 126; nb. 28; (2014); p. 7387 - 7391,5, View in Reaxys

Chen, Qianqian; Tian, Wei; Han, Guangqian; Qi, Jingjing; Zheng, Canhui; Zhou, Youjun; Ding, Lili; Zhao, Juntao; Zhu, Ju; Lv, Jiaguo; Sheng, Chunquan; European Journal of Medicinal Chemistry; vol. 59; (2013); p. 176 - 182, View in Reaxys

Patent; SAMUMED, LLC; HOOD, John; KC, Sunil Kumar; WO2013/40215; (2013); (A1) English, View in Reaxys

Crocetti, Letizia; Schepetkin, Igor A.; Cilibrizzi, Agostino; Graziano, Alessia; Vergelli, Claudia; Giomi, Donatella; Khlebnikov, Andrei I.; Quinn, Mark T.; Giovannoni, Maria Paola; Journal of Medicinal Chemistry; vol. 56; nb. 15; (2013); p. 6259 - 6272, View in Reaxys

Crestey, Francois; Stiebing, Silvia; Legay, Remi; Collot, Valerie; Rault, Sylvain; Tetrahedron; vol. 63; nb. 2; (2007); p. 419 - 428, View in Reaxys; Patent; MYREXIS, INC.; KUMAR, Dange Vijay; SLATTUM, Paul M.; YAGER, Kraig M.; SHENDEROVICH, Mark D.; TANGALLAPALLY, Rajendra; KIM, Se-Ho; WO2012/177782; (2012); (A1) English, View in Reaxys

Schmidt, Andreas; Merkel, Lars; Eisfeld, Wolfgang; European Journal of Organic Chemistry; nb. 10; (2005); p. 2124 - 2130, View in Reaxys; Patent; Brice, Jodie; Cedilote, Miall; Dong, Zhiming; Zhang, Pingsheng; US2012/4412; (2012); (A1) English, View in Reaxys

Lukasik, Pawel M.; Elabar, Sherifa; Lam, Frankie; Shao, Hao; Liu, Xiangrui; Abbas, Abdullah Y.; Wang, Shudong; European Journal of Medicinal Chemistry; vol. 57; (2012); p. 311 - 322, View in Reaxys

Patent; Kuang, Shan-Ming; Zhang, Pingsheng; US2011/172428; (2011); (A1) English, View in Reaxys

31b

Patent; INTERMUNE, INC.; US2009/257979; (2009); (A1) English, View in Reaxys

Patent; MICROBIA, INC.; WO2008/19357; (2008); (A2) English, View in Reaxys

16AP

Patent; SCHERING CORPORATION; WO2008/153858; (2008); (A1) English, View in Reaxys

Crestey, Francois; Collot, Valerie; Stiebing, Silvia; Lohier, Jean-Francois; Santos, Jana Sopkova-de Oliveira; Rault, Sylvain; Tetrahedron Letters; vol. 48; nb. 14; (2007); p. 2457 - 2460, View in Reaxys

Patent; SCHERING CORPORATION; WO2007/70398; (2007); (A1) English, View in Reaxys

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Schmidt, Andreas; Beutler, Ariane; Habeck, Tobias; Mordhorst, Thorsten; Snovydovych, Bohdan; Synthesis; nb. 11; (2006); p. 1882 - 1894, View in Reaxys

Munoz-Ruiz, Pilar; Rubio, Laura; Garcia-Palomero, Esther; Dorronsoro, Isabel; Del Monte-Millan, Maria; Valenzuela, Rita; Usan, Paola; De Austria, Celia; Bartolini, Manuela; Andrisano, Vincenza; Bidon-Chanal, Axel; Orozco, Modesto; Javier Luque; Medina, Miguel; Martinez, Ana; Journal of Medicinal Chemistry; vol. 48; nb. 23; (2005); p. 7223 - 7233, View in Reaxys

Patent; PLEXXIKON, INC.; WO2005/9958; (2005); (A1) English, View in Reaxys

Patent; THRESHOLD PHARMACEUTICALS, INC.; WO2005/120498; (2005); (A2) English, View in Reaxys

Patent; Chemagis Ltd.; EP1484321; (2004); (A1) English, View in Reaxys

Hirokawa, Yoshimi; Fujiwara, Iwao; Suzuki, Kenji; Harada, Hiroshi; Yoshikawa, Takashi; Yoshida, Naoyuki; Kato, Shiro; Journal of Medicinal Chemistry; vol. 46; nb. 5; (2003); p. 702 - 715, View in Reaxys

Patent-Specific Data (9) Location in Patent References Page/Page column

Patent; Samumed, LLC; Hood, John; Wallace, David Mark; Kumar KC, Sunil; US2013/267495; (2013); (A1) English, View in Reaxys; Patent; SUVEN LIFE SCIENCES LIMITED; Nirogi, Ramakrishna; Mohammed, Abdul Rasheed; Yarlagadda, Suresh; Ravella, Srinivasa Rao; Shinde, Anil Karbhari; Kamphampati, Ramasastri; Roayapalley, Praveen Kumar; Jayarajan, Pradeep; Bhyrapuneni, Gopinadh; Patnala, Sriramachandra Murthy; Ravula, Jyothsna; Jasti, Venkateswarlu; US2014/187581; (2014); (A1) English, View in Reaxys Patent; PETER MACCALLUM CANCER INSTITUTE; MARTIN, Roger, Francis; WHITE, Jonathan; LOBACHEVSKY, Pavel; WINKLER, David; SKENE, Colin; MARCUCCIO, Sebastian; WO2011/123890; (2011); (A1) English, View in Reaxys Patent; KYOWA HAKKO KOGYO CO., LTD.; EP1878737; (2008); (A1) English, View in Reaxys Patent; SANOFI-AVENTIS; US2007/155749; (2007); (A1) English, View in Reaxys Patent; Georges, Guy; Goller, Bernhard; Kuenkele, Klaus-Peter; Limberg, Anja; Reiff, Ulrike; Rueger, Petra; Rueth, Matthias; Schuell, Christine; US2006/142247; (2006); (A1) English, View in Reaxys Patent; PFIZER LIMITED; WO2006/123242; (2006); (A1) English, View in Reaxys Patent; SANOFI-AVENTIS; US2005/182062; (2005); (A1) English, View in Reaxys Patent; THRESHOLD PHARMACEUTICALS, INC.; WO2005/120498; (2005); (A2) English, View in Reaxys Patent; Aventis Pharma S.A.; US2005/9894; (2005); (A1) English, View in Reaxys

Purification (1) References Piozzi et al.; Gazzetta Chimica Italiana; vol. 95; (1965); p. 814,817, View in Reaxys Melting Point (12) 1 of 12

Melting Point [°C]

266

Joubert, Jacques; van Dyk, Sandra; Malan, Sarel F.; Bioorganic and Medicinal Chemistry; vol. 16; nb. 19; (2008); p. 8952 - 8958, View in Reaxys 2 of 12

Melting Point [°C]

267 - 268

Solvent (Melting Point)

acetic acid

Ferrari, Marinella; Ripa, Alberto; Ripa, Giorgio; Sisti, Massimo; Journal of Heterocyclic Chemistry; vol. 26; (1989); p. 531 - 532, View in Reaxys 3 of 12

Melting Point [°C]

260 - 262

Piozzi et al.; Gazzetta Chimica Italiana; vol. 95; (1965); p. 814,817, View in Reaxys 4 of 12

Melting Point [°C]

261 - 263

Patent; Badische Anilin- u. Soda-Fabrik AG; FR1425219; (1964); Chem.Abstr.; vol. 65; nb. 13721c; (1966), View in Reaxys 5 of 12

Melting Point [°C]

260

Solvent (Melting Point)

aq. methanol

Patent; Henkel and Cie.; GB816531; (1957); US3023210; (1958); Chem.Abstr.; nb. 1552; (1960), View in Reaxys 6 of 12

Melting Point [°C]

268 - 268.5

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Solvent (Melting Point)

H2O

Snyder et al.; Journal of the American Chemical Society; vol. 74; (1952); p. 2009,2010, View in Reaxys 7 of 12

Melting Point [°C]

260 - 261

v. Auwers; Dereser; Chemische Berichte; vol. 52; (1919); p. 1345,1348, View in Reaxys 8 of 12

Melting Point [°C]

259

Pschorr; Hoppe; Chemische Berichte; vol. 43; (1910); p. 2550, View in Reaxys 9 of 12

Solvent (Melting Point)

ethanol; H2O

Schad; Chemische Berichte; vol. 26; (1893); p. 218, View in Reaxys 10 of 12

Solvent (Melting Point)

acetic acid

Schad; Chemische Berichte; vol. 26; (1893); p. 218, View in Reaxys 11 of 12

Melting Point [°C]

258 - 259

Comment (Melting Point) Decomp. Schad; Chemische Berichte; vol. 26; (1893); p. 218, View in Reaxys 12 of 12

Melting Point [°C]

254

Comment (Melting Point) Decomp.sublimierbar. Salkowski,H.; Chemische Berichte; vol. 17; (1884); p. 506; Chemische Berichte; vol. 22; (1889); p. 2139, View in Reaxys Crystal Property Description (5) Colour & Other Location Properties yellow

Page/Page column 47

References Patent; GLENMARK PHARMACEUTICALS S.A.; DAS, Sanjib; CHAUDHARI, Sachin Sundarlal; THOMAS, Abraham; PARDESHI, Shailesh Ramesh; DESHMUKH, Vishal Govindrao; WADEKAR, Prashant Dilip; KHAIRATKAR-JOSHI, Neelima; SHAH, Daisy Manish; BAJPAI, Malini; WO2015/87234; (2015); (A1) English, View in Reaxys

light-yellow

Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/111038; (2005); (A2) English, View in Reaxys

hellgelb

Snyder et al.; Journal of the American Chemical Society; vol. 74; (1952); p. 2009,2010, View in Reaxys

Nadeln

Schad; Chemische Berichte; vol. 26; (1893); p. 218, View in Reaxys

Tafeln

Schad; Chemische Berichte; vol. 26; (1893); p. 218, View in Reaxys

NMR Spectroscopy (3) 1 of 3

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Frequency (NMR Spectroscopy) [MHz]

300

Original Text (NMR Spectroscopy)

1H NMR (300 MHz, DMSO-i) δ 7.27 (t, = 7.5 Hz, 1H), 7.43 (t, = 7.2 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 12.85 (br s, 1H), 13.79 (br s, 1H).

Location

Page/Page column 47

Patent; GLENMARK PHARMACEUTICALS S.A.; DAS, Sanjib; CHAUDHARI, Sachin Sundarlal; THOMAS, Abraham; PARDESHI, Shailesh Ramesh; DESHMUKH, Vishal Govindrao; WADEKAR, Prashant Dilip; KHAIRATKARJOSHI, Neelima; SHAH, Daisy Manish; BAJPAI, Malini; WO2015/87234; (2015); (A1) English, View in Reaxys 2 of 3

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

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Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Ferrari, Marinella; Ripa, Alberto; Ripa, Giorgio; Sisti, Massimo; Journal of Heterocyclic Chemistry; vol. 26; (1989); p. 531 - 532, View in Reaxys 3 of 3

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

nujol

Comment (IR Spectroscopy)

3200 - 1680 cm**(-1)

Ferrari, Marinella; Ripa, Alberto; Ripa, Giorgio; Sisti, Massimo; Journal of Heterocyclic Chemistry; vol. 26; (1989); p. 531 - 532, View in Reaxys Mass Spectrometry (1) Description (Mass References Spectrometry) spectrum

Ferrari, Marinella; Ripa, Alberto; Ripa, Giorgio; Sisti, Massimo; Journal of Heterocyclic Chemistry; vol. 26; (1989); p. 531 - 532, View in Reaxys

UV/VIS Spectroscopy (1) 1 of 1

Description (UV/VIS Spectroscopy)

Spectrum

Solvent (UV/VIS Spectroscopy)

H2O

Comment (UV/VIS Spectroscopy)

220 - 315 nm

Rousseau; Lindwall; Journal of the American Chemical Society; vol. 72; (1950); p. 3047,3049, View in Reaxys Fluorescence Spectroscopy (1) Description (Fluo- References rescence Spectroscopy) Fluorescence

Joubert, Jacques; van Dyk, Sandra; Malan, Sarel F.; Bioorganic and Medicinal Chemistry; vol. 16; nb. 19; (2008); p. 8952 - 8958, View in Reaxys

Pharmacological Data (6) 1 of 6

Comment (Pharmacological Data)

Bioactivities present

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Effect (Pharmacological Data)

D-amino acid oxidase (DAO); inhibition of

Species or Test-System (Pharmacological Data)

kidney DAO of porcine

Method (Pharmacological Data)

D-AMINO ACID OXIDASE RELATED ASSAYSPorcine kidney D-amino acid oxidase (catalog No. A-5222 from Sigma) and 0-serine (catalog U 8-4250 from Sigma) was used to test the DAO inhibitory activity of test compounds. The breakdown of D-serine by DAO produces hydrogen peroxidase, which can be measured using, for example, the Amplex.(R). Red Hydrogen Peroxide Assay Kit (Catalog No. A-22188, Molecular Probes, Inc.; Eugene, OR), A working solution was prepared by mixing: distilled water (7.93 rat), sodium phosphate buffer (1 ml 0.25M, pi-i 7.4), D-seriise solution (1 ,0 ml, 100 rnM in water), horseradish peroxidase (0.02 mi, I CK) U /ml in buffer), and Amplex Red solution (0,05 mi, 1 mg dye in 200 u\\ in DMSO (50 μM in DMSO)). A working enzyme solution is prepared by diluting a D -amino acid oxidase stock solution (65 U/ml) Four hundred fold. The working solution (99 μl) was transferred u> wells of a Microfiuor mierotiier plate and a solution of the inhibitor in DMSO (1 μL) is added. The working enzyme solution (20μl) was added to each well and the rate of reaction (hydrogen peroxide released) was determined by measuring the oxidation of Ampiex Red by spectrophotometry, using a plate reader (excitation wavelength 544 nm, emission wavelength, 590 nM) after a reaction time of ? 5 minutes. Controls were carried out using DMSO in the absence of inhibitor. A known DAO inhibitor, iκdole-2-carboxylic acid, was used as a control in this assay. Figure 3, Figure 5 and Figure 8 present the results of the analysis of certain compounds in the DAO assay.

Location

Page/Page column 74; 535; 71/99

Comment (Pharmacological Data)

No effect

Patent; MICROBIA, INC.; WO2008/19357; (2008); (A2) English, View in Reaxys 3 of 6

Effect (Pharmacological Data)

D-amino acid oxidase (DAO); inhibition of

Species or Test-System (Pharmacological Data)

DAO derived from HEK293 cells stably transfected with human DAO (huDAO) clone of human

Method (Pharmacological Data)

Inhibition of human DAO53S Human D-araino acid oxidase extracts were prepared by harvesting HEK293 cells either transiently or stably transfected with the human DAO clone (huDAO). The stable huDAO ceil line was generated by co-transiecting the huDAO gene (Catalog/?TC1 18941, Origene, Rockville, MD) akmg with pcDNAS.I (Invitragen, Carlsbad, CA) at a 100:1 ratio into HEK.293 ceils under G41 S selection. Transient huDAO transections were implemented using Lipofectamine 2000 (Invitrogen, Carlsbad, CA) arsd following the manufacturers protocol with the following specifics. HBK293 cells were seeded at 2 x 107 cells per 1150 flask the day before transaction. huDAO DNA (CatalogNo.TCi 18941, Origene. Rockville, MD) was transfected at 37.5 ug per flask and at a 3:1 DNA/Lipofectanne ratio. The DNA/Lipofectamine mixture was iπeuhauxi on the cells for 48 hrs before cell harvesting. Similar results were obtained with transiently vs stably expressed huDAO, Extraets were harvested as follows. Culture liquid was removed from flasks and replaced with Hank's Buffered Saline Solution (20 rnLs), The cells were scraped into the Hank's Buffer and then transferred to a fresh tube. Samples were spun for 10 minutes at S.OQOrpm. The supernatant was decanted and the pellet resuspeaded in 50 mM Tm-HCL pHS.7, 1 μM FAD and 1 mM DTT, 20percent glycerol (1 ml..}. Samples were then homogenized on ice for 20 seconds, Hornogenates were spun down tor 5 minutes at 3,ψrpm. 'The supemataπts were re-

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moved and set. aside. The pellets were resuspended m SGmM Tris-HCL pHS.7, 1 μ.M FAD, I mM DIT and 0. USDpercent octyi-β-D- gueoside, 20percent glycerol (1 ml,) and homogenized on ice for 20 seconds. Homogenates were spun for 5 minutes at 3,000rpm. The supematants were collected and combined with previously collected supematants for a master stoek. Extracts were then serially diluted and tested in the D-amino acid oxidase enzyme assay to determine activity based on protein concentration. Stocks were prepared accordingly, typically, for a twenty fold dilution in future assays.Human D-arnino acid oxidase (HEIC293 ceils stably transfected with huDAO clone) and D-serine (catalog No. S-42S0 from Sigma) were used to test the DAO inhibitory activity of test compounds. The breakdown of D-serine by DAO produces hydrogen peroxidase, which cm be measured using, for example, the Amplex.(C). Red Hydrogen Peroxide Assay Kit (Catalog No. A-22188, Molecular Probes, Inc.; Eugene, OR). A working solution was prepared by mixing: distilled water {7.93 mL), sodium phosphate buffer ( 1 ml 0. 25M, pH 7.4), -scrine solution {1.0 mi, 100 m.M in water), horseradish peroxidase (0.02 in K 100 UAiil in buffer), and Amp lex Red solution (0.05 ml, I Big dye m 200 ul in DMSO (50 μM m DMSO)), A working enzyme solution was typically prepared by diluting a D- arniπo acid oxidase stock solution twenty fold. 'File svrking solution (99 μl) was transferred to wells of a Microfiuor. microliter plate and a solution of the inhibitor inDMSO (1 μL) is added. 'Hie working enzyme solution (2OuI) was added to each well and the rate of reaction {hydrogen peroxide released) was determined by measuring

using a plate reader (excitation wavelength 544 nm. emission wavelength, 590 nM) alter a reaction time of 1 S minutes. Controls were carried out using DMSO in the absence of inhibitor. A known DAO inhibitor, indole- 2-carboxyiic acid, was used as a control in this assay. Figure SB presents the results of the analysis of certain compounds in the DAC) assay. the oxidation of Amp lex Red by spectrophotometry &>

Results

inhibition at 10μM of title compound was 10 - 50percent

Location

Page/Page column 74; 535-537; 71/99

Patent; MICROBIA, INC.; WO2008/19357; (2008); (A2) English, View in Reaxys 4 of 6

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

brain homogenate of Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

Ca. 0.1 - 1000 μmol/l

Kind of Dosing (Pharma- title comp. dissolved in HEPES buffer, methanol, tetrahydrofuran or DMSO cological Data) Further Details (Pharma- IC50 related to: nitric oxide synthase, brain cological Data) Type (Pharmacological Data)

log IC50

Value of Type (Pharmacological Data)

-3.28 mol/l

Joubert, Jacques; van Dyk, Sandra; Malan, Sarel F.; Bioorganic and Medicinal Chemistry; vol. 16; nb. 19; (2008); p. 8952 - 8958, View in Reaxys 5 of 6

Effect (Pharmacological Data)

enzyme activity; inhibition of

Species or Test-System (Pharmacological Data)

brain homogenate of Sprague-Dawley rat

Sex

male

Concentration (Pharmacological Data)

Ca. 0.1 - 1000 μmol/l

Kind of Dosing (Pharma- title comp. dissolved in HEPES buffer, methanol, tetrahydrofuran or DMSO cological Data) Results

molecular target: nitric oxide synthase

Joubert, Jacques; van Dyk, Sandra; Malan, Sarel F.; Bioorganic and Medicinal Chemistry; vol. 16; nb. 19; (2008); p. 8952 - 8958, View in Reaxys 6 of 6

Effect (Pharmacological Data)

antibacterial

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Species or Test-System (Pharmacological Data)

Gram-positive and Gram-negative bacteria

Concentration (Pharmacological Data)

400 μg/disc

Method (Pharmacological Data)

disc-diffusion method according to the National Committee for Clinical Laboratory Standards approved standard M7-A; Mueller-Hinton agar medium; sterile filter discs were soaked in title comp. solution; 24 h incubation at 35 deg C

Comment (Pharmacological Data)

No effect

StefanI ska; Gralewska; StarosI ciak; Kazimierczuk, Zygmunt; Pharmazie; vol. 54; nb. 12; (1999); p. 879 - 884, View in Reaxys

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