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MF C23H14ClF3N4
MW: 438.0859


3-(4-chloro-3- (trifluoromethyl)phenyl)-4-cyclopropyl-6-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile

1H NMR (600 MHz, DMSO-d6) δ = 14.46 (br. s., 1H), 8.24 (s, 1H), 8.14 (d, J=8.1 Hz, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.84 (dd, J=6.1, 2.7 Hz, 2H), 7.61 – 7.55 (m, 3H), 2.50 – 2.45 (m, 1H), 0.74 – 0.68 (m, 2H), 0.65 – 0.59 (m, 2H).

13C NMR (126 MHz, DMSO-d6) δ 160.5, 155.0, 153.0, 144.1, 138.3, 135.4, 133.9, 132.0, 131.2, 130.3, 129.7, 128.9, 128.9, 128.8, 127.0 (q, J=30.5 Hz), 118.1, 112.4, 103.9, 14.6, 9.4.

LCMS (method A) tR, 2.01 min, MS Anal. Calcd. for [M+H]+ C23H15ClF3N4: 439.09; found: 439.15.

LC/MS HPLC methods: method A: Column: Phenomenex Luna 30 x 2.0 mm 3um; Mobile Phase A: 10:90 acetonitrile:water with 0.1% TFA; Mobile Phase B: 90:10 acetonitrile:water with 0.1% TFA; Temperature: 40 °C; Gradient: 0-100% B over 2 min; Flow: 1 mL/min.


Image result for Bristol-Myers Squibbimg

Senior Research Investigator II at Bristol-Myers Squibb

Highly effective leader seeking to apply innovative thinking and critical analysis to strategy and scientific challenges. Diverse educational background, including recent MBA studies, provides foundation for excellent communication, collaboration, and team building across organizational functions. Experience includes 13 years of cutting-edge scientific research in a global work environment, specializing in the fields of organic chemistry and drug discovery.


Senior Research Investigator II

Bristol-Myers Squibb

July 2014 – Present (2 years 4 months)Wallingford, CT

Oncology Discovery Chemistry, Program: Bromodomain and Extra-Terminal Inhibitor Program, undisclosed target



BMT-145027 is a potent mGluR5 PAM with no inherent mGluR5 agonist activity. BMT-145027 is a non-MPEP site PAM to demonstrate in vivo efficacy. BMT-145027 has mGluR5 PAM EC50 = 47 nM, with fold shit = 3.5, and is effective in mouse NOR. The metabotropic glutamate receptor 5 (mGluR5) is an attractive target for the treatment of schizophrenia due to its role in regulating glutamatergic signaling in association with the N-methyl-D-aspartate receptor (NMDAR).

Abstract Image

The metabotropic glutamate receptor 5 (mGluR5) is an attractive target for the treatment of schizophrenia due to its role in regulating glutamatergic signaling in association with the N-methyl-d-aspartate receptor (NMDAR). We describe the synthesis of 1H-pyrazolo[3,4-b]pyridines and their utility as mGluR5 positive allosteric modulators (PAMs) without inherent agonist activity. A facile and convergent synthetic route provided access to a structurally diverse set of analogues that contain neither the aryl-acetylene-aryl nor aryl-methyleneoxy-aryl elements, the predominant structural motifs described in the literature. Binding studies suggest that members of our new chemotype do not engage the receptor at the MPEP and CPPHA mGluR5 allosteric sites. SAR studies culminated in the first non-MPEP site PAM, 1H-pyrazolo[3,4-b]pyridine 31 (BMT-145027), to improve cognition in a preclinical rodent model of learning and memory.

Development of 1H-Pyrazolo[3,4-b]pyridines as Metabotropic Glutamate Receptor 5 Positive Allosteric Modulators

Matthew D. Hill*, Haiquan Fang, Jeffrey M. Brown, Thaddeus Molski, Amy Easton, Xiaojun Han, Regina Miller, Melissa Hill-Drzewi, Lizbeth Gallagher, Michele Matchett, Michael Gulianello, Anand Balakrishnan, Robert L. Bertekap, Kenneth S. Santone, Valerie J. Whiterock, Xiaoliang Zhuo, Joanne J. Bronson, John E. Macor, and Andrew P. Degnan
Research and Development, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, Connecticut 06492-7660, United States
ACS Med. Chem. Lett., Article ASAP
DOI: 10.1021/acsmedchemlett.6b00292,

*Tel: 1-203-677-7102. Fax: 1-203-677-7884. E-mail:

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C23 H15 F3 N4, 404.39
1H-Pyrazolo[3,4-b]pyridine-5-carbonitrile, 4-cyclopropyl-6-phenyl-3-[4-(trifluoromethyl)phenyl]-
A Multicomponent Approach to Highly Substituted 1H-Pyrazolo[3,4-b]pyridines
Synthesis (2016), 48, (14), 2201-2204.

A Multicomponent Approach to Highly Substituted 1H-Pyrazolo[3,4-b]pyridines

Matthew D. Hill*

  • Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492-7660, USA

DOI: 10.1055/s-0035-1562230

Compound 12 (500 mg, 65% yield: 1H NMR (500 MHz, DMSO-d6 δ 14.41 (br. s., 1H, 7.86 – 7.80 (m, 3H, 7.76 (dt, J=7.1, 1.6 Hz, 1H, 7.61 – 7.51 (m, 5H, 2.48 – 2.45 (m, 1H, 0.73 – 0.66 (m, 2H, 0.62 – 0.57 (m, 2H. 13C NMR (400 MHz, DMSO-d6 δ 159.98, 154.67, 152.15, 144.68, 137.75, 135.74, 132.69, 129.87, 129.71, 129.14, 128.99, 128.34, 128.24, 128.21, 117.61, 111.88, 103.05, 14.01, 8.75. IR (film: 3228 (s, 3052 (w, 2228 (m, 1581 (s, 1555 (s, 1503 (w, 1447 (m, 1284 (m cm–1. HRMS (ESI: m/z [M+H]+ calcd for C22H16N4Cl: 371.1058; found: 371.1053.

Compound 13 (103 mg, 28% yield: 1H NMR (500 MHz, DMSO-d6 δ 14.50 (br. s., 1H, 8.03 (d, J=7.9 Hz, 2H, 7.92 – 7.80 (m, 4H, 7.63 – 7.55 (m, 3H, 2.51 (br. s., 1H, 0.65 (d, J=7.6 Hz, 2H, 0.56 (d, J=4.3 Hz, 2H. MS (ESI: m/z = 405.15 [M+H]+.



///////////BMT-145027, glutamat mGluR5 novel object recognition positive allosteric modulator,  schizophrenia



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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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