Modulation of morphology and efficacy of new CB1 receptor antagonist using simple and benign polymeric additives
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Title |
Modulation of morphology and efficacy of new CB1 receptor antagonist using simple and benign polymeric additives
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Creator |
Banerjee, Kaushik
Patel, Darshit R Kulshrestha, Anchal Joshipura, Dhawal Joharapurkar, Amit Ghoshdastidar, Krishnarup Jain, Mukul R Srivastava, Brijesh Kumar Chakraborty, Mukut Pattanayak, Sutanuka Ballabh, Amar |
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Subject |
Obesity
CB1 antagonist crystallography morphology in vivo efficacy |
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Description |
1014-1021
The compound 1, [(1H-[1]benzoxepino[5,4-c]pyrazole-3-carboxamide, 8-chloro-1-(2,4-dichlorophenyl)-4,5-dihydro-N- 1-piperidinyl], a known CB1 modulator has been synthesized and characterized by IR, NMR and single Crystal X-ray study. The single crystal study of 1 displays a number of halogen bonds leading to 1-D network along with other weak noncovalent interactions. The CB1 modulator 1 inherently possesses extremely low solubility in water, which makes its application as drug difficult, and this may be attributed to multiple halogen bonds present in the crystal structure. A series of polymer additives, which are Generally Regarded As Safe (GRAS), have been explored to investigate whether they can modulate the halogen bond present in 1 through formation of various non-bonded interactions. Surprisingly, these polymers are found to change crystal morphology, crystal packing while retaining efficacy and bioavailability. The polymer molecular weight is found to play a significant role in crystal morphology modification especially in case of polyethylene glycol (PEG). The formation of new polymorphic forms of 1 and modification of halogen bond has been established using powder X-ray diffraction and IR study, respectively, in case of PEG 4000, PVPK-30, PVA polymers and compound 1 adducts. |
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Date |
2021-09-29T07:14:03Z
2021-09-29T07:14:03Z 2021-07 |
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Type |
Article
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Identifier |
0975-0983(Online); 0376-4699(Print)
http://nopr.niscair.res.in/handle/123456789/58176 |
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Language |
en
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Publisher |
NIScPR-CSIR, India
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Source |
IJC-B Vol.60B(07) [July 2021]
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