Cadrofloxacin Structure

Cadrofloxacin , CS 940

3-Quinolinecarboxylic acid, 1-cyclopropyl-8-(difluoromethoxy)-6-fluoro-1,4-dihydro-7-[(3S)-3-methyl-1-piperazinyl]-4-oxo-, hydrochloride (1:1)

UNII-1YOQ7J9ACY; 153808-85-6; CADROFLOXACIN HYDROCHLORIDE; 1-cyclopropyl-8-(difluoromethoxy)-6-fluoro-7-[(3s)-3-methylpiperazin-1-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid;

1-cyclopropyl-8-(difluoromethoxy)-6-fluoro-7-[(3S)-3-methylpiperazin-1-yl]-4-oxoquinoline-3-carboxylic acid

Molecular Formula:	C₁₉H₂₀F₃N₃O₄
Molecular Weight:	411.37501 g/mol

Company：HengRui (Originator), Daiichi Sankyo (Originator), UBE (Originator)

A quinolone antibiotic potentially for the treatment of bacterial infections.

Research Code CS-940

CAS No. 153808-85-6(FREE)

Cas 128427-55-4(Cadrofloxacin HCl)

HYDROCHLORIDE

Molecular Weight	447.84
Formula	C19H20F3N3O4 • HCl

OriginatorSankyo; Ube Industries
DeveloperSankyo
ClassAntibacterials; Quinolones; Small molecules
Mechanism of ActionType II DNA topoisomerase inhibitors
- 20 Jun 1996An animal study has been added to the Bacterial infections pharmacodynamics section
- 24 Mar 1995Phase-II clinical trials for Bacterial infections in Japan (PO)

Cadrofloxacin hydrochloride was studied for the treatment of bacterial infections.The compound was originally developed by UBE and Daiichi Sankyo. However, this study was discontinued. The compound currently was developed by Hengrui.

SYNTHESIS

Decarboxylation of 3,5,6-trifluoro-4- hydroxyphthalic acid (I) upon heating at 140 C in an autoclave furnished 2,4,5-trifluoro-3-hydroxybenzoic acid (II). This was converted to ethyl ester (III) by refluxing in EtOH in the presence of H2SO4. Condensation of (III) with chlorodifluoromethane and NaH in hot DMF produced the corresponding difluoromethyl ether, and subsequent basic hydrolysis of the ethyl ester yielded 3- (difluoromethoxy) -2, 4,5-trifluorobenzoic acid (IV). Alternatively, acid (II) was converted to acid chloride with SOCl2 and subsequently condensed with ammonia to give amide (V). After formation of the difluoromethyl ether (VI) under similar conditions as above, acid (IV) was obtained by diazotization of the amide function of (VI) in hot sulfuric acid. The difluoromethoxy acid (IV) was also prepared by direct alkylation of hydroxy acid (II) with chlorodifluoromethane in the presence of NaOH in hot DMF. acid (IV) was activated as the corresponding acid chloride (VII) with SOCl2. Condensation of acid chloride (VII) with the magnesium salt of diethyl malonate gave rise to the benzoylmalonate (VIII). Further decarbethoxylation of (VIII) by heating in the presence of p-toluenesulfonic acid yielded keto ester (IX). This was condensed with triethyl orthoformate in the presence of Ac2O to give the ethoxyacrylate (X), which was converted to enamine (XII) by treatment with cyclopropylamine (XI). The target quinolone system (XIII) was then obtained by intramolecular cyclization of (XII) in the presence of NaH. Then, ethyl ester (XII) cleavage using boron trifluoride etherate provided the key quinolonecarboxylic acid boron chelate (XIV)

Route

US5073556A / US5348961A.

1 to 8 of 8

Patent ID	Date	Patent Title
US2011159049	2011-06-30	PHARMACEUTICAL COMPOSITION
US2010330165	2010-12-30	USE OF CHEMOTHERAPEUTIC AGENTS
US2007196504	2007-08-23	PHARMACEUTICAL COMPOSITION
US2007197501	2007-08-23	Use Of Chemotherapeutic Agents
US2007148235	2007-06-28	PHARMACEUTICAL COMPOSITION
US2005152975	2005-07-14	Pharmaceutical composition
US2004022848	2004-02-05	Medicinal composition
US2003045544	2003-03-06	Use of chemotherapeutic agents

//////CS 940, Quinolone antibiotic , CADROFLOXACIN, NDA

CC1CN(CCN1)C2=C(C=C3C(=C2OC(F)F)N(C=C(C3=O)C(=O)O)C4CC4)F

PLECANATIDE; UNII-7IK8Z952OK; (3-Glutamic acid(D>E))human uroguanylin (UGN); 467426-54-6;

Molecular Formula:	C₆₅H₁₀₄N₁₈O₂₆S₄
Molecular Weight:	1681.88626 g/mol

IUPAC Condensed

H-Asn-Asp-Glu-Cys(1)-Glu-Leu-Cys(2)-Val-Asn-Val-Ala-Cys(1)-Thr-Gly-Cys(2)-Leu-OH

(2S)-2-[[(1R,4S,7S,10S,13S,16R,21R,27S,34R,37S,40S)-10-(2-amino-2-oxoethyl)-34-[[(2S)-4-carboxy-2-[[(2S)-3-carboxy-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]propanoyl]amino]butanoyl]amino]-37-(2-carboxyethyl)-27-[(1R)-1-hydroxyethyl]-4-methyl-40-(2-methylpropyl)-3,6,9,12,15,23,26,29,35,38,41-undecaoxo-7,13-di(propan-2-yl)-18,19,31,32-tetrathia-2,5,8,11,14,22,25,28,36,39,42-undecazabicyclo[14.13.13]dotetracontane-21-carbonyl]amino]-4-methylpentanoic acid

L-Leucine, L-asparaginyl-L-alpha-aspartyl-L-alpha-glutamyl-L-cysteinyl-L-alpha-glutamyl-L-leucyl-L- cysteinyl-L-valyl-L-asparaginyl-L-valyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-, cyclic (4->12),(7->15)-bis(disulfide)

L-Asparaginyl-L-α-aspartyl-N-{(1R,4S,7S,10S,13S,16R,19S,22S,25R,32S,38R)-10-(2-amino-2-oxoethyl)-22-(2-carboxyethyl)-38-{[(1S)-1-carboxy-3-methylbutyl]carbamoyl}-32-[(1R)-1-hydroxyethyl]-19-isobut yl-7,13-diisopropyl-4-methyl-3,6,9,12,15,18,21,24,30,33,36-undecaoxo-27,28,40,41-tetrathia-2,5,8,11,14,17,20,23,31,34,37-undecaazabicyclo[14.13.13]dotetracont-25-yl}-L-α-glutamine

Plecanatide
RN: 467426-54-6

read more at

Plecanatide 普卡那肽 ليكاناتيد плеканатид

naloxegol

Morphinan-3,14-diol, 4,5-epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)-17-(2-
propen-1-yl)-, (5α,6α)-

2. 4,5α-epoxy-6α-[(3,6,9,12,15,18,21-heptaoxadocosan-1-yl)oxy]-17-(prop-2-en-1-
yl)morphinan-3,14-diol

http://www.ama-assn.org/resources/doc/usan/naloxegol.pdf

MOLECULAR FORMULA C34H53NO11

MOLECULAR WEIGHT 651.8

SPONSOR AstraZeneca

CODE DESIGNATION NKTR-118

CAS REGISTRY NUMBER 854601-70-0
The US Food and Drug Administration (FDA) has accepted AstraZeneca’s new drug application (NDA) for naloxegol, an investigational peripherally acting mu-opioid receptor antagonist (PAMORA) for the treatment of opioid-induced constipation (OIC).

read at

FDA accepts AstraZeneca’s new drug application for constipation drug

Naloxegol (INN; NKTR-118), or PEGylated naloxol,^[1] is a peripherally–selective opioid antagonist under development by AstraZeneca, licensed from Nektar, for the treatment of opioid-induced constipation.^[2]

Roland Seifert; Thomas Wieland; Raimund Mannhold; Hugo Kubinyi, Gerd Folkers (17 July 2006). G Protein-Coupled Receptors as Drug Targets: Analysis of Activation and Constitutive Activity. John Wiley & Sons. p. 227. ISBN 978-3-527-60695-5. Retrieved 14 May 2012.
“Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119”. Retrieved 2012-05-14

NALOXEGOL OXALATE

credit kegg

NALOXEGOL OXALATE

http://www.ama-assn.org/resources/doc/usan/naloxegol-oxalate.pdf

Morphinan-3,14-diol, 4,5-epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)-
17-(2-propen-1-yl)-, (5α,6α)-, ethanedioate (1:1)

2. 4,5α-epoxy-6α-[(3,6,7,12,15,18,21-heptaoxadocosyl)oxy]-17-(prop-2-
enyl)morphinan-3,14-diol hydrogen ethanedioate

MOLECULAR FORMULA C34H53NO11 . C2H2O4
MOLECULAR WEIGHT 741.8

SPONSOR AstraZeneca
CODE DESIGNATIONS NKTR-118 oxalate, AZ13337019 oxalate
CAS REGISTRY NUMBER 1354744-91-4

About Opioid-Induced Constipation
Opioids are commonly prescribed to patients experiencing chronic pain, which can provide relief from serious medical conditions including osteoarthritis, cancer, and chronic back pain.¹ There are about 250 million opioid prescriptions written annually in the US alone to treat these conditions.² Patients taking opioids to treat chronic pain commonly experience a side effect known as opioid-induced constipation, which may include infrequent bowel movements and difficulty passing stools or emptying bowels.^1,3 Clinically, OIC is the most prevalent side effect of opioid therapy.⁴ For those patients who take opiates for long term pain management, approximately 40-50 percent commonly experience OIC.⁵ Only about 40-50 percent of those patients experience effective relief from current treatment options.^6,7

About Naloxegol (NKTR-118)
Naloxegol (NKTR-118) is an investigational drug candidate in Phase 3 studies being developed as a once-daily oral tablet for the treatment of opioid-induced constipation. Naloxegol (NKTR-118) was designed using Nektar’s proprietary small molecule polymer conjugate technology. Results of the Phase 2 study of naloxegol (NKTR-118) were presented in October 2009 at the American College of Gastroenterology Annual Clinical Meeting and the American Academy of Pain Management. NKTR-119 is an early stage drug development program that is intended to combine oral naloxegol (NKTR-118) with selected opioids, with the goal of treating pain without the side effect of constipation traditionally associated with opioid therapy.

Nektar and AstraZeneca have a global agreement for both naloxegol (NKTR-118) and NKTR-119. Under the agreement, AstraZeneca has responsibility for the development, global manufacturing and marketing of both naloxegol (NKTR-118) and NKTR-119. For naloxegol (NKTR-118), Nektar is eligible to receive up to $235 million in aggregate payments upon the achievement of certain regulatory milestones, as well as additional tiered sales milestone payments of up to $375 million if the product achieves considerable levels of commercial success. Nektar will also be eligible to receive significant double-digit royalty payments on net sales of naloxegol (NKTR-118) worldwide. For NKTR-119, Nektar would receive development milestone payments as well as tiered sales milestone payments. Nektar will also receive significant double-digit royalty payments on NKTR-119 net sales worldwide.

The AstraZeneca Phase 3 KODIAC Program for Naloxegol (NKTR-118)
The KODIAC Program consists of two randomized, placebo controlled Phase III efficacy studies and an open-label, randomized, placebo-controlled long term safety study. The two efficacy studies are identical with 12-week treatment periods. These studies are intended to evaluate the efficacy, safety and tolerability of an AstraZeneca investigational drug in patients with OIC. KODIAC is part of the KODIAC program of studies looking to determine whether naloxegol (NKTR-118) is safe and effective for the treatment of constipation seen as a side effect in people taking prescription opioid pain medications. AstraZeneca plans the first regulatory filings based on the program in 2013.

References

¹Reimer, K et al. Meeting the challenges of opioid-induced constipation in chronic pain management – a novel approach. Pharmacology. 2009; 83:10-17.

²IMS MAT. December 2010.

³Johanson, JF and Kraltein, J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther. 2007; 25:599-608.

⁴Fakata, K. Peripheral Opioid Antagonists: A Therapeutic Advance for Optimizing Opioid Gastrointestinal Tolerability. The Journal of Family Practice. 2007;56:S1-S12.

⁵Thomas, J. Opioid-Induced Bowel Dysfunction. Journal of Pain and Symptom Management. 2008;35(1):103-113.

⁶Bell, T et al. OBD symptoms impair quality of life and daily activities, regardless of frequency and duration of opioid treatment: results of a U.S. patient survey (PROBE survey). Poster presented at The 25th Annual Scientific Meeting of the American Pain Society. San Antonia, TX, USA.

⁷Pappagallo, M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001:182;S11-S18.

http://newdrugapprovals.wordpress.com/2013/09/28/ema-accepts-astrazenecas-naloxegol-application/

ViiV Healthcare, a joint venture involving GlaxoSmithKline (GSK), Pfizer and Shionogi, has submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for its investigational single-tablet regimen (STR) combining dolutegravir, abacavir and lamivudine for treatment of HIV-1 patients.

click hereViiV Healthcare files new drug application for three-drug HIV pill with US FDA