150378-17-9 Usage
Description
Crixivan was launched in Australia, Switzerland, the UK and the US
as an orally-bioavailable HIV-1 protease inhibitor. The compound can be prepared by
coupling an optically active piperazine derivative with an epoxide derivative (now
commercially available). The synthesis of the proteins, reverse transcriptase,
integrase, structural proteins and a protease, required by the virus to complete its
lifecycle, can be interupted if the protease enzyme is not capable of cleaving a proform
polypeptide chain into these components. lndinavir inhibits this process and is
more potent than the first approved protease inhibitor saquinavir. This effect was
noted by the increase in CD4+ cells and a decrease in HIV RNA levels. Since
indinavir is metabolized by the CYP3A4 isozyme, care must be taken with patients
with hepatic insufficiency and to sex-related differences in the level of this enzyme.
Other than nephrolithiasis (5%), indinavir is relatively safe and well tolerated.
Originator
Merck (USA)
Uses
Different sources of media describe the Uses of 150378-17-9 differently. You can refer to the following data:
1. Indinavir is a member of the novel hydroxyaminopentane amide class of HIV-1 protease inhibitors. Indinavir is used as an antiviral. It is a COVID19-related research product.
2. Indinavir is a member of the novel hydroxyaminopentane amide class of HIV-1 protease inhibitors. Indinavir is used as an antiviral.
Indications
Indinavir (Crixivan) is a potent inhibitor of HIV reverse
transcriptase. It produces the side effects common
to all protease inhibitors and also may produce
nephrolithiasis, urolithiasis, and possibly renal insufficiency
or renal failure. This problem occurs more frequently
in children (approximately 30%) than adults
(approximately 10%) and can be minimized by drinking
at least 1.5 L of water daily. Additional side effects include
asymptomatic hyperbilirubinemia, alopecia, ingrown
toenails, and paronychia. Hemolytic anemia
rarely occurs. Rifampin should not be given with indinavir.
Brand name
Crixivan
Acquired resistance
The major mutations in the protease enzyme associated with
loss of the antiretroviral activity occur at positions 46, 82 and
84. Generally, the level of resistance rises with the number of
point mutations.
General Description
When administered with a high-fat diet, indinavir(Crixivan) achieves a maximum serum concentration of77% of the administered dose. The drug is 60% bound inthe plasma. It is extensively metabolized by CYP3A4, andseven metabolites have been identified. Oral bioavailabilityis good, with a tmax of 0.8±0.3 hour. The half-life ofelimination is 1.8 hour, and the elimination products aredetectable in feces and urine. Indinavir also causes dyslipidemia.The available dosage forms are capsules of 200 mg,333 mg, and 400 mg.
Pharmaceutical Applications
A synthetic compound formulated as the sulfate for oral
administration.
Pharmacokinetics
Oral absorption: c. 65%v
Cmax 800 mg thrice daily: c. 8.97 mg/L
Cmin 800 mg thrice daily: c. 0.15 mg/L
Plasma half-life: c. 2 h
Volume of distribution: c. 0.4–1.74 L/kg
Plasma protein binding: c. 60%
Absorption and distribution
It is rapidly absorbed and not significantly affected by intake with food. Distribution in the body has not been fully characterized. It penetrates well into the CNS. The semen:plasma ratio is 1.9. It is distributed into breast milk.
Metabolism and excretion
Seven major metabolites have been described, including a glucuronide conjugate and six oxidative metabolites. Around 83% of the dose is recovered in feces and 18% in urine, 10% as unchanged drug. The effect of renal impairment has not been studied. It should be used with caution in the presence of hepatic impairment, particularly if severe.
Clinical Use
Treatment of adult HIV infection (in combination with other antiretroviral
drugs)
Side effects
The principal side effect is nephrolithiasis, including flank pain
with or without hematuria. There is good evidence that indinavir
directly causes nephrolithiasis as a result of crystallization
in the urinary tract. Indirect hyperbilirubinemia occurs in
about 10% of patients associated with inhibition of bilirubinconjugating
activity occurring as a result of competitive inhibition
of uridine diphosphate (UDP)-glucuronosyltransferase.
Ritonavir-boosted indinavir is associated with a dyslipidemia
profile characteristic of those treated with other
protease
inhibitors boosted with a 200 mg dose of ritonavir
per day. Insulin resistance and hyperglycemia have also been
associated with ritonavir-boosted indinavir.
Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: possibly increased amiodarone
and flecainide concentration - avoid.
Antibacterials: rifampicin increases metabolism
- avoid concomitant use; increased rifabutin
concentration - avoid; avoid with telithromycin in
severe renal and hepatic failure.
Anticoagulants: avoid with apixaban and
rivaroxaban.
Antidepressants: concentration reduced by St John’s
wort - avoid.
Antiepileptics: concentration possibly reduced
by carbamazepine, fosphenytoin, phenytoin,
primidone and phenobarbital, also concentration
of carbamazepine, fosphenytoin and phenytoin
increased.
Antifungals: itraconazole and ketoconazole inhibits
metabolism - reduce dose of indinavir to 600 mg
every 8 hours.
Antimalarials: use artemether/lumefantrine with
caution; possibly increased quinine concentration.
Antipsychotics: possibly increased risk of ventricular
arrhythmias with pimozide - avoid; possibly inhibits
aripiprazole metabolism - reduce aripiprazole
dose; possibly increases lurasidone and quetiapine
concentration - avoid.
Antivirals: avoid with atazanavir; concentration
reduced by efavirenz, nevirapine and possibly
etravirine, avoid with etravirine; concentration of
both drugs increased with darunavir; concentration
of maraviroc increased, consider reducing maraviroc
dose; concentration increased by ritonavir; saquinavir
concentration increased.
Anxiolytics and hypnotics: increased risk of
prolonged sedation with alprazolam and midazolam
- avoid. Avanafil: concentration of avanafil possibly increased
- avoid.
Ciclosporin: concentration of ciclosporin increased.
Colchicine: possibly increases risk of colchicine
toxicity, avoid in hepatic or renal impairment.
Cytotoxics: possibly increases concentration of
axitinib, reduce dose of axitinib; possibly increases
bosutinib, cabazitaxel and docetaxel concentration
- avoid or reduce dose of bosutinib, cabazitaxel
and docetaxel; possibly increases concentration of
crizotinib and everolimus - avoid; possibly increases
ibrutinib concentration, reduce dose of ibrutinib;
avoid with olaparib and pazopanib; reduce dose of
ruxolitinib.
Ergot alkaloids: risk of ergotism - avoid.
Guanfacine: possibly increases guanfacine
concentration, halve dose of guanfacine.
5HT1 agonists: concentration of eletriptan increased
- avoid.
Lipid-regulating drugs: avoid with lomitapide
increased risk of myopathy with rosuvastatin and
simvastatin - avoid; and possibly with atorvastatin.
Naloxegol: possibly increases naloxegol concentration
- avoid.
Orlistat: absorption possibly reduced by orlistat.
Ranolazine: possibly increases ranolazine
concentration - avoid. Sildenafil: concentration of sildenafil increased -
reduce initial sildenafil dose.
Vardenafil: concentration of vardenafil increased -
avoid.
Metabolism
The usual oral dose for indinavir alone or in combination with other antiviral agents is one 800 mg capsule every 8 hours. The drug is well absorbed if given on an empty stomach or 1 hour before or 2 hours after a light meal with water. The dose is reduced to 600 mg every 8 hours if given concurrently with ketoconazole. Indinavir activity is increased when combined with RT inhibitors.
Check Digit Verification of cas no
The CAS Registry Mumber 150378-17-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,0,3,7 and 8 respectively; the second part has 2 digits, 1 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 150378-17:
(8*1)+(7*5)+(6*0)+(5*3)+(4*7)+(3*8)+(2*1)+(1*7)=119
119 % 10 = 9
So 150378-17-9 is a valid CAS Registry Number.
InChI:InChI=1/C36H47N5O4/c1-36(2,3)39-35(45)31-24-40(22-26-12-9-15-37-21-26)16-17-41(31)23-29(42)19-28(18-25-10-5-4-6-11-25)34(44)38-33-30-14-8-7-13-27(30)20-32(33)43/h4-15,21,28-29,31-33,42-43H,16-20,22-24H2,1-3H3,(H,38,44)(H,39,45)/t28-,29+,31+,32-,33+/m1/s1
150378-17-9Relevant articles and documents
Anti-HIV medicine containing indinavir and preparation method thereof
-
Paragraph 0017, (2018/08/28)
The invention discloses anti-HIV medicine containing indinavir and a preparation method thereof. The anti-HIV medicine containing indinavir is prepared from indinavir and pharmaceutically acceptable carriers, wherein the chemical name of indinavir is (1(1S,2R),5(S))-2,3,5-tri-deoxy-N-(2,3-dihydro-2-hydroxyl-1H-indene-1-yl)-5-[2-[[(1,1-dimethyl ethyl) amino]carbonyl]-4-(3-picolyl)-1-piperazinyl]-2-(benzyl)-D-erythro-valeramide. The process of a preparation process is simple and compact; the raw materials can be easily obtained; economic performance and environment protection are realized; the industrialization can be favorably realized; the economic technology development of the indinavir raw medicine of the anti-HIV medicine can be promoted; the dissolving-out degree of the anti-HIV medicine containing indinavir is high; the effect is ideal; the medicine is suitable for mass production.
Reductive alkylation of saturated cyclic amines
-
Page 17, (2008/06/13)
Saturated cyclic amines (e.g., piperazines and piperidines) are reductively alkylated with an N-containing heteroaryl carbaldehyde using an alkylcarboxylic acid and a borohydride to obtain a product comprising an N-((N-containing heteroaryl)methyl)-substituted cyclic amine and one or more borane complexes thereof, after which the product is treated with a catalytic amount of a Pt or Pd catalyst in the presence of an alcohol to cleave the borane complex(es) and thereby afford the N-((N-containing heteroaryl)methyl)cyclic amine free of borane complex. Saturated cyclic amines are also reductively alkylated by adding an N-containing heteroaryl carbaldehyde and the amine to a tetrahydroborate salt-alkylcarboxylic acid-solvent admixture and aging the resulting reaction mixture to obtain an alkylated product substantially free of borane complex.
Combinatorial diversification of indinavir: In vivo mixture dosing of an HIV protease inhibitor library
Rano, Thomas A.,Cheng, Yuan,Huening, Tracy T.,Zhang, Fengqi,Schleif, William A.,Gabryelski, Lori,Olsen, David B.,Kuo, Lawrence C.,Lin, Jiunn H.,Xu, Xin,Olah, Timothy V.,McLoughlin, Debra A.,King, Richard,Chapman, Kevin T.,Tata, James R.
, p. 1527 - 1530 (2007/10/03)
An efficient combination solution-phase/solid-phase route enabling the diversification of the P1', P2', and P3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates. (C) 2000 Elsevier Science Ltd. All rights reserved.