CA2647316C - Process for preparation of hiv protease inhibitors - Google Patents

Process for preparation of hiv protease inhibitors Download PDF

Info

Publication number
CA2647316C
CA2647316C CA2647316A CA2647316A CA2647316C CA 2647316 C CA2647316 C CA 2647316C CA 2647316 A CA2647316 A CA 2647316A CA 2647316 A CA2647316 A CA 2647316A CA 2647316 C CA2647316 C CA 2647316C
Authority
CA
Canada
Prior art keywords
formula
compound
combining
acid
mixture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CA2647316A
Other languages
English (en)
French (fr)
Other versions
CA2647316A1 (en
Inventor
Kenneth R. Crawford
Eric D. Dowdy
Arnold Gutierrez
Richard P. Polniaszek
Richard Hung Chiu Yu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gilead Sciences Inc
Original Assignee
Gilead Sciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of CA2647316A1 publication Critical patent/CA2647316A1/en
Application granted granted Critical
Publication of CA2647316C publication Critical patent/CA2647316C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/38—Amides of thiocarboxylic acids
    • C07C327/40—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C327/42—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4075—Esters with hydroxyalkyl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4084—Esters with hydroxyaryl compounds

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Engineering & Computer Science (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Epidemiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CA2647316A 2006-03-29 2007-03-29 Process for preparation of hiv protease inhibitors Active CA2647316C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US78712606P 2006-03-29 2006-03-29
US60/787,126 2006-03-29
PCT/US2007/007564 WO2007126812A2 (en) 2006-03-29 2007-03-29 Process for preparation of hiv protease inhibitors

Publications (2)

Publication Number Publication Date
CA2647316A1 CA2647316A1 (en) 2007-11-08
CA2647316C true CA2647316C (en) 2013-05-28

Family

ID=38323963

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2647316A Active CA2647316C (en) 2006-03-29 2007-03-29 Process for preparation of hiv protease inhibitors

Country Status (24)

Country Link
US (4) US20110065631A1 (enExample)
EP (2) EP2570416B1 (enExample)
JP (2) JP5430395B2 (enExample)
KR (2) KR101429300B1 (enExample)
CN (2) CN102516259B (enExample)
AP (2) AP2013006690A0 (enExample)
AU (1) AU2007245194B2 (enExample)
BR (1) BRPI0710199A2 (enExample)
CA (1) CA2647316C (enExample)
DK (1) DK1999133T3 (enExample)
EA (2) EA016140B1 (enExample)
ES (2) ES2572001T3 (enExample)
HR (2) HRP20140626A2 (enExample)
IL (2) IL194122A (enExample)
MX (1) MX2008012398A (enExample)
NO (2) NO342102B1 (enExample)
NZ (2) NZ596074A (enExample)
PL (1) PL1999133T3 (enExample)
PT (1) PT1999133E (enExample)
SG (1) SG170794A1 (enExample)
SI (1) SI1999133T1 (enExample)
UA (1) UA97241C2 (enExample)
WO (1) WO2007126812A2 (enExample)
ZA (1) ZA200808046B (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015123282A1 (en) * 2014-02-12 2015-08-20 Fotsing Joseph R Improved process for the synthesis of substituted 1-benzyl-3-(1-(isoxazol-4-ylmethyl)-1h-pyrazol-4-yl)imidazolidine-2,4-diones

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8921415B2 (en) 2009-01-29 2014-12-30 Mapi Pharma Ltd. Polymorphs of darunavir
PL2528923T3 (pl) 2010-01-28 2015-01-30 Mapi Pharma Ltd Sposób wytwarzania darunawiru i pochodnych darunawiru
CN102190638A (zh) * 2010-03-16 2011-09-21 中国科学院上海药物研究所 联芳基醇二胺类化合物、其药物组合物、制备方法及应用
CN102584748B (zh) * 2011-01-13 2015-02-11 浙江九洲药业股份有限公司 夫沙那韦中间体的制备方法
EP2702045B1 (en) * 2011-04-26 2017-10-18 Mylan Laboratories Ltd. Novel process for the preparation of etravirine
ES2661705T3 (es) 2011-10-07 2018-04-03 Gilead Sciences, Inc. Métodos para la preparación de análogos de nucleótidos antivirales
EP2634180A1 (en) 2012-03-01 2013-09-04 Lonza Ltd. Enzymatic process for the preparation of butyrolactones
CN103664976B (zh) * 2013-12-12 2015-11-04 惠州市莱佛士制药技术有限公司 一种顺式六氢呋喃并[2,3-b]呋喃-3-醇的制备方法
WO2016106050A1 (en) 2014-12-26 2016-06-30 Emory University N4-hydroxycytidine and derivatives and anti-viral uses related thereto
JP6435907B2 (ja) * 2015-02-16 2018-12-12 住友化学株式会社 ヘキサヒドロフロフラノール誘導体の製造方法
CN108610227B (zh) * 2016-12-10 2021-02-09 中国科学院大连化学物理研究所 一种制备双环芳香化合物的方法
RU2020116571A (ru) 2017-12-07 2021-11-22 Эмори Юниверсити N4-гидроксицитидин и производные и связанные с этим противовирусные применения
MX2021008751A (es) 2019-01-25 2021-11-12 Univ Brown Composiciones y metodos para tratar, prevenir o revertir la inflamacion y los trastornos asociados a la edad.

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994026749A1 (en) * 1993-05-14 1994-11-24 Merck & Co., Inc. Hiv protease inhibitors
AU1369001A (en) * 1995-12-13 2001-03-22 Abbott Laboratories Retroviral protease inhibiting compounds
ATE401298T1 (de) 1999-12-23 2008-08-15 Ampac Fine Chemicals Llc Verbessertes verfahren zur herstellung von 2s,3s- n-isobutyl-n-(2-hydroxy-3-amino-4-phenylbutyl)- - nitrobenzenesulfonylamid hydrochlorid und anderen derivaten von 2-hydroxy-1,3-diamin
WO2002060905A2 (en) * 2000-10-24 2002-08-08 Glaxo Group Ltd Process for preparing intermediates of hiv protease inhibitors
EP1436884A2 (en) 2001-07-20 2004-07-14 Koninklijke Philips Electronics N.V. Oscillating circuit, converter with such oscillating circuit, and preconditioner with such converter
TW200408645A (en) * 2002-04-26 2004-06-01 Gilead Sciences Inc Non nucleoside reverse transcriptase inhibitors
US20050239054A1 (en) * 2002-04-26 2005-10-27 Arimilli Murty N Method and compositions for identifying anti-HIV therapeutic compounds
WO2005042773A1 (en) * 2003-10-24 2005-05-12 Gilead Sciences, Inc. Methods and compositions for identifying therapeutic compounds

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015123282A1 (en) * 2014-02-12 2015-08-20 Fotsing Joseph R Improved process for the synthesis of substituted 1-benzyl-3-(1-(isoxazol-4-ylmethyl)-1h-pyrazol-4-yl)imidazolidine-2,4-diones

Also Published As

Publication number Publication date
US20130172295A1 (en) 2013-07-04
US20120258935A1 (en) 2012-10-11
AU2007245194B2 (en) 2013-03-14
DK1999133T3 (da) 2013-11-25
UA97241C2 (uk) 2012-01-25
EA201100994A1 (ru) 2012-03-30
EP1999133B1 (en) 2013-08-21
AP2757A (en) 2013-09-30
NO342102B1 (no) 2018-03-26
JP5430395B2 (ja) 2014-02-26
CA2647316A1 (en) 2007-11-08
WO2007126812A3 (en) 2007-12-21
BRPI0710199A2 (pt) 2012-03-06
US8431745B2 (en) 2013-04-30
KR101395377B1 (ko) 2014-05-14
HRP20080554B1 (hr) 2014-11-21
EA020088B1 (ru) 2014-08-29
EA016140B1 (ru) 2012-02-28
SG170794A1 (en) 2011-05-30
ES2572001T3 (es) 2016-05-27
CN101448838B (zh) 2012-07-04
KR20080108322A (ko) 2008-12-12
KR101429300B1 (ko) 2014-08-11
NZ571302A (en) 2011-11-25
PL1999133T3 (pl) 2014-01-31
EA200802074A1 (ru) 2009-02-27
US8173623B2 (en) 2012-05-08
CN101448838A (zh) 2009-06-03
KR20140021047A (ko) 2014-02-19
NZ596074A (en) 2013-03-28
NO20180086A1 (no) 2008-12-22
ZA200808046B (en) 2009-06-24
CN102516259A (zh) 2012-06-27
EP2570416A1 (en) 2013-03-20
NO20084547L (no) 2008-12-22
EP2570416B1 (en) 2016-03-16
JP2013082717A (ja) 2013-05-09
CN102516259B (zh) 2014-12-10
AP2008004641A0 (en) 2008-10-31
US20080004242A1 (en) 2008-01-03
US20110065631A1 (en) 2011-03-17
HK1126756A1 (en) 2009-09-11
SI1999133T1 (sl) 2013-10-30
WO2007126812A2 (en) 2007-11-08
HRP20080554A2 (hr) 2009-02-28
JP2009531441A (ja) 2009-09-03
PT1999133E (pt) 2013-10-16
ES2430557T3 (es) 2013-11-21
NO342965B1 (no) 2018-09-10
EP1999133A2 (en) 2008-12-10
IL225167A (en) 2016-03-31
HK1180311A1 (en) 2013-10-18
AP2013006690A0 (en) 2013-01-31
HRP20140626A2 (hr) 2014-11-07
AU2007245194A1 (en) 2007-11-08
IL194122A (en) 2016-08-31
MX2008012398A (es) 2008-12-17

Similar Documents

Publication Publication Date Title
EP1999133B1 (en) Process for preparation of hiv protease inhibitors
KR20210032950A (ko) 페닐피페리디닐 인돌 유도체를 제조하기 위한 화학적 방법
CN107540574B (zh) R-联苯丙氨醇的制备方法
KR101832238B1 (ko) 신규한 설포닐옥시메틸포스포네이트 유도체 및 이를 이용한 다이아이소프로필 ((1-(트리틸옥시메틸)-사이클로프로필)옥시)메틸 포스포네이트의 제조방법
HK1126756B (en) Process for preparation of hiv protease inhibitors
HK1180311B (en) Antiviral bisfuran derivative as hiv protease inhibitor and intermediates thereof
CN117186100B (zh) 一种乙烯基环丙烷核苷类似物的制备方法
CN109641863A (zh) (s)-2-氨基-4-甲基-1-((r)-2-甲基环氧乙烷-2-基)-戊-1-酮及其药学上可接受的盐的合成
AU2024326972A1 (en) Linker-drug compounds and methods of making thereof
JP2008007457A (ja) β−ヒドロキシカルボニル化合物の後処理方法

Legal Events

Date Code Title Description
EEER Examination request
MPN Maintenance fee for patent paid

Free format text: FEE DESCRIPTION TEXT: MF (PATENT, 18TH ANNIV.) - STANDARD

Year of fee payment: 18

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20241223

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT DETERMINED COMPLIANT

Effective date: 20241223

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20241223

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-4-4-W10-W00-W100 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: LETTER SENT

Effective date: 20260511