公开(公告)号：US20230149342A1

公开(公告)日：2023-05-18

申请号：US17522866

申请日：2021-11-09

申请人： KYLE OLSON ,  HAROLD MECKLER ,  MARCUS BRACKEEN ,  MARIO TREMBLAY

发明人： KYLE OLSON ,  HAROLD MECKLER ,  MARCUS BRACKEEN ,  MARIO TREMBLAY

IPC分类号： A61K31/352 ,  C07C37/74 ,  C07D311/78 ,  A61K31/05 ,  B01J31/14 ,  B01D3/10 ,  B01D1/08 ,  B01D3/14 ,  B01D11/04 ,  B01D39/20 ,  A23L33/105

CPC分类号： A61K31/352 ,  C07C37/74 ,  C07D311/78 ,  A61K31/05 ,  B01J31/143 ,  B01D3/10 ,  B01D1/08 ,  B01D3/143 ,  B01D11/0492 ,  B01D39/2068 ,  A23L33/105 ,  A61K2236/55 ,  B01D2011/002

摘要： The present invention describes a method which outlines a process for conversion of CBD to a Δ9-tetrahydrocannabinol (Δ9-THC) compound or derivative thereof involving treating a naturally produced CBD intermediate compound with an organoaluminum-based Lewis acid catalyst, under conditions effective to produce the Δ9-tetrahydrocannabinol compound or derivative thereof at a relatively high concentration. The source of the CBD is from industrial hemp having less than 0.3% Δ9-THC and extracting and purifying a CBD distillate or isolate or a combination thereof. This procedure will produce Δ9-THC that is essentially free from any other cannabinoids other than some trace amounts of the initial CBD starting material, or about 95% Δ9-THC and 2-4% CBD. Another aspect of the present invention relates to a process for further purification and enrichment of the Δ9-THC using distillation and collecting an essentially pure fraction of Δ9-THC using additional distillation or enrichment form of purification. Included are methods and processes to scale the reaction from the lab to large scale manufacturing. Included are methods for adding a molecule marker to authenticate high purity Δ9-THC products. Formulations and uses for pharmaceuticals, nutraceuticals, food products, and topicals are also provided.

公开(公告)号：US4952694A

公开(公告)日：1990-08-28

申请号：US224966

申请日：1988-07-27

申请人： Marcus Brackeen ,  Harry R. Howard, Jr.

发明人： Marcus Brackeen ,  Harry R. Howard, Jr.

IPC分类号： A61K31/35 ,  A61K31/38 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/4188 ,  A61P3/10 ,  C07D233/72 ,  C07D235/02 ,  C07D471/10 ,  C07D471/20 ,  C07D491/10 ,  C07D491/107 ,  C07D491/20 ,  C07D495/10 ,  C07D495/20

CPC分类号： C07D471/10 ,  C07D491/10

摘要： A novel three-step process for resolving a racemic spiro-hydantoin compound into its optical antipodes is disclosed, which involves (1) reacting said racemic compound with an optically-active asymmetric isocyanate of the formula RNCO, wherein R is (S)- or (R)-1-phenylethyl or (S) or (R)-1-(1-naphthyl)ethyl, to form the corresponding diastereomeric uredio compound; (2) separating the resulting diastereomeric mixture into its component parts, and (3) thereafter converting the separated ureido diastereomers obtained in step (b) to the corresponding asymmetric hydantoin compounds by treatment with an alkali metal lower alkoxide (C.sub.1 -C.sub.4), followed by acidification, whereupon the desired optical isomer is obtained. The final products so obtained, such as (4S)-(+)-6-fluoro-2,3-dihydro-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2', 5'-dione (sorbinil) and (5'S)-3'-chloro-5', 6', 7', 8'-tetra-hydro-spiro[imidazolidine-4,5'-quinoline]-2,5-dione, are known to be useful in preventing or alleviating certain chronic diabetic complications. The aforementioned diastereomeric uredio intermediates are novel compounds.

公开(公告)号：US5859007A

公开(公告)日：1999-01-12

申请号：US722051

申请日：1996-11-14

申请人： Christopher Joseph Aquino ,  Marcus Brackeen ,  Milana Dezube ,  Brad Richard Henke ,  Gavin Charles Hirst ,  Peter Walter Jeffs ,  Tanya Momtahen ,  Elizabeth Ellen Sugg ,  Edward Martin Suh ,  Timothy Mark Willson

发明人： Christopher Joseph Aquino ,  Marcus Brackeen ,  Milana Dezube ,  Brad Richard Henke ,  Gavin Charles Hirst ,  Peter Walter Jeffs ,  Tanya Momtahen ,  Elizabeth Ellen Sugg ,  Edward Martin Suh ,  Timothy Mark Willson

IPC分类号： A61K31/55 ,  A61P1/00 ,  A61P1/16 ,  A61P3/04 ,  C07D243/12 ,  C07D401/04 ,  C07D401/14 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D471/04 ,  C07D498/04 ,  A01N43/62

CPC分类号： C07D401/04 ,  C07D243/12 ,  C07D401/14 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D471/04

摘要： Benzo�b!�1,4!diazepine compounds of formula (I), where R.sup.1 is selected from C.sub.1 C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl, or substituted phenyl; R.sup.2 is selected from C.sub.3 -C.sub.6 alkyl, C.sub.3 C.sub.6 cycloalkyl, C.sub.3 -C.sub.6 alkenyl, benzyl, phenylC.sub.1 -C.sub.3 alkyl of substituted phenyl; or NR.sup.1 R.sup.2 together form 1,2,3,4-tetrahydroquinoline or benzazepine, mono-, di-, or trisubstituted independently with C.sub.1-6 alkyl C.sub.1-6 alkoxy or halogen substituents; p is an integer 0 or 1; q is an integer 0 or 1; r is an integer 0 or 1; t is an integer 0 or 1, provided that when r is 0 then t is 0; R.sup.3, R.sup.5, and R.sup.6 are independently hydrogen or C.sub.1-6 alkyl; R.sup.4 is C.sub.1-6 alkyl or C.sub.1-6 alkenyl; R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 cycloalkyl, C.sub.1-6 alkenyl, phenyl, substituted phenyl, napthyl, heteroaryl, substituted heteroaryl, bicycloheteroaryl or substituted bicycloheteroaryl; or NR.sup.6 R.sup.7 together form a saturated 5,6, or 7 membered ring optionally interrupted by 1,2,3 or 4 N, S or O heteroatoms, with the proviso that any two O or S atoms are not bonded to each other, m is an integer selected from the group of 0, 1, 2, 3 or 4; R.sup.8 and R.sup.9 are selected from a variety of substituents; Z is hydrogen or halogen; novel intermediates, a pharmaceutical composition for treating obesity, gall bladder stasis, disorders of pancreatic secretion, methods for such treatment and processes for preparing compounds of formula (I).

摘要翻译： PCT No.PCT / EP95 / 01336 Sec。 371日期：1996年11月14日 102（e）1996年11月14日PCT PCT 1995年4月13日PCT公布。 公开号WO95 / 28391 日期：1995年10月26日（I）式（I）的苯并[b] [1,4]二氮杂化合物，其中R 1选自C 1 -C 6烷基，C 3 -C 6环烷基，苯基或取代的苯基; R2选自C3-C6烷基，C3C6环烷基，C3-C6链烯基，苄基，取代苯基的苯基C1-3烷基; 或NR1R2一起形成1,2,3,4-四氢喹啉或苯并氮杂，独立地与C 1-6烷基C 1-6烷氧基或卤素取代基单取代，二取代或三取代; p是整数0或1; q是整数0或1; r为整数0或1; t为整数0或1，条件是当r为0时，t为0; R3，R5和R6独立地是氢或C1-6烷基; R4是C1-6烷基或C1-6链烯基; R 7选自氢，C 1-6烷基，C 1-6环烷基，C 1-6烯基，苯基，取代的苯基，萘基，杂芳基，取代的杂芳基，双环杂芳基或取代的双环杂芳基; 或NR6R7一起形成饱和的5,6或7元环，任选地被1,2,3或4个N，S或O杂原子间隔，条件是任何两个O或S原子彼此不结合，m是 选自0,1,2,3或4的整数; R8和R9选自多种取代基; Z是氢或卤素; 新型中间体，用于治疗肥胖的药物组合物，胆囊淤滞，胰腺分泌障碍，这种治疗方法和制备式（I）化合物的方法。

公开(公告)号：US5006657A

公开(公告)日：1991-04-09

申请号：US543986

申请日：1990-06-25

申请人： Marcus Brackeen ,  Harry R. Howard, Jr.

发明人： Marcus Brackeen ,  Harry R. Howard, Jr.

IPC分类号： C07D471/10 ,  C07D491/10

CPC分类号： C07D471/10 ,  C07D491/10

摘要： A novel three-step process for resolving a racemic spiro-hydantoin compound into its optical antipodes is disclosed, which involves (1) reacting said racemic compound with an optically-active asymmetric isocyanate of the formula RNCO, wherein R is (S)- or (R)-1-phenylethyl or (S)-or (R)-1-(1-naphthyl)ethyl, to form the corresponding diastereomeric ureido compound; (2) separating the resulting diastereomeric mixture into its component parts, and (3) thereafter converting the separated ureido diasteromers obtained in step (b) to the corresponding asymmetric hydantoin compounds by treatment with an alkali metal lower alkoxide (C.sub.1 -C.sub.4), followed by acidification, whereupon the desired optical isomer is obtained. The final products so obtained, such as (4S)-(+)-6-fluoro-2,3-dihydro-spiro-[4H-1-benzopyran-4,4'-imidazolidine]-2',5'-dione(sorbinil) and (5'S)-3'-chloro-5', 6',7',8'-tetrahydro-spiro[imidazolidine-4,5'-quinoline]-2,5-dione, are known to be useful in preventing or alleviating certain chronic diabetic complications. The aforementioned diastereomeric ureido intermediates are novel compounds.

摘要翻译： 公开了一种用于将外消旋螺 - 乙内酰脲化合物分解成其光学对映体的新型三步法，其包括（1）使所述外消旋化合物与式RNCO的光学活性不对称异氰酸酯反应，其中R是（S） - 或 （R）-1-苯乙基或（S） - 或（R）-1-（1-萘基）乙基，形成相应的非对映异构脲基化合物; （2）将得到的非对映异构体混合物分离成其组分，（3）此后通过用碱金属低级醇盐（C1-C4）处理将步骤（b）中得到的分离的脲基非对映异构体转化成相应的不对称乙内酰脲化合物，随后 通过酸化，得到所需的旋光异构体。 得到的最终产物如（4S） - （+） - 6-氟-2,3-二氢 - 螺 - [4H-1-苯并吡喃-4,4'-咪唑烷e] -2' 二酮（sorbinil）和（5'S）-3'-氯-5'，6'，7'，8'-四氢 - 螺[咪唑烷-4,5'-喹啉] -2,5-二酮已知为 可用于预防或减轻某些慢性糖尿病并发症。 上述非对映异构体脲基中间体是新化合物。

公开(公告)号：US06294580B1

公开(公告)日：2001-09-25

申请号：US09125750

申请日：1998-08-25

申请人： Timothy Mark Willson ,  Robert Anthony Mook ,  Istvan Kaldor ,  Brad Richard Henke ,  David Norman Deaton ,  Jon Loren Collins ,  Jeffrey Edmond Cobb ,  Marcus Brackeen ,  Matthew Jude Sharp ,  John Mark O'Callaghan ,  Greg Alan Erickson ,  Grady Evan Boswell

发明人： Timothy Mark Willson ,  Robert Anthony Mook ,  Istvan Kaldor ,  Brad Richard Henke ,  David Norman Deaton ,  Jon Loren Collins ,  Jeffrey Edmond Cobb ,  Marcus Brackeen ,  Matthew Jude Sharp ,  John Mark O'Callaghan ,  Greg Alan Erickson ,  Grady Evan Boswell

IPC分类号： A61K3119

CPC分类号： C07D213/64 ,  A61K31/192 ,  A61K31/216 ,  A61K31/353 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/42 ,  A61K31/422 ,  A61K31/423 ,  A61K31/425 ,  A61K31/427 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4439 ,  A61K31/4453 ,  A61K31/454 ,  A61K31/495 ,  C07C229/36 ,  C07C229/56 ,  C07C237/40 ,  C07C255/54 ,  C07C323/12 ,  C07C2601/14 ,  C07C2601/16 ,  C07D207/08 ,  C07D213/65 ,  C07D213/70 ,  C07D213/74 ,  C07D231/12 ,  C07D233/64 ,  C07D235/12 ,  C07D237/14 ,  C07D249/08 ,  C07D261/08 ,  C07D263/32 ,  C07D263/56 ,  C07D277/24 ,  C07D277/42 ,  C07D311/22 ,  C07D333/36 ,  C07D401/04 ,  C07D405/04 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04

摘要： A compound having formula (I), wherein A is selected from the group consisting of: (i) phenyl, wherein said phenyl is optionally substituted by one or more halogen atoms, C1-6alkyl, C1-3alkoxy, C1-3fluoroalkoxy, nitrile, or —NR7R8 where R7 and R8 are independently hydrogen or C1-3alkyl; (ii) a 5- or 6-membered hetrocyclic group containing at least one heteroatom selected from oxygen, nitrogen and sulfur; and (iii) a fused bicyclic ring (a), wherein ring C represents a heterocyclic group as defined in point (ii) above, which bicyclic ring is attached to group B via a ring atom of ring C; B is selected from the group consisting of: (iv) C1-6alkylene; (v) —MC1-6alkylene or C1-6alkyleneMC1-6alkylene, wherein M is O, S, or —NR2 wherein R2 represents hydrogen or C1-3alkyl; (vi) a 5- or 6-membered heterocyclic group containing at least one nitrogen heteroatom and optionally at least one further heteroatom selected from oxygen, nitrogen and sulfur and optionally substituted by C1-3alkyl; and (vii) Het-C1-6alkylene, wherein Het represents a heterocyclic group as defined in point (vi) above; Alk represents C1-3alkylene; R1 represents hydrogen or C1-3alkyl; Z is selected from the group consisting of: (viii) —(C1-3alkylene) phenyl, which phenyl is optionally substituted by one or more halogen atoms; and (ix) —NR3R4, wherein R3 represents hydrogen or C1-3alkyl, and R4 represents —Y—(C═O)—T—R5, or —Y—(CH(OH))—T—R5.

摘要翻译： 具有式（I）的化合物，其中A选自：（i）苯基，其中所述苯基任选被一个或多个卤素原子取代，C 1-6烷基，C 1-3烷氧基，C 1-3氟烷氧基，腈， 或-NR 7 R 8，其中R 7和R 8独立地是氢或C 1-3烷基; （ii）含有至少一个选自氧，氮和硫的杂原子的5-或6-元环庚基; 和（iii）稠合双环（a），其中环C表示如上述点（ii）中所定义的杂环基，该双环通过环C的环原子连接至基团B; B选自：（iv）C 1-6亚烷基; （v）-MC1-6亚烷基或C 1-6亚烷基基团，C 1-6亚烷基，其中M为O，S或-NR 2，其中R 2表示氢或C 1-3烷基; （vi）含有至少一个氮杂原子和任选至少一个选自氧，氮和硫的另外的杂原子并任选被C 1-3烷基取代的5-或6-元杂环基; 和（vii）Het-C 1-6亚烷基，其中Het表示如上述（vi）中所定义的杂环基; Alk表示C1-3亚烷基; R1代表氢或C1-3烷基; Z选自：（ii） - （C 1-3亚烷基）苯基，该苯基任选被一个或多个卤素原子取代; 和（ix）-NR3R4，其中R3表示氢或C1-3烷基，R4表示-Y-（C = O）-T-R5或-Y-（CH（OH））-T-R5。